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  • 1.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Katajamaa, Rebecca
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus)2015In: Biology Letters, ISSN 1744-9561, E-ISSN 1744-957X, Vol. 11, no 9, article id 20150509Article in journal (Refereed)
    Abstract [en]

    Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44-48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low-fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication.

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  • 2.
    Altimiras, Jordi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Axelsson, Michael
    Department of Zoology University of Göteborg.
    Intrinsic autoregulation of cardiac output in rainbow trout (Oncorhynchus mykiss) at different heart rates2004In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 207, p. 195-201Article in journal (Refereed)
  • 3.
    Altimiras, Jordi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Claireaux, G.
    Sandblom, E.
    Farrell, A.P.
    McKenzie, D.J.
    Axelsson, M.
    Gastrointestinal blood flow and postprandial metabolism in swimming sea bass dicentrarchus labrax2008In: Physiological and Biochemical Zoology, ISSN 1522-2152, E-ISSN 1537-5293, Vol. 81, no 5, p. 663-672Article in journal (Refereed)
    Abstract [en]

    In trout and salmon, the metabolic costs of exercise and feeding are additive, which would suggest that gastrointestinal blood flow during exercise is maintained to preserve digestive and absorptive processes related to the specific dynamic action (SDA) of food. However, in most published studies, gastrointestinal blood flow drops during swimming, hypoxia, and general stress. To test whether gastrointestinal blood flow is spared during exercise after feeding, sea bass were instrumented with flow probes to measure cardiac output and celiacomesenteric blood flow while swimming in a respirometer before and after feeding. Swimming at 2 body lengths per second (bl s-1) increased metabolic rate considerably more than did feeding (208% vs. 32% increase, respectively, relative to resting), and a similar pattern was observed for cardiac output. In unfed fish, resting gastrointestinal blood flow was mL 13.8 ± 0.5 min-1 kg-1. After feeding, resting gastrointestinal blood flow increased by 82% but then decreased progressively with increasing swimming speeds. At 2 bl s-1, gastrointestinal blood flow in fed fish was not significantly different compared with that in unfed swimming fish, and, therefore, the data do not support the gastrointestinal sparing hypothesis. The magnitude of the SDA was maintained despite the decrease in gastrointestinal blood flow and the consequent reduction in oxygen supply to the gut. An estimate of maximal oxygen flow to the gastrointestinal tract after feeding yielded 2.6 mmol O2 h-1 kg-1, but this amount is not able to cover the oxygen demand of 3.16 mmol O2 h -1 kg-1. Therefore, the SDA must reflect metabolic processes in tissues other than those directly perfused by the celiacomesenteric artery. © 2008 by The University of Chicago. All rights reserved.

  • 4.
    Altimiras, Jordi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Crossley II, D.
    n/a.
    Villamor, E.
    n/a.
    Prenatal development of cardiovascular regulation in avian species.2009In: Cardio-respiratory control in vertebrates: comparative and evolutionary aspects, Dordrecht Heidelberg London New York: Springer , 2009, 1, p. 397-427Chapter in book (Other academic)
    Abstract [en]

    The focus of this book is the evolution of cardiovascular and respiratory control in vertebrates. Life originated in water, which has constantly changing temperatures and O2 levels. Fish gills can extract up to 80% of their inspired O2, because they have a countercurrent bloodstream. Oxygen sensors have been found within the gill arches of ray-finned fish such as carp and trout, and these O2 sensors screen the inspired water and the capillary blood. Very likely, land vertebrates and the lungfish arose as a sister group, and both possess real lungs. Lungfish include 6 species, inhabiting shallow lakes or rivers, whereas the second ramification includes all the land vertebrates. A possible ancestor to the lungfish and land vertebrates has been discovered in China, and this fossil (Styloichthys) bridges a gap. Living 417 million years ago, it could represent one of the last ramifications before the common ancestor to the lungfish and land vertebrates. In addition, rather constant atmospheric O2 levels permit a joint acid-base regulation by the lung and the kidney. Likewise, lungfish and land vertebrates share a central control of pulmonary ventilation, while the peripheral receptor contribution to acid-base regulation is minor

  • 5.
    Altimiras, Jordi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Gräns, Albin
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Ontogeny of vocalizations and movements in response to cooling in chickens fetuses2007In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 91, p. 229-239Article in journal (Refereed)
  • 6.
    Altimiras, Jordi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Milberg, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Ecology .
    Letter regarding article by Kahn et al. "Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring" (Adaption is not predictive)2005In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 111, p. 166-166Article in journal (Other academic)
  • 7.
    Bagatto, B.
    et al.
    University of Akron, USA.
    Crossley II, D. .
    University of North Texas, Denton, USA.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Elsey, R. M.
    Rockefeller Wildlife Refuge, Lousiana Department of Wildlife and Fisheries, Grand Chenier, LA, USA.
    Hicks, J. W.
    University of California at Irvine, USA.
    Physiological variability in yearling alligators: Clutch differences at rest andduring activity2012In: Comparative Biochemistry and Physiology - Part A: Comparative Physiology, ISSN 0300-9629, Vol. Part A, no 162, p. 44-50Article in journal (Refereed)
    Abstract [en]

    The adult phenotype of an organism is the result of its genotype, the environment, and the interaction betweenthe two. Assessing the relative contribution of these factors to the final adult phenotype continues tooccupy researchers. Studies have shown clutch effects early in development but few have investigated thepersistence of clutch effects on a longer time scale. Five clutches of American alligators were reared for1 year in a common environment then assessed for the presence of clutch effects as they related to morphologicaland physiological characteristics. After 1 year, significant clutch effects were evident in all size relatedvariables despite open access to food. Additionally, lung and liver masses remained different betweenclutches after animal mass was taken into account. Although clutch had no effect on resting heart rate, itsignificantly contributed to mean arterial pressure. During swimming and exhaustive exercise, the resultingrespiratory and metabolic acidoses were strongly dependent on clutch. Therefore, while the environmentcan have significant influences on the American alligator from hatching to death, the measureable contributionof genetics to the morphology and physiology of the organism remains evident, even after 1 year ofcommon rearing conditions. It behooves researchers to acknowledge and control for clutch effects when designingexperiments.

  • 8.
    Crossley, D A
    et al.
    University of N Texas, TX 76203 USA .
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Effect of selection for commercially productive traits on the plasticity of cardiovascular regulation in chicken breeds during embryonic development2012In: Poultry Science, ISSN 0032-5791, E-ISSN 1525-3171, Vol. 91, no 10, p. 2628-2636Article in journal (Refereed)
    Abstract [en]

    Domesticated animal breeds have experienced profound anatomical and physiological changes as a result of human-driven genetic selection. In poultry, this selection process has resulted in many distinct phenotypes from the ancestral bird, the Red Jungle-fowl. Growth rate and egg-laying capacity are 2 traits that have been commercially prioritized, and this has resulted in a fast-growth breed, the broiler, and a prolific egg layer, the White Leghorn. In this study, we investigated basic cardiovascular physiology in these 3 breeds at 90% of incubation. We aimed to identify breed-specific features of arterial blood pressure and heart rate as well as the physiological mechanisms regulating them. Specifically, we investigated mechanisms mediated by the autonomic nervous system by means of cholinergic and adrenergic receptors. Our overriding hypothesis was that selection for rapid growth would require an acceleration of heart rate and arterial pressure development in broilers compared with White Leghorns and the ancestral breed. The embryonic broiler is characterized by resting relative hypertensive bradycardia, whereas the White Leghorn is hypotensive. All 3 breeds maintained resting arterial pressure and heart rate via a similar beta- arid alpha-adrenergic receptor tone; however, cholinergic tone on heart rate was absent in the embryonic White Leghorn. Each breed responded differently to incubation in chronic hypoxic conditions (14% O-2). White Leghorn relied on augmenting cholinergic heart rate tone, and broilers relied on reducing beta-adrenergic tone on pressure. We concluded that selection for rapid growth shifts cardiovascular regulatory plasticity to emphasize mechanisms that modulate pressure, and that selection for egg-laying capacity emphasizes mechanisms that modulate heart rate.

  • 9.
    Crossley, DA
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Burggren, WW
    Altimiras, Jordi
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Zoology .
    Cardiovascular regulation during hypoxia in embryos of the domestic chicken Gallus gallus2003In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 284, no 1, p. R219-R226Article in journal (Refereed)
    Abstract [en]

    Renewed interest in the use of the embryonic chicken as a model of perinatal cardiovascular regulation has inspired new questions about the control mechanisms that respond to acute perturbations, such as hypoxia. The objectives of this study were to determine the cardiovascular responses, the regulatory mechanisms involved in those cardiovascular responses, and whether those mechanisms involved the central nervous system (CNS) of embryonic chickens. Heart rate (f(H)) and blood pressure were measured in chicken embryos of different incubation ages during exposure to different levels of hypoxia (15, 10, and 5% O-2). At all levels of hypoxia and at all developmental ages, a depression of fH and arterial pressure was observed, with the exception of day 20 embryos in 15 and 10% O2. The intensity of the embryonic fH and blood pressure responses were directly related to the level of hypoxia used. Muscarinic and alpha-adrenergic receptor stimulation limited the hypoxic hypotension on days 15-19 and 15-21, respectively, as indicated after blockade with atropine and phentolamine. During the final 3 days of incubation, the intensity of the hypoxic hypotension was magnified due to alpha-vasodilation caused by beta-adrenergic and muscarinic receptor stimulation. In 19- to 21-day-old embryos, the fH response to hypoxia was limited by alpha-adrenergic receptor stimulation as indicated by the accentuated bradycardia after blockade with phentolamine. Furthermore, on day 21, atropine limited the hypoxic bradycardia, indicating that muscarinic receptors also play a role in the fH response at this age. In addition, the muscarinic actions on the heart and the adrenergic effects on the vasculature appeared to occur through a hypoxic-induced direct release from chromaffin tissue and autonomic nerve terminals. Thus, in embryonic chickens, the only cardiovascular response to hypoxia that involves the CNS was the cholinergic regulation of arterial pressure after day 15 of incubation. Therefore, although embryonic chickens and fetal sheep, the standard models of perinatal cardiovascular physiology, respond to hypoxia with a similar redistribution of cardiac output, the underlying mechanisms differ between these species.

  • 10.
    Crossley II, Dane A.
    et al.
    University of California Irvine, USA.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Cardiovascular development in embryos of the American alligator Alligator mississippiensis: effects of chronic and acute hypoxia2005In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 208, p. 31-39Article in journal (Refereed)
    Abstract [en]

    Chronic hypoxic incubation is a common tool used to address the plasticity of morphological and physiological characteristics during vertebrate development. In this study chronic hypoxic incubation of embryonic American alligators resulted in both morphological (mass) and physiological changes. During normoxic incubation embryonic mass, liver mass and heart mass increased throughout the period of study, while yolk mass fell. Chronic hypoxia (10%O2) resulted in a reduced embryonic mass at 80% and 90% of incubation. This reduction in embryonic mass was accompanied by a relative enlargement of the heart at 80% and 90% of incubation, while relative embryonic liver mass was similar to the normoxic group. Normoxic incubated alligators maintained a constant heart rate during the period of study, while mean arterial pressure rose continuously. Both levels of hypoxic incubation (15% and 10%O2) resulted in a lower mean arterial pressure at 90% of incubation, while heart rate was lower in the 10%O2 group only. Acute (5 min) exposure to 10%O2 in the normoxic group resulted in a biphasic response, with a normotensive bradycardia occurring during the period of exposure and a hypertensive tachycardic response occurring during recovery. The embryos incubated under hypoxia also showed a blunted response to acute hypoxic stress. In conclusion, the main responses elicited by chronic hypoxic incubation, namely, cardiac enlargement, blunted hypoxic response and systemic vasodilation, may provide chronically hypoxic embryos with a new physiological repertoire for responding to hypoxia.

  • 11.
    Crossley, II, Dane A.
    et al.
    University of California at Irvine.
    Hicks, James W.
    University of California at Irvine.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Ontogeny of baroreflex control in the American alligator Alligator mississippiensis2003In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 206, p. 2895-2902Article in journal (Refereed)
    Abstract [en]

     Baroreflex regulation appears in different species at different points in embryonic development. This study was designed to understand the development of the baroreflex in embryos of the American alligator at four different points of embryonic development (60%, 70%, 80% and 90% of a total incubation period of 72 days) and in 1-week-old hatchlings. Data from a separate study on 1-year-old alligators were included for comparison. The gain of the cardiac limb of the baroreflex was calculated from heart rate changes triggered by pharmacological manipulation of arterial pressure with sodium nitroprusside and phenylephrine. The results demonstrated that a vagally mediated hypertensive baroreflex was present during the final 30% of alligator development. A hypotensive baroreflex was not present in embryos but appeared in hatchlings, mediated by a combined effect of vagal and sympathetic efferents. Absolute baroreflex gain was maximal at 80% of incubation (41.22 beats kPa–1 min–1) and dropped thereafter, reaching a minimum in 1-year-old alligators (9.69 beats kPa–1 min–1). When the baroreflex gain was normalized to resting arterial pressure and heart rate, the maximum gain was observed in 1-year-old alligators (normalized index of 2.12 versus 0.75 in hatchlings and 0.69 as the highest gain in embryos). In conclusion, baroreflex regulation appeared during embryonic development with a substantial gain. These findings indicate that embryonic development is a period of preparation for cardiovascular regulatory mechanisms that will be necessary in adult life and that the baroreflex control mechanism is required for cardiovascular control during ontogeny.   

  • 12.
    Elfwing, Magnus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Fallahshahroudi, Amir
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Lindgren, Isa
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    The Strong Selective Sweep Candidate Gene ADRA2C Does Not Explain Domestication Related Changes In The Stress Response Of Chickens2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 8, p. e103218-Article in journal (Refereed)
    Abstract [en]

    Analysis of selective sweeps to pinpoint causative genomic regions involved in chicken domestication has revealed a strongselective sweep on chromosome 4 in layer chickens. The autoregulatory a-adrenergic receptor 2C (ADRA2C) gene is theclosest to the selective sweep and was proposed as an important gene in the domestication of layer chickens. The ADRA2Cpromoter region was also hypermethylated in comparison to the non-selected ancestor of all domesticated chicken breeds,the Red Junglefowl, further supporting its relevance. In mice the receptor is involved in the fight-or-flight response as itmodulates epinephrine release from the adrenals. To investigate the involvement of ADRA2C in chicken domestication, wemeasured gene expression in the adrenals and radiolabeled receptor ligand in three brain regions comparing the domesticWhite Leghorn strain with the wild ancestor Red Junglefowl. In adrenals ADRA2C was twofold greater expressed than therelated receptor gene ADRA2A, indicating that ADRA2C is the predominant modulator of epinephrine release but no straindifferences were measured. In hypothalamus and amygdala, regions associated with the stress response, and in striatum,receptor binding pIC50 values ranged between 8.1–8.4, and the level was not influenced by the genotyped allele. Becausechicken strains differ in morphology, physiology and behavior, differences attributed to a single gene may be lost in thenoise caused by the heterogeneous genetic background. Therefore an F10 advanced intercross strain between WhiteLeghorn and Red Junglefowl was used to investigate effects of ADRA2C alleles on fear related behaviors and fecundity. Wedid not find compelling genotype effects in open field, tonic immobility, aerial predator, associative learning or fecundity.Therefore we conclude that ADRA2C is probably not involved in the domestication of the stress response in chicken, and thestrong selective sweep is probably caused by selection of some unknown genetic element in the vicinity of the gene.

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  • 13.
    Elfwing, Magnus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Lindgren, Isa
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Domestication Affected Heart Rate Regulation in Juvenile Chickens2015Manuscript (preprint) (Other academic)
    Abstract [en]

    The domestication process in chickens has involved strong selection for productive traits. There is a broad understanding of phenotypic differences between domestic breeds and their ancestor, the Red Junglefowl (RJF), on fear related behaviors, genetic architecture, physiology and productive traits. Some of these characters can potentially be explained by changes in the activity of the autonomic nervous system. To address these questions we measured heart rate as a proxy for autonomic activity in the Red Junglefowl and compared it with two domestic strains, a broiler (BRO) (meat production) and a White Leghorn strain (HY) (egg production) at two and six weeks of age. Autonomic tones were pharmacologically manipulated in broilers to assess heart rate regulation during maturation. To investigate the dynamics of  autonomic control animals were measured during baseline conditions and during acute stress.

    At two weeks of age baseline heart rate was high in all strains (RJF: 541.2±18.3, HY: 506.8±38.8, BRO: 456.0±22.3) and progressively decreased with age (RJF: 491.3±10.9, HY: 386.8±25.1, BRO:_296.8±26.9). BRO had a lower heart rate compared to RJF and HY, and the differences could not be explained by allometry alone. There was a domestication effect in BRO but not HY, which were in general more similar to RJF. These findings suggest that positive selection for somatic growth has changed heart rate regulation in broilers. During acute stress heart rate did not decrease with age in the same way than baseline values, which means that there is an increased scope for raising heart rate above baseline with age. At least in broilers the increased heart rate scope is due to a recruitment in adrenergic control in absence of a patent cholinergic tone.

  • 14.
    Elfwing, Magnus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Lundegård, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Fetal development of baroreflex sensitivity: The chicken embryo as a case model2011In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 178, no 1, p. 75-83Article, review/survey (Refereed)
    Abstract [en]

    The baroreflex is the main short term compensatory mechanism to buffer blood pressure changes and maintain circulatory homeostasis. Its ontogeny and importance during prenatal life is not fully understood so we used broiler chickens to investigate the maturation of the baroreflex in late incubation using a novel method that measured changes in heart rate during spontaneous fluctuations in blood pressure. Our results suggest that a baroreflex is already functional at d17 with no indication of further maturation in terms of sensitivity (gain at 17 d was 52.9 ± 8.3 and at 20 d 69.5 ± 16.2 ms kPa−1). The physiological relevance of these values is shown using data surrogation methods. Although the results contrast with the progressive baroreflex maturation indicated by the pharmacological method, we sustain that both methods provide information on baroreflex regulation. While the spontaneous method evaluates truly physiological (but small) pressure changes, the pharmacological method provides a more consistent and repetitive challenge for the reflex that requires a different recruitment of baroreflex effectors.

  • 15.
    Elfwing, Magnus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Näsström, Åsa
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    The maturation of heart rate control in the Red Junglefowl (Gallus gallus)2015Manuscript (preprint) (Other academic)
    Abstract [en]

    Fetal development of autonomic cardiac control has been thoroughly investigated in chickens, but the maturation of the autonomic nervous system after hatching has gained little attention. At hatch the heart is under a feeble nervous control and there are indications suggesting a rapid maturation process during the first two weeks of postnatal life. We aimed to characterize the maturation by measuring heart rate at baseline and stressful conditions during the first 5 weeks of life in the Red Junglefowl and using autonomic antagonists to quantify the contribution of sympathetic and parasympathetic activity. We also compared the Red Junglefowl to the domestic broiler chickens at hatch to investigate the impact of domestication processes on heart rate regulation.

    During the first two postnatal weeks, baseline and stress heart rate progressively increased. After two weeks baseline heart rate decreased while heart rate during acute stress remained high. Adrenergic tone in Red Junglefowl increased as well early suggesting that the increase in heart rate was driven predominantly by adrenergic contributions. The adrenergic tone decreased by age after postnatal week one explaining the concomitant reduction in basal heart rate during this period. Broiler chickens possessed a strong cholinergic tone at hatch indicating that parasympathetic control has been favored perhaps due to heavy selection for somatic growth.

  • 16.
    Eme, John
    et al.
    Department of Biological Sciences, University of North Texas, Denton, USA.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Hicks, James W
    Deepartment of Ecology and Evolutionary Biology, University of California Irvine, Irvine, USA.
    Crossley II, Dane A.
    Department of Biological Sciences, University of North Texas, Denton, USA.
    Hypoxic alligator embryos: Chronic hypoxia, catecholamine levels and autonomic responses of in ovo alligators2011In: Comparative Biochemistry and Physiology - Part A: Comparative Physiology, ISSN 0300-9629, Vol. 160, no 3, p. 412-420Article in journal (Refereed)
    Abstract [en]

    Hypoxia is a naturally occurring environmental challenge for embryonic reptiles, and this is the first study to investigate the impact of chronic hypoxia on the in ovo development of autonomic cardiovascular regulation and circulating catecholamine levels in a reptile. We measured heart rate (fH) and chorioallantoic arterial blood pressure (MAP) in normoxic (‘N21’) and hypoxic-incubated (‘H10’; 10% O2) American alligator embryos (Alligator mississippiensis) at 70, 80 and 90% of development. Embryonic alligator responses to adrenergic blockade with propranolol and phentolamine were very similar to previously reported responses of embryonic chicken, and demonstrated that embryonic alligator has α and β-adrenergic tone over the final third of development. However, adrenergic tone originates entirely from circulating catecholamines and is not altered by chronic hypoxic incubation, as neither cholinergic blockade with atropine nor ganglionic blockade with hexamethonium altered baseline cardiovascular variables in N21 or H10 embryos. In addition, both atropine and hexamethonium injection did not alter the generally depressive effects of acute hypoxia — bradycardia and hypotension. However, H10 embryos showed significantly higher levels of noradrenaline and adrenaline at 70% of development, as well as higher noradrenaline at 80% of development, suggesting that circulating catecholamines reach maximal levels earlier in incubation for H10 embryos, compared to N21 embryos. Chronically elevated levels of catecholamines may alter the normal balance between α and β-adrenoreceptors in H10 alligator embryos, causing chronic bradycardia and hypotension of H10 embryos measured in normoxia.

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  • 17.
    Fallahsharoudi, Amir
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Løtvedt, Pia
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Beltéky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Changes in pituitary gene expression may underlie multiple domesticated traits in chickens.2019In: Heredity, ISSN 0018-067X, E-ISSN 1365-2540, Vol. 122, no 2, p. 195-204Article in journal (Refereed)
    Abstract [en]

    Domesticated animals share a unique set of morphological and behavioral traits, jointly referred to as the domesticated phenotype. Striking similarities amongst a range of unrelated domesticated species suggest that similar regulatory mechanisms may underlie the domesticated phenotype. These include color pattern, growth, reproduction, development and stress response. Although previous studies have focused on the brain to find mechanisms underlying domestication, the potential role of the pituitary gland as a target of domestication is highly overlooked. Here, we study gene expression in the pituitary gland of the domesticated White Leghorn chicken and its wild ancestor, the Red Junglefowl. By overlapping differentially expressed genes with a previously published list of functionally important genes in the pituitary gland, we narrowed down to 34 genes. Amongst them, expression levels of genes with inhibitory function on pigmentation (ASIP), main stimulators of metabolism and sexual maturity (TSHB and DIO2), and a potential inhibitor of broodiness (PRLR), were higher in the domesticated breed. Additionally, expression of 2 key inhibitors of the stress response (NR3C1, CRHR2) was higher in the domesticated breed. We suggest that changes in the transcription of important modulatory genes in the pituitary gland can account not only for domestication of the stress response in domestic chickens, but also for changes in pigmentation, development, and reproduction. Given the pivotal role of the pituitary gland in the regulation of multiple shared domesticated traits, we suggest that similar changes in pituitary transcriptome may contribute to the domesticated phenotype in other species as well.

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  • 18.
    Farrell, A. P.
    et al.
    University of British Columbia, Vancouver, Canada.
    Altimitas, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Franklin, C. E.
    University of Queensland, Brisbane, Australia.
    Axelsson, M.
    University of Gothenburg, Sweden.
    Niche expansion of the shorthorn sculpin (Myoxocephalus scorpius) to Arctic waters is supported by a thermal independence of cardiac performance at low temperature2013In: Canadian Journal of Zoology, ISSN 0008-4301, E-ISSN 1480-3283, Vol. 91, no 8, p. 573-580Article in journal (Refereed)
    Abstract [en]

    Cardiovascular adaptations that permit successful exploitation of polar marine waters by fish requires a capacity tonegate or compensate for the depressive effects of low temperatures on physiological processes. Here, we examined the effectsof acute and chronic temperature change on the maximum cardiac performance of shorthorn sculpin (Myoxocephalusscorpius (L., 1758)) captured above the Arctic Circle. Our aim was to establish if the sculpin’s success at low temperatures wasachieved through thermal independence of cardiac function or via thermal compensation as a result of acclimation. Maximumcardiac performance was assessed at both 1 and 6 °C with a working perfused heart preparation that was obtained after fish hadbeen acclimated to either 1 or 6 °C. Thus, tests were performed at the fish’s acclimation temperature and with an acutetemperature change. Maximum cardiac output, which was relatively large (>50 mL·min−1·kg−1 body mass) for a benthic fish at afrigid temperature, was found to be independent of both acclimation temperature and test temperature. While maximum-adrenergic stimulation produced positive chronotropy at both acclimation temperatures, inotropic effects were weak orabsent. We conclude that thermal independence of cardiac performance at low temperature likely facilitated the exploitation ofpolar waters by the shorthorn sculpin.

  • 19.
    Farrell, Anthony P.
    et al.
    Faculty of Agricultural Sciences and Department of Zoology University of British Columbia, Vancouver, Canada.
    Axelsson, Michael
    Department of Zoology Göteborg University.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Sandblom, Erik
    Department of Zoology Göteborg University.
    Claireaux, Guy
    Département de Biologie Intégrative 1 Quai de la Daurade, 34200 Sète, France.
    Maximum cardiac performance and adrenergic sensitivity of the sea bass Dicentrarchus labrax at high temperatures2007In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 210, p. 1216-1224Article in journal (Refereed)
    Abstract [en]

    We examined maximum cardiac performance of sea bass Dicentrarchus labrax acclimated to 18°C and 22°C, temperatures near the optimum for growth of this species. Our aim was to study whether cardiac performance, especially the effect of adrenergic stimulation, differed when compared to salmonids. Sea bass and salmonids are both athletic swimmers but their cardiac anatomy differs markedly. The sea bass ventricle does not receive any oxygenated blood via a coronary circulation while salmonids have a well-developed arterial supply of oxygen to the compact layer of the ventricle. Using in situ perfused heart preparations, maximum cardiac performance of 18°C-acclimated sea bass (i.e. cardiac output=90.8± 6.6 ml min–1 kg–1 and power output=11.41±0.83 mW g–1) was found to be comparable to that previously reported for rainbow trout Oncorhynchus mykiss and brown trout Salmo trutta at similar temperatures and with tonic adrenergic (5 nmol l–1 adrenaline) stimulation. For 22°C-acclimated sea bass, heart rate was significantly higher, but maximum stroke volume was reduced by 22% (1.05±0.05 ml kg–1) compared with 18°C (1.38± 0.11 ml kg–1). As a result, maximum cardiac output (99.4±3.9 ml min–1 kg–1) was not significantly different at 22°C. Instead, maximum power output was 27% higher at 22°C (14.95±0.96 mW g–1) compared with 18°C, primarily because of the smaller relative ventricular mass in 22°C-acclimated sea bass. Compared with tonic adrenergic stimulation with 5 nmol l–1 adrenaline, maximum adrenergic stimulation of the sea bass heart produced only modest stimulatory effects at both temperatures (12–13% and 14–15% increases in maximum cardiac output and power output, respectively, with no chronotropic effect). Adrenergic stimulation also increased the cardiac sensitivity to filling pressure, with the maximum left-shift in the Starling curve being produced by 50–100 nmol l–1 adrenaline at 18°C and 10–50 nmol l–1 adrenaline at 22°C. We show that the sea bass, which lacks a coronary arterial oxygen supply to the ventricle, has a powerful heart. Its maximum performance is comparable to a salmonid heart, as is the modest stimulatory effect of adrenaline at high temperature.

  • 20.
    Franklin, Craig E.
    et al.
    University of Queensland, Brisbane, Australia.
    Farrell, Anthony P.
    University of British Columbia, Vancouver, Canada.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Axelsson, Michael
    University of Gothenburg, Sweden.
    Thermal dependence of cardiac function in arctic fish: implications of a warming world2013In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 216, p. 4251-4255Article in journal (Refereed)
    Abstract [en]

    With the Arctic experiencing one of the greatest and most rapid increases in sea temperatures in modern time, predicting how Arctic marine organisms will respond to elevated temperatures has become crucial for conservation biology. Here, we examined the thermal sensitivity of cardiorespiratory performance for three closely related species of sculpins that inhabit the Arctic waters, two of which, Gymnocanthus tricuspis and Myoxocephalus scorpioides, have adapted to a restricted range within the Arctic, whereas the third species, Myoxocephalus scorpius, has a wider distribution. We tested the hypothesis that the fish restricted to Arctic cold waters would show reduced cardiorespiratory scope in response to an increase in temperature, as compared with the more eurythermal M. scorpius. As expected from their biogeography, M. scorpioides and G. tricuspis maximised cardiorespiratory performance at temperatures between 1 and 4 degrees C, whereas M. scorpius maximised performance over a wider range of temperatures (1-10 degrees C). Furthermore, factorial scope for cardiac output collapsed at elevated temperature for the two high-latitude species, negatively impacting their ability to support aerobically driven metabolic processes. Consequently, these results concurred with our hypothesis, suggesting that the sculpin species restricted to the Arctic are likely to be negatively impacted by increases in ocean temperatures.

  • 21.
    Hansen, J.
    et al.
    Department of Zoophysiology, University of Aarhus, DK-8000 Århus C, Denmark.
    Gesser, H.
    Department of Zoophysiology, University of Aarhus, DK-8000 Århus C, Denmark.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Mechanical efficiency of the trout heart during volume and pressure-loading: Metabolic implications of the stiffness of the ventricular tissue2002In: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology, ISSN 0174-1578, E-ISSN 1432-136X, Vol. 172, no 6, p. 477-484Article in journal (Refereed)
    Abstract [en]

    In the mammalian heart the metabolic costs of pressure loading exceed those of volume loading. As evidence suggests that the opposite may be true in fish, we evaluated the metabolic costs of volume and pressure loading in the isolated trout heart and compared the results with the mammalian heart based on the biomechanical properties of cardiac muscle. The highest power output (2.33 ± 0.32 mW g-1, n = 5) appeared at the highest preload pressure tested (0.3 kPa) and at an afterload of 5 kPa. At a higher afterload, power did not increase because stroke volume fell. The highest mechanical efficiency (20.7 ± 2.0%, n = 5) was obtained at a preload of 0.15 kPa and an afterload of 5 kPa. Further increases in preload or afterload did not increase mechanical efficiency, probably because of increases in ventricular wall stress which increased the oxygen consumed disproportionately more than the stroke work. Under pressure unloading (25% decrease in power output), mechanical efficiency was significantly higher in comparison with volume unloading. Given that stiffness of the ventricular tissue is larger in trout than in rat papillary muscles, it is suggested that the increased strain during volume loading is energetically disadvantageous for stiff muscles like those of trout, but it is advantageous when muscle stiffness is lower as it occurs in the rat papillary muscle.

  • 22.
    Joyce, William
    et al.
    Department of Zoophysiology, Aarhus University, Aarhus, Denmark.
    Axelsson, Michael
    Department of Biological and Environmental Sciences, University of Gothenburg, Gothenburg, Sweden..
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wang, Tobias
    Department of Zoophysiology, Aarhus University, Aarhus, Denmark..
    In situ cardiac perfusion reveals interspecific variation of intraventricular flow separation in reptiles2016In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 219, no pt 14, p. 2220-2227Article in journal (Refereed)
    Abstract [en]

    The ventricles of non-crocodilian reptiles are incompletely dividedand provide an opportunity for mixing of oxygen-poor blood andoxygen-rich blood (intracardiac shunting). However, both cardiacmorphology and in vivo shunting patterns exhibit considerableinterspecific variation within reptiles. In the present study, wedevelop an in situ double-perfused heart approach to characterisethe propensity and capacity for shunting in five reptile species: theturtle Trachemys scripta, the rock python Python sebae, the yellowanaconda Eunectes notaeus, the varanid lizard Varanusexanthematicus and the bearded dragon Pogona vitticeps. Tosimulate changes in vascular bed resistance, pulmonary andsystemic afterloads were independently manipulated and changesin blood flow distribution amongst the central outflow tracts weremonitored. As previously demonstrated in Burmese pythons, rockpythons and varanid lizards exhibited pronounced intraventricularflow separation. As pulmonary or systemic afterload was raised, flowin the respective circulation decreased. However, flow in the othercirculation, where afterload was constant, remained stable. Thiscorrelates with the convergent evolution of intraventricular pressureseparation and the large intraventricular muscular ridge, whichcompartmentalises the ventricle, in these species. Conversely, inthe three other species, the pulmonary and systemic flows werestrongly mutually dependent, such that the decrease in pulmonaryflow in response to elevated pulmonary afterload resulted inredistribution of perfusate to the systemic circuit (and vice versa).Thus, in these species, the muscular ridge appeared labile and bloodcould readily transverse the intraventricular cava. We conclude thatrelatively minor structural differences between non-crocodilianreptiles result in the fundamental changes in cardiac function.Further, our study emphasises that functionally similar intracardiacflow separation evolved independently in lizards (varanids) andsnakes (pythons) from an ancestor endowed with the capacity forlarge intracardiac shunts.

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  • 23.
    Lindgren, Isa
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Chronic prenatal hypoxia sensitizes beta-adrenoceptors in the embryonic heart but causes postnatal desensitization2009In: AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, ISSN 0363-6119, Vol. 297, no 2, p. R258-R264Article in journal (Refereed)
    Abstract [en]

    Prenatal hypoxia in mammals causes fetal growth restriction and catecholaminergic overstimulation that, in turn, alter signaling pathways associated with adrenergic receptors. beta-Adrenoceptors (beta-ARs) are essential for fetal cardiac development and regulation of cardiac contractility. We studied the effects of chronic prenatal hypoxia on cardiac beta-AR signaling and the incidence of alterations in the juvenile beta-AR system due to the embryonic treatment. We measured functional beta-AR density (B-max) through binding with [H-3]CGP-12177 and the effect of agonists on beta-AR-dependent contractility (pEC(50)) through concentration-response curves to epinephrine. Eggs from broiler chickens were incubated in normoxia (N, 21% O-2) or chronic hypoxia (H, 14% O-2). Cardiac tissue from embryos and juveniles was used (15 and 19 day of embryonic development and 14 and 35 days posthatching, E19, E15, P14, and P35, respectively). Relative cardiac enlargement was found in the hypoxic groups at E15, E19, and P14, but not P35. B-max significantly decreased in E19H. Bmax more than doubled posthatching but decreased from P14 to P35. The sensitivity to epinephrine was lower in E19N compared with E15N, but hypoxia increased the sensitivity to agonist in both E15H and E19H. Despite maintained receptor density, the P35H juvenile displayed a decreased sensitivity to beta-AR agonist, something that was not seen in P14H. The postnatal decrease in beta-AR sensitivity as an effect of chronic prenatal hypoxia, without a concomitant change in beta-AR density, leads us to conclude that the embryonic hypoxic challenge alters the future progression of beta-AR signaling and may have important implications for cardiovascular function in the adult.

  • 24.
    Lindgren, Isa
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Sensitivity of organ growth to chronically low oxygen levels during incubation in Red Junglefowl and domesticated chicken breeds2011In: Poultry Science, ISSN 0032-5791, E-ISSN 1525-3171, Vol. 90, no 1, p. 126-135Article in journal (Refereed)
    Abstract [en]

    Genetic selection programs have imposed large phenotypic changes in domesticated chicken breeds that are also apparent during embryonic development. Broilers, for example, have a faster growth rate before hatching in comparison with White Leghorns, indicating that the allocation of resources toward different functions already begins before hatching. Therefore, we hypothesized that embryonic organ growth would follow different developmental trajectories and would be differentially affected by an oxygen shortage during incubation. Heart, brain, and liver growth were studied in broiler, White Leghorn, and Red Junglefowl embryos at embryonic (E) ages E11, E13, E15, E18, and E20, and the results were fitted to growth allometric equations to determine the degree of organ stunting or sparing caused by low oxygen during incubation. Hypoxia caused a 3-fold larger mortality in Red Junglefowl than in the domesticated breeds, with a similar impairment of embryonic growth of 18%, coupled with a reduction in yolk utilization of 56%. Relative brain size was not affected by hypoxia in any breed, but a substantial stunting effect was observed for the liver and heart at late embryonic ages, with marked differences between breeds. In Red Junglefowl, only the heart was stunted. In White Leghorns, only the liver was stunted, and in broilers, both organs were stunted. These results can be explained in terms of the selection pressure on long-term production traits (reproductive effort) in White Leghorns, requiring a more efficient lipid metabolism, compared with the selection pressure on shorter-term production traits (growth) in broilers, requiring overall metabolic turnover and convective nutrient delivery to all tissues. At the same time, a remarkable sparing of the heart was observed in broilers and Red Junglefowl between E11 and E15, which suggests that cardiac growth can be manipulated during embryonic development. This result could be relevant for manipulating the phenotype of the heart for management purposes at a developmental stage when the bird is most versatile and phenotypically malleable.

  • 25.
    Lindgren, Isa
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Altimitas, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Prenatal hypoxia programs changes in β-adrenergic signaling and postnatal cardiac contractile dysfunction2013In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 305, p. R1093-R1101Article in journal (Refereed)
    Abstract [en]

    Prenatal hypoxia leads to an increased risk of adult cardiovascular disease. We have previously demonstrated a programming effect of prenatal hypoxia on the cardiac β-adrenergic (βAR) response. The aim of this study was to determine 1) whether the decrease in βAR sensitivity in prenatally hypoxic 5-wk old chicken hearts is linked to changes in β1AR/β2ARs, Gαi expression and cAMP accumulation and 2) whether prenatal hypoxia has an effect on heart function in vivo. We incubated eggs in normoxia (N, 21% O2) or hypoxia from day 0 (H, 14% O2) and raised the posthatchlings to 5 wk of age. Cardiac β1AR/β2ARs were assessed through competitive binding of [3H]CGP-12177 with specific β1AR or β2AR blockers. Gαs and Gαi proteins were assessed by Western blot and cAMP accumulation by ELISA. Echocardiograms were recorded in anesthetized birds to evaluate diastolic/systolic diameter and heart rate and tissue sections were stained for collagen. We found an increase in relative heart mass, β1ARs, and Gαs in prenatally hypoxic hearts. cAMP levels after isoproterenol stimulation and collagen content was not changed in H compared with N, but in vivo echocardiograms showed systolic contractile dysfunction. The changes in βAR and G protein subtypes may be indicative of an early compensatory stage in the progression of cardiac dysfunction, further supported by the cardiac hypertrophy and systolic contractile dysfunction. We suggest that it is not the changes in the proximal part of the βAR system that causes the decreased cardiac contractility, but Ca2+ handling mechanisms further downstream in the βAR signaling cascade.

  • 26.
    Lindgren, Isa
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Crossley II, Dane
    Biology Department, University of North Dakota, USA.
    Villamor, Eduardo
    Department of Pediatrics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC+), The Netherlands.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Hypotension in the chronically hypoxic chicken embryo is related to the β-adrenergic response of chorioallantoic and femoral arteries and not to bradycardia2011In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 301, no 4, p. R1161-R1168Article in journal (Refereed)
    Abstract [en]

    Prolonged fetal hypoxia leads to growth restriction and can cause detrimental pre- and postnatal alterations. The embryonic chicken is a valuable model to study such effects of prenatal hypoxia, but little is known about long-term hypoxic effects on cardiovascular regulation in the chicken embryo. We investigated heart rate and blood pressure responses to chronic prenatal hypoxia in the chicken embryo (19 days) and hypothesized that it would exhibit hypotension due to bradycardia and βAR-mediated relaxation of the systemic (femoral) and/or the chorioallantoic (CA) arteries. We first measured heart rate (HR) and blood pressure (BP) in 19 day embryos incubated from day 0 in normoxia or hypoxia (14-15% O2). Secondly, we studied β-adrenoceptor (βAR)-mediated contraction, relaxation to the β-adrenoceptor (βAR) agonist isoproterenol and relaxation to forskolin in femoral and CA arteries using wire myography techniques. Chronic hypoxia caused a close to significant hypotension compared to the controls (Mean arterial pressure 3.19±0.18 vs. 2.59±0.13 kPa, normoxia vs. hypoxia respectively, P=0.056), but not bradycardia. All vessels relaxed in response to βAR stimulation with isoproterenol, but the CAM arteries completely lacked an βAR response. Furthermore, hypoxia increased the sensitivity of femoral (but not CA arteries) to isoproterenol. Hypoxia also increased the responsiveness of femoral arteries to the adenylate cyclase activator forskolin. In conclusion, hypotension in chronically hypoxic chicken embryos is more likely the consequence of elevated levels of circulating catecholamines acting on vascular beds with exclusive (CA arteries) or exacerbated (femoral arteries) βAR-mediated relaxation, rather than a consequence of bradycardia.

  • 27.
    Lindholm, Caroline
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Physiological and behavioral effects of intermittent fasting vs daily caloric restriction in meat-type poultry2023In: Animal, ISSN 1751-7311, E-ISSN 1751-732X, Vol. 17, no 6, article id 100849Article in journal (Refereed)
    Abstract [en]

    Intermittent fasting (IF) is the practice of temporal food restriction to promote metabolic switching between a glucose- and a ketone-based metabolism, which has been reported to come with diverse health benefits. IF practices appear to confer many of the advantages of caloric restriction without restricting total energy intake, and studies in both rodents and humans suggest organism-wide improvements in neurological, cardiovascular and metabolic health. IF is also commonly employed in the commercial rearing of breeding meat-type poultry, i.e. broiler breeders, which require strict feed restriction throughout life to maintain physical health. While the scientific poultry literature holds vast amounts of data on such “skip-a-day” feeding schedules, it has been unclear to what extent avian and mammalian literature may be compared as broiler breeders are typically feed-restricted to around 30% of ad libitum intake even in IF schedules. In this study we set out to disentangle the effects of IF and caloric restriction in meat-type poultry by employing both IF and daily feeding schedules at two different restriction levels. Our results suggest that the physiological response to IF in chickens is only marginally affected by the intensity of feed restriction, while behavioural parameters are more closely related to feeding level and are expected to better mirror animal welfare. Our results suggest that avian and mammalian literature on IF should be comparable. Meat-type chickens do show some peculiarities in response to IF, such as a reduced insulin sensitivity, but it is currently unclear whether this is true for all chickens or is an effect of the intense selection for rapid growth in meat-type chickens.

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  • 28.
    Lindholm, Caroline
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Point-of-care devices for physiological measurements in field conditions. A smorgasbord of instruments and validation procedures2016In: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 202, p. 99-111Article, review/survey (Refereed)
    Abstract [en]

    Point-of-care (POC) devices provide quick diagnostic results that increase the efficiency of patient care. Many POC devices are currently available to measure metabolites, blood gases, hormones, disease biomarkers or pathogens in samples as diverse as blood, urine, feces or exhaled breath. This diversity is potentially very useful for the comparative physiologist in field studies if proper validation studies are carried out to justify the accuracy of the devices in non-human species under different conditions. Our review presents an account of physiological parameters that can be monitored with POC devices and surveys the literature for suitable quantitative and statistical procedures for comparing POC measurements with reference “gold standard” procedures. We provide a set of quantitative tools and report on different correlation coefficients (Lin's Concordance Correlation Coefficient or the more widespread Pearson correlation coefficient), describe the graphical assessment of variation using Bland–Altman plots and discuss the difference between Model I and Model II regression procedures. We also report on three validation datasets for lactate, glucose and hemoglobin measurements in birds using the newly proposed procedures. We conclude the review with a haphazard account of future developments in the field, emphasizing the interest in lab-on-a-chip devices to carry out more complex experimental measurements than the ones currently available in POC devices.

  • 29.
    Lindholm, Caroline
    et al.
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biology.
    Batakis, Petros
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Lees, John
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Intermittent fasting induces chronic changes in the hepatic gene expression of Red Jungle Fowl (Gallus gallus)2022In: BMC Genomics, E-ISSN 1471-2164, Vol. 23, no 1, article id 304Article in journal (Refereed)
    Abstract [en]

    Background

    Intermittent fasting (IF), the implementation of fasting periods of at least 12 consecutive hours on a daily to weekly basis, has received a lot of attention in recent years for imparting the life-prolonging and health-promoting effects of caloric restriction with no or only moderate actual restriction of caloric intake. IF is also widely practiced in the rearing of broiler breeders, the parent stock of meat-type chickens, who require strict feed restriction regimens to prevent the serious health problems associated with their intense appetites. Although intermittent fasting has been extensively used in this context to reduce feed competition and its resulting stress, the potential of IF in chickens as an alternative and complementary model to rodents has received less investigation. In both mammals and birds, the liver is a key component of the metabolic response to IF, responding to variations in energy balance. Here we use a microarray analysis to examine the liver transcriptomics of wild-type Red Jungle Fowl chickens fed either ad libitum, chronically restricted to around 70% of ad libitum daily or intermittently fasted (IF) on a 2:1 (2 days fed, 1 day fasted) schedule without actual caloric restriction. As red junglefowl are ancestral to domestic chicken breeds, these data serve as a baseline to which existing and future transcriptomic results from farmed birds such as broiler breeders can be compared.

    Results

    We find large effects of feeding regimen on liver transcriptomics, with most of the affected genes relating to energy metabolism. A cluster analysis shows that IF is associated with large and reciprocal changes in genes related to lipid and carbohydrate metabolism, but also chronic changes in genes related to amino acid metabolism (generally down-regulated) and cell cycle progression (generally up-regulated). The overall transcription pattern appears to be one of promoting high proliferative plasticity in response to fluctuations in available energy substrates. A small number of inflammation-related genes also show chronically changed expression profiles, as does one circadian rhythm gene.

    Conclusions

    The increase in proliferative potential suggested by the gene expression changes reported here indicates that birds and mammals respond similarly to intermittent fasting practices. Our findings therefore suggest that the health benefits of periodic caloric restriction are ubiquitous and not restricted to mammals alone. Whether a common fundamental mechanism, for example involving leptin, underpins these benefits remains to be elucidated.

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  • 30.
    Lindholm, Caroline
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Calais, A
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jönsson, J
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Yngwe, N.
    SweHatch AB, 247 47 Flyinge, Sweden.
    Berndtson, E.
    SweHatch AB, 247 47 Flyinge, Sweden.
    Hult, E.
    SweHatch AB, 247 47 Flyinge, Sweden.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, Faculty of Science & Engineering.
    Slow and steady wins the race? No signs of reduced welfare in smallerbroiler breeder hens at four weeks of age2015In: Animal Welfare, ISSN 0962-7286, Vol. 24, no 4, p. 447-454Article in journal (Refereed)
    Abstract [en]

    Broiler breeder chickens are commonly reared under strict feed-restriction regimes to reduce obesity-induced health and fertilityproblems during adult life, and are assumed to experience a reduced welfare due to the resulting hunger. In these conditions, feedcompetition could influence the growth rate, so that the individuals falling behind in growth would experience more stress and hunger.We hypothesised that these chickens are poor competitors due to a reactive coping style and experience a further reduced welfaresituation before size-sorting (‘grading’) at four weeks of age. Our results from open field, tonic immobility and home pen activity monitoringshow signs of lower fear and higher home-pen activity levels in smaller hens and do not support the idea of reactive coping.H/L ratios of smaller hens were also found to be lower, indicating less stress in these birds. Dissections of smaller and larger fourweekbreeder hens may offer an explanation in the form of a relatively larger gastrointestinal tract in smaller birds. We argue thatthis is a form of habituation to restricted feeding, offering these birds a physiological stress coping mechanism, and that low earlygrowth rate may not always be a sign of poorer welfare in broiler breeders.

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  • 31.
    Løtvedt, Pia
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Fallahshahroudi, Amir
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bektic, Lejla
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Chicken domestication changes expression of stress-related genes in brain, pituitary and adrenals2017In: Neurobiology of stress, ISSN 2352-2895, Vol. 7, p. 113-121Article in journal (Refereed)
    Abstract [en]

    Domesticated species have an attenuated behavioral and physiological stress response compared to their wild counterparts, but the genetic mechanisms underlying this change are not fully understood. We investigated gene expression of a panel of stress response-related genes in five tissues known for their involvement in the stress response: hippocampus, hypothalamus, pituitary, adrenal glands and liver of domesticated White Leghorn chickens and compared it with the wild ancestor of all domesticated breeds, the Red Junglefowl. Gene expression was measured both at baseline and after 45 min of restraint stress. Most of the changes in gene expression related to stress were similar to mammals, with an upregulation of genes such as FKBP5, C-FOS and EGR1 in hippocampus and hypothalamus and StAR, MC2R and TH in adrenal glands. We also found a decrease in the expression of CRHR1 in the pituitary of chickens after stress, which could be involved in negative feedback regulation of the stress response. Furthermore, we observed a downregulation of EGR1 and C-FOS in the pituitary following stress, which could be a potential link between stress and its effects on reproduction and growth in chickens. We also found changes in the expression of important genes between breeds such as GR in the hypothalamus, POMC and PC1 in the pituitary and CYP11A1 and HSD3B2 in the adrenal glands. These results suggest that the domesticated White Leghorn may have a higher capacity for negative feedback of the HPA axis, a lower capacity for synthesis of ACTH in the pituitary and a reduced synthesis rate of corticosterone in the adrenal glands compared to Red Junglefowl. All of these findings could explain the attenuated stress response in the domesticated birds.

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    Chicken domestication changes expression of stress-related genes in brain, pituitary and adrenals.
  • 32.
    Milberg, Per
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Ecology . Linköping University, The Institute of Technology.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Amundin, M
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Bergman, Karl-Olof
    Linköping University, Department of Physics, Chemistry and Biology, Ecology . Linköping University, The Institute of Technology.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Wahlström, Dan
    Linköping University, Department of Physics, Chemistry and Biology, Ecology . Linköping University, The Institute of Technology.
    Precision i poängsättning av essäfrågor och examensarbeten: implikationer för betyg enligt ECTS2006In: Nya vilkor för lärande och undervisning. 9:e universitetspedagogiska konferensen vid Linköpings universitet 17 oktober 2005,2005, Linköping: Linköpings universitet , 2006, p. 167-Conference paper (Refereed)
  • 33.
    Nyman, Elin
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. CVMD iMED DMPK AstraZeneca R&D, Mölndal, Sweden.
    Lindgren, Isa
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Lövfors, William
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Lundengård, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Cervin, Ida
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Arbring, Theresia
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering.
    Altimitas, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Cedersund, Gunnar
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mathematical modeling improves EC50 estimations from classical dose–response curves2015In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 282, no 5, p. 951-962Article in journal (Refereed)
    Abstract [en]

    The beta-adrenergic response is impaired in failing hearts. When studying beta-adrenergic function in vitro, the half-maximal effective concentration (EC50) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50. Instead, we have applied a mathematical modeling approach to interpret the full dose–response curvein a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose–response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180–525 nM) is higher than the classically interpreted EC50 (46–191 nM). Mathematical modeling thus makes it possible to reinterpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible.

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  • 34.
    Sandbom, Erik
    et al.
    Department of Zoology, Göteborg University.
    Farrell, Anthony P
    University of British Columbia, Canada.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Axelsson, Michael
    Department of Zoology, Göteborg University.
    Claireau, Guy
    Place du Séminaire, L'Houmeau, France .
    Cardiac preload and venous return in swimming sea bass (Dicentrarchus labrax L.)2005In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 208, p. 1927-1935Article in journal (Refereed)
    Abstract [en]

    Cardiac preload (central venous pressure, P(CV), mean circulatory filling pressure (MCFP), dorsal aortic blood pressure (P(DA)) and relative cardiac output (Q) were measured in sea bass (Dicentrarchus labrax) at rest and while swimming at 1 and 2 BL s(-1). MCFP, an index of venous capacitance and the upstream venous pressure driving the return of venous blood to the heart, was measured as the plateau in Pcv during ventral aortic occlusion. Compared with resting values, swimming at 1 and 2 BL s(-1) increased Q (by 15+/-1.5 and 38+/-6.5%, respectively), P(CV) (from 0.11+/-0.01 kPa to 0.12+/-0.01 and 0.16+/-0.02 kPa, respectively), MCFP (from 0.27+/-0.02 kPa to 0.31+/-0.02 and 0.40+/-0.04 kPa, respectively) and the calculated pressure gradient for venous return (DeltaP(V), from 0.16+/-0.01 kPa to 0.18+/-0.02 and 0.24+/-0.02 kPa, respectively), but not P(DA). In spite of an increased preload, the increase in Q was exclusively mediated by an increased heart rate (f(H), from 80+/-4 beats min(-1) to 88+/-4 and 103+/-3 beats min(-1), respectively), and stroke volume (Vs) remained unchanged. Prazosin treatment (1 mg kg(-1) Mb) abolished pressure and flow changes during swimming at 1 BL s(-1), but not 2 BL s(-1), indicating that other control systems besides an alpha-adrenoceptor control are involved. This study is the first to address the control of venous capacitance in swimming fish. It questions the generality that increased Q during swimming is regulated primarily through Vs and shows that an increased cardiac filling pressure does not necessarily lead to an increased Vs in fish, but may instead compensate for a reduced cardiac filling time.

  • 35.
    Svensson Holm, Ann-Charlotte B
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Lindgren, Isa
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Österman, Hanna
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Thyroid hormone does not induce maturation of embryonicchicken cardiomyocytes in vitro2014In: Physiological Reports, E-ISSN 2051-817X, Vol. 2, no 12, p. e12182-Article in journal (Refereed)
    Abstract [sv]

    Fetal cardiac growth in mammalian models occurs primarily by cell proliferation(hyperplasia). However, most cardiomyocytes lose the ability to proliferateclose to term and heart growth continues by increasing cell size(hypertrophy). In mammals, the thyroid hormone triiodothyronine (T3) is animportant driver of this process. Chicken cardiomyocytes, however, keep theirproliferating ability long after hatching but little information is available onthe mechanisms controlling cell growth and myocyte maturation in thechicken heart. Our aim was to study the role of T3 on proliferation and differentiationof embryonic chicken cardiomyocytes (ECCM), enzymaticallyisolated from 19-day-old embryos and to compare the effects to those of insulin-like growth factor-1 (IGF-1) and phenylephrine (PE). Hyperplasia wasmeasured using a proliferation assay (MTS) and hypertrophy/multinucleationwas analyzed morphologically by phalloidin staining of F-actin and nuclearstaining with DAPI. We show that IGF-1 induces a significant increase inECCM proliferation (30%) which is absent with T3 and PE. PE induced bothhypertrophy (61%) and multinucleation (41%) but IGF-1 or T3 did not. Inconclusion, we show that T3 does not induce maturation or proliferation ofcardiomyocytes, while IGF-1 induces cardiomyocyte proliferation and PEinduces maturation of cardiomyocytes.

  • 36.
    Wang, Tobias
    et al.
    Department of Zoophysiology University of Aarhus, Denmark.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Klein, Wilfried
    Institute of Zoology University of Bonn, Germany.
    Axelsson, Michael
    Department of Zoology University of Gothenburg.
    Ventricular haemodynamics in Python molurus: Separation of pulmonary and systemic pressures2003In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 206, no 23, p. 4241-4245Article in journal (Refereed)
    Abstract [en]

    Vascular pressure separation by virtue of a two-chambered ventricle evolved independently in mammals and birds from a reptilian ancestor with a single ventricle, and allowed for high systemic perfusion pressure while protecting the lungs from oedema. Within non-crocodilian reptiles, ventricular pressure separation has only been observed in varanid lizards and has been regarded as a unique adaptation to an active predatory life style and high metabolic rate. The systemic and pulmonary sides of the ventricle in Python molurus are well separated by the muscular ridge, and a previous study using in situ perfusion of the heart revealed a remarkable flow separation and showed that the systemic side can sustain higher output pressures than the pulmonary side. Here we extend these observations by showing that systemic blood pressure Psys exceeded pulmonary pressure Ppul almost seven times (75.7±4.2 versus 11.6±1.1 cm H2O). The large pressure difference between the systemic and pulmonary circulation persisted when Psys was altered by infusion of sodium nitroprusside or phenylephrine. Intraventricular pressures, measured in anaesthetised snakes, showed an overlap in the pressure profile between the pulmonary side of the ventricle (cavum pulmonale) and the pulmonary artery, while the higher pressure in the systemic side of the ventricle (cavum arteriosum) overlapped with the pressure in the right aortic arch. This verifies that the pressure differences originate within the ventricle, indicating that the large muscular ridge separates the ventricle during cardiac contraction.

  • 37.
    Zupan, Manja
    et al.
    Swedish University of Agricultural Sciences, Department of Animal Environment and Health, Box 7068, Uppsala, SE-750 07, Uppsala, Sweden.
    Buskas, Julia
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Keeling, Linda J.
    Swedish University of Agricultural Sciences, Department of Animal Environment and Health, Box 7068, Uppsala, SE-750 07, Uppsala, Sweden.
    Assessing positive emotional states in dogs using heart rate and heartrate variability2016In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 155, p. 102-111Article in journal (Refereed)
    Abstract [en]

    Since most animal species have been recognized as sentient beings, emotional state may be a good indicator ofwelfare in animals. The goal of this study was to manipulate the environment of nine beagle research dogs tohighlight physiological responses indicative of different emotional experiences. Stimuli were selected to be amore or a less positive food (meatball or food pellet) or social reward (familiar person or less familiar person).That all the stimuli were positive and of different reward value was confirmed in a runway motivation test.Dogs were tested individually while standing facing a display theatre where the different stimuli could beshown by lifting a shutter. The dogs approached and remained voluntarily in the test system. They were testedin four sessions (of 20 s each) for each of the four stimuli. A test session consisted of four presentation phases(1st exposure to stimulus, post exposure, 2nd exposure, and access to reward). Heart rate (HR) and heart ratevariability (HRV) responses were recorded during testing in the experimental room and also when lying restingin a quiet familiar room. A newmethod of ‘stitching’ short periods of HRV data together was used in the analysis.When testing different stimuli, no significant differenceswere observed in HR and LF:HF ratio (relative power inlow frequency (LF) and the high-frequency (HF) range), implying that the sympathetic tone was activated similarlyfor all the stimuli and may suggest that dogs were in a state of positive arousal. A decrease of HF was associatedwith the meatball stimulus compared to the food pellet and the reward phase (interacting with the personor eating the food) was associated with a decrease in HF and RMSSD (root mean square of successive differencesof inter-beat intervals) compared to the preceding phase (looking at the person or food). This suggests that parasympatheticdeactivation is associated with a more positive emotional state in the dog. A similar reduction in HFandRMSSDwas found in the test situation compared to the resting situation. This is congruentwith the expectedautonomic effects related to postural shift i.e. sympathetic activation and parasympathetic withdrawal, duringstanding versus lying, but it cannot explain the parasympathetic deactivation in response to the more positivestimuli since the dogs were always standing in the test situation.Wediscuss the systematic pattern of responses,which support that increased HRand LF:HF ratio are associatedwithemotional arousal, but add the newproposalthat a combined decrease inRMSSD and HFmay reflect a more positively valencedemotional state evenwhen anindividual is already in a positive psychological state.

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  • 38.
    Österman, Hanna
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Lindgren, Isa
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Lindström, Tom
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Chronic hypoxia during development does not trigger pathologic remodeling of the chicken embryonic heart but reduces cardiomyocyte number2015In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 309, no 10, p. R1204-R1214Article in journal (Refereed)
    Abstract [en]

    Fetal growth restriction programs an increased risk of cardiovascular disease in adulthood, but the actual mechanisms of this developmental programming are not fully understood. Previous studies in mammalian models suggest that hearts of growth-restricted fetuses have reduced cardiomyocyte number due to reduced proliferation and premature cardiomyocyte maturation. Chicken embryos incubated under chronic hypoxia are also growth-restricted, have smaller hearts, and show signs of cardiac insufficiency posthatching. The aim of the present study was to investigate how chronic hypoxia (14% O-2) during development affects cardiomyocyte mass and how myocardial structure is altered. Hypoxic incubation reproduced the well-characterized embryonic growth restriction and an increased ventricle-to-body mass ratio (at E11, E15, E17, and E19) with reduced absolute heart mass only at E19. Cell density, apoptosis, and cardiomyocyte size were insensitive to hypoxia at E15 and E19, and no signs of ventricular wall remodeling or myocardial fibrosis were detected. Bayesian modeling provided strong support for hypoxia affecting absolute mass and proliferation rates at E15, indicating that the growth impairment, at least partly, occurs earlier in development. Neither E15 nor E19 hearts contained binucleated cardiomyocytes, indicating that fetal hypoxia does not trigger early maturation of cardiomyocytes in the chicken, which contrasts with previous results from hypoxic rat pups. In conclusion, prenatal hypoxia in the chick embryo results in a reduction in the number of cardiomyocytes without inducing ventricular remodeling, cell hypertrophy, or premature cardiomyocyte maturation.

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