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  • 1.
    Carlén, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Åström Aneq, Meriam
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Gustafsson, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    ST/HR variables in firefighter exercise ECG: relation to ischemic heart disease2019In: Physiological Reports, E-ISSN 2051-817X, Vol. 7, no 2, article id e13968Article in journal (Refereed)
    Abstract [en]

    Exercise electrocardiography (ExECG) is regularly performed by Swedish firefighters by law. Heart rate-corrected analysis of ST segment variables (ST/HR) has shown improved prediction of ischemic heart disease (IHD) compared to ST depression alone. This has not previously been extensively studied in asymptomatic persons with a low probability of IHD. We therefore evaluated the predictive performance of ST/HR analysis in firefighter ExECG. ExECG was studied in 521 male firefighters. During 8.4 ± 2.1 years, 2.3% (n = 12) were verified with IHD by catheterization or myocardial scintigraphy (age 51.5 ± 5.5 years) and were compared with firefighters without imaging proof of IHD (44.2 ± 10.1 years). The predictive value of ST depression, ST/HR index, ST/HR slope, and area and rotation of the ST/HR loop was calculated as age-adjusted odds ratios (OR), in 10 ECG leads. Predictive accuracy was analyzed with receiver operating characteristics (ROC) analysis. ST/HR index ≤-1.6 μV/bpm and ST/HR slope ≤-2.4 μV/bpm were associated with increased IHD risk in three individual leads (all OR > 1.0, P < 0.05). ST/HR loop area lower than the fifth percentile of non-IHD subjects indicated IHD risk in V4, V5, aVF, II, and -aVR (P < 0.05). ST depression ≤-0.1 mV was associated with IHD only in V4 (OR, 9.6, CI, 2.3-40.0). ROC analysis of each of these variables yielded areas under the curve of 0.72 or lower for all variables and leads. Clockwise-rotated ST/HR loops was associated with increased risk in most leads compared to counterclockwise rotation. The limited clinical value of ExECG in low-risk populations was emphasized, but if performed, ST/HR analysis should probably be given more importance.

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  • 2.
    He, Rebecca S. S.
    et al.
    Duke Univ, NC USA.
    De Ruiter, Stacy
    Calvin Univ, MI USA.
    Westover, Tristan
    Duke Univ, NC USA.
    Somarelli, Jason A.
    Duke Univ, NC USA.
    Blawas, Ashley M.
    Duke Univ, NC USA.
    Dayanidhi, Divya L.
    Duke Univ, NC USA.
    Singh, Ana
    Calvin Univ, MI USA.
    Steves, Benjamin
    Calvin Univ, MI USA.
    Driesinga, Samantha
    Calvin Univ, MI USA.
    Halsey, Lewis G.
    Univ Roehampton, England.
    Fahlman, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Fdn Oceanog Comunitat Valenciana, Spain; Kolmarden Wildlife Pk, Sweden.
    Allometric scaling of metabolic rate and cardiorespiratory variables in aquatic and terrestrial mammals2023In: Physiological Reports, E-ISSN 2051-817X, Vol. 11, no 11, article id e15698Article in journal (Refereed)
    Abstract [en]

    While basal metabolic rate (BMR) scales proportionally with body mass (M-b), it remains unclear whether the relationship differs between mammals from aquatic and terrestrial habitats. We hypothesized that differences in BMR allometry would be reflected in similar differences in scaling of O-2 delivery pathways through the cardiorespiratory system. We performed a comparative analysis of BMR across 63 mammalian species (20 aquatic, 43 terrestrial) with a M-b range from 10 kg to 5318 kg. Our results revealed elevated BMRs in small (&gt;10 kg and &lt;100 kg) aquatic mammals compared to small terrestrial mammals. The results demonstrated that minute ventilation, that is, tidal volume (V-T)center dot breathing frequency (f(R)), as well as cardiac output, that is, stroke volume center dot heart rate, do not differ between the two habitats. We found that the "aquatic breathing strategy", characterized by higher V-T and lower f(R) resulting in a more effective gas exchange, and by elevated blood hemoglobin concentrations resulting in a higher volume of O-2 for the same volume of blood, supported elevated metabolic requirements in aquatic mammals. The results from this study provide a possible explanation of how differences in gas exchange may serve energy demands in aquatic versus terrestrial mammals.

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  • 3.
    Iresjö, Britt‐Marie
    et al.
    Department of Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Wang, Wenhua
    Department of Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Nilsberth, Camilla
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Marianne
    Department of Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Lönnroth, Christina
    Department of Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Smedh, Ulrika
    Department of Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Food intake, tumor growth, and weight loss in EP2 receptor subtype knockout mice bearing PGE2-producing tumors2015In: Physiological Reports, E-ISSN 2051-817X, ISSN 2051-817X, Vol. 3, no 7, p. 1-7, article id e12441Article in journal (Refereed)
    Abstract [en]

    Previous studies in our laboratory have demonstrated that prostaglandin (PG) E2 is involved in anorexia/cachexia development in MCG 101 tumor‐bearing mice. In the present study, we investigate the role of PGE receptor subtype EP2 in the development of anorexia after MCG 101 implantation in wild‐type (EP2+/+) or EP2‐receptor knockout (EP2−/−) mice. Our results showed that host absence of EP2 receptors attenuated tumor growth and development of anorexia in tumor‐bearing EP2 knockout mice compared to tumor‐bearing wild‐type animals. Microarray profiling of the hypothalamus revealed a relative twofold change in expression of around 35 genes including mRNA transcripts coding for Phospholipase A2 and Prostaglandin D2 synthase (Ptgds) in EP2 receptor knockout mice compared to wild‐type mice. Prostaglandin D2 synthase levels were increased significantly in EP2 receptor knockouts, suggesting that improved food intake may depend on altered balance of prostaglandin production in hypothalamus since PGE2 and PGD2 display opposing effects in feeding control.

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  • 4.
    Kristenson, Karolina
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US. Region Östergötland, Heart Center, Department of Thoracic and Vascular Surgery.
    Gerring, Edvard
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Björnsson, Bergthor
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Hedman, Kristofer
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Peak oxygen uptake in combination with ventilatory efficiency improve risk stratification in major abdominal surgery2024In: Physiological Reports, E-ISSN 2051-817X, Vol. 12, no 1, article id e15904Article in journal (Refereed)
    Abstract [en]

    This pilot study aimed to evaluate if peak VO2 and ventilatory efficiency in combination would improve preoperative risk stratification beyond only relying on peak VO2. This was a single-center retrospective cohort study including all patients who underwent cardiopulmonary exercise testing (CPET) as part of preoperative risk evaluation before major upper abdominal surgery during years 2008-2021. The primary outcome was any major cardiopulmonary complication during hospitalization. Forty-nine patients had a preoperative CPET before decision to pursue to surgery (cancer in esophagus [n = 18], stomach [6], pancreas [16], or liver [9]). Twenty-five were selected for operation. Patients who suffered any major cardiopulmonary complication had lower ventilatory efficiency (i.e., higher VE/VCO2 slope, 37.3 vs. 29.7, p = 0.031) compared to those without complications. In patients with a low aerobic capacity (i.e., peak VO2 &lt; 20 mL/kg/min) and a VE/VCO2 slope &gt;= 39, 80% developed a major cardiopulmonary complication. In this pilot study of patients with preoperative CPET before major upper abdominal surgery, patients who experienced a major cardiopulmonary complication had significantly lower ventilatory efficiency compared to those who did not. A low aerobic capacity in combination with low ventilatory efficiency was associated with a very high risk (80%) of having a major cardiopulmonary complication.

  • 5.
    Laustsen, Christoffer
    et al.
    Department of Clinical Medicine, MR Research Centre, Aarhus University, Aarhus, Denmark.
    Lipsø, Kasper
    Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark Department of Electrical Engineering, Technical University of Denmark, Kgs. Lyngby, Denmark.
    Ostergaard, Jakob Appel
    Department of Endocrinology and Internal Medicine and Danish Diabetes Academy, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
    Nørregaard, Rikke
    Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
    Flyvbjerg, Allan
    Department of Endocrinology and Internal Medicine and Danish Diabetes Academy, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
    Pedersen, Michael
    Department of Clinical Medicine, MR Research Centre, Aarhus University, Aarhus, Denmark Comparative Medicine Lab, Aarhus University, Aarhus, Denmark.
    Palm, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
    Ardenkjær-Larsen, Jan Henrik
    Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark Department of Electrical Engineering, Technical University of Denmark, Kgs. Lyngby, Denmark GE Healthcare, Broendby, Denmark.
    Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney.2014In: Physiological Reports, E-ISSN 2051-817X, ISSN 2051-817X, Vol. 2, no 12Article in journal (Refereed)
    Abstract [en]

    Good glycemic control is crucial to prevent the onset and progression of late diabetic complications, but insulin treatment often fails to achieve normalization of glycemic control to the level seen in healthy controls. In fact, recent experimental studies indicate that insufficient treatment with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which did not restore glycemic control, to streptozotocin (STZ)-diabetic rats using noninvasive hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) and blood oxygenation level-dependent (BOLD) (1)H-MRI to determine renal metabolic flux and oxygen availability, respectively. Suboptimal insulin administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates. The results demonstrate the importance of tight glycemic control in insulinopenic diabetes, and that insulin, when administered insufficiently, adds an additional burden on top of poor glycemic control.

  • 6.
    Mandic, Mirko
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Forsgren, Mikael
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. AMRA Med AB, Linkoping, Sweden.
    Romu, Thobias
    AMRA Med AB, Linkoping, Sweden.
    Widholm, Per
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. AMRA Med AB, Linkoping, Sweden.
    Sundblad, Patrik
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Gustafsson, Thomas
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Rullman, Eric
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Interval-induced metabolic perturbation determines tissue fluid shifts into skeletal muscle2021In: Physiological Reports, E-ISSN 2051-817X, Vol. 9, no 7, article id e14841Article in journal (Refereed)
    Abstract [en]

    Intense interval exercise has proven to be as effective as traditional endurance exercise in improving maximal oxygen uptake. Shared by these two exercise regimes is an acute reduction in plasma volume, which is a suggested stimulus behind exercise-induced increases in blood volume and maximal oxygen uptake. This study aimed to link exercise-induced metabolic perturbation with volume shifts into skeletal muscle tissue. Ten healthy subjects (mean age 33 +/- 8 years, 5 males and 5 females) performed three 30 s all-out sprints on a cycle ergometer. Upon cessation of exercise magnetic resonance imaging, (31)Phosphorus magnetic resonance spectroscopy and blood samples were used to measure changes in muscle volume, intramuscular energy metabolites and plasma volume. Compared to pre-exercise, muscle volume increased from 1147.1 +/- 35.6 ml to 1283.3 +/- 11.0 ml 8 min post-exercise. At 30 min post-exercise, muscle volume was still higher than pre-exercise (1147.1 +/- 35.6 vs. 1222.2 +/- 6.8 ml). Plasma volume decreased by 16 +/- 3% immediately post-exercise and recovered back to - 5 +/- 6% after 30 min. Principal component analysis of exercise performance, muscle and plasma volume changes as well as changes in intramuscular energy metabolites showed generally strong correlations between metabolic and physiological variables. The strongest predictor for the volume shifts of muscle and plasma was the magnitude of glucose-6-phosphate accumulation post-exercise. Interval training leads to large metabolic and hemodynamic perturbations with accumulation of glucose-6-phosphate as a possible key event in the fluid flux between the vascular compartment and muscle tissue.

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  • 7.
    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.

  • 8.
    Tamás, Éva
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Decision support for assessment of left ventricular diastolic function2018In: Physiological Reports, E-ISSN 2051-817X, Vol. 6, no 16Article in journal (Refereed)
    Abstract [en]

    Echocardiographic assessment of the left ventricular diastolic function (LVDF), an integrated part of evaluation of left ventricular function is still a delicate task and is performed with substantial inter-rater variability. Therefore, we aimed to create and evaluate a guidelines-based automated decision support. An algorithm was created for a hierarchical analysis of LVDF based on variables as recommended by the latest guidelines. Age-adjusted normal ranges were pooled from previously published studies into an integrated reference table. For proof-of-concept, 20 echocardiographic examinations were analyzed offline by four experienced physicians with more than 10 years of echocardiographic experience. The first assessments were to be performed as they would be in the clinical practice. Six months later, the assessments were repeated based on the 2017 ASE/EACVI guidelines. The overall inter-rater agreement for the first clinical assessments was moderate, while the guidelines-based assessments had only fair inter-rater agreement. Both kinds of manual assessment had poor agreement with the standardized automated assessment algorithm of LVDF. In conclusion, the presented automated decision support for evaluation of diastolic LV function by Doppler echocardiography is mainly based on current guidelines involving multiple parameters in combination. Incorporating age dependency aspects in our program (available for use at https://liu.se/en/research/left-ventricular-diastolic-function-decision-support) enhances the accuracy of the evaluation and reduces variability in evaluation of LVDF. The large inter-rater variation in classification in this study also underscores the usefulness of tools to support a standardized evaluation.

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  • 9.
    von Gruenewaldt, Anna
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Nylander, Eva
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Hedman, Kristofer
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Classification and occurrence of an abnormal breathing pattern during cardiopulmonary exercise testing in subjects with persistent symptoms following COVID-19 disease2022In: Physiological Reports, E-ISSN 2051-817X, Vol. 10, no 4, article id e15197Article in journal (Refereed)
    Abstract [en]

    Reduced exercise capacity and several limiting symptoms during exercise have been reported following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. From clinical observations, we hypothesized that an abnormal breathing pattern (BrP) during exercise may be common in these patients and related to reduced exercise capacity. We aimed to (a) evaluate a method to classify the BrP as normal/abnormal or borderline in terms of inter-rater agreement; (b) determine the occurrence of an abnormal BrP in patients with post-COVID; and (c) compare characteristics of post-COVID patients with normal and abnormal BrP. In a retrospective, cross-sectional study of patients referred for CPET due to post-COVID April 2020-April 2021, we selected subjects without a history of intensive care and with available medical records. Three raters independently categorized patients BrP as normal, abnormal, or borderline, using four traditional CPET plots (respiratory exchange ratio, tidal volume over ventilation, ventilatory equivalent for oxygen, and ventilation over time). Out of 20 patients (11 male), 10 were categorized as having a normal, 7 an abnormal, and three a borderline BrP. Inter-rater agreement was good (Fleiss kappa: 0.66 [0.66-0.67]). Subjects with an abnormal BrP had lower peak ventilation, lower exercise capacity, similar ventilatory efficiency and a similar level of dyspnea at peak exercise, as did subjects with a normal BrP. Patients BrP was possible to classify with good agreement between observers. A third of patients had an abnormal BrP, associated with lower exercise capacity. which could possibly explain exercise related symptoms in some patients with post-COVID syndrome.

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