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  • 1.
    Bjarnegård, Niclas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences.
    Ahlgren, AR
    Sonesson, B
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Physiology . Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    The effect of sympathetic stimulation on proximal brachial artery mechanics in humans - differential behaviour within the length of the brachial artery?2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 182, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Aims: The mechanical properties of arteries play a major role in the regulation of blood pressure and cardiac performance. The effect of sympathetic stimulation on the mechanical properties of the proximal brachial artery was analysed in 18 healthy volunteers, nine young (25 +/- 2 years) and nine elderly (69 +/- 2 years). Methods: A non-invasive ultrasonic echo-tracking system for measurement of systolic/diastolic variation of the proximal brachial artery diameter in combination with intra-arterial pressure measurements was used to determine wall mechanics. The pressure-diameter (P-D) relationship, distensibility coefficient (DC), compliance coefficient (CC) and stiffness(beta) were obtained at rest and during sympathetic stimulation induced by lower body negative pressure (LBNP). Results: The peripheral vascular resistance increased by 100 and 72%, respectively in the young and elderly during LBNP (P < 0.001). Simultaneously, the mechanical properties of the proximal brachial artery remained unaltered, as estimated from both P-D relationship and stiffness in young (beta-index rest: 5.2 +/- 0.9, LBNP: 5.5 +/- 1.3, NS) as well as elderly (beta-index rest: 13.6 +/- 4.6, LBNP: 16.1 +/- 4.7, NS). Conclusions: LBNP-induced sympathetic activation does not change proximal brachial artery mechanics, in contrast to earlier reports on the muscular distal brachial artery. This may imply that the transition between elastic and muscular artery behaviour is within the length of the brachial artery, where the site of transition from elastic to muscular wall structure needs to be specified in future studies.

  • 2.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Rydén Ahlgren, Å.
    Department of Clinical Physiology, Malmö University Hospital, Malmö, Sweden .
    Sonesson, B.
    Department of Vascular Surgery, Malmö University Hospital, Malmö, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    The effect of sympathetic stimulation on proximal brachial artery mechanics in humans: differential behaviour within the length of the brachial artery2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 182, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Aims: The mechanical properties of arteries play a major role in the regulation of blood pressure and cardiac performance. The effect of sympathetic stimulation on the mechanical properties of the proximal brachial artery was analysed in 18 healthy volunteers, nine young (25 ± 2 years) and nine elderly (69 ± 2 years).

    Methods: A non-invasive ultrasonic echo-tracking system for measurement of systolic/diastolic variation of the proximal brachial artery diameter in combination with intra-arterial pressure measurements was used to determine wall mechanics. The pressure–diameter (P–D) relationship, distensibility coefficient (DC), compliance coefficient (CC) and stiffness(β) were obtained at rest and during sympathetic stimulation induced by lower body negative pressure (LBNP).

    Results: The peripheral vascular resistance increased by 100 and 72%, respectively in the young and elderly during LBNP (P < 0.001). Simultaneously, the mechanical properties of the proximal brachial artery remained unaltered, as estimated from both P–D relationship and stiffness in young (β-index rest: 5.2 ± 0.9, LBNP: 5.5 ± 1.3, NS) as well as elderly (β-index rest: 13.6 ± 4.6, LBNP: 16.1 ± 4.7, NS).

    Conclusions: LBNP-induced sympathetic activation does not change proximal brachial artery mechanics, in contrast to earlier reports on the muscular distal brachial artery. This may imply that the transition between elastic and muscular artery behaviour is within the length of the brachial artery, where the site of transition from elastic to muscular wall structure needs to be specified in future studies.

  • 3.
    Björnström, Karin
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Sjölander, Anita
    Division of Experimental Pathology, Lund University, Malmö, Sweden.
    Schippert, Åsa
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    A tyrosine kinase regulates propofol-induced modulation of the β-subunit of the GABAA receptor and release of intracellular calcium in cortical rat neurones2002In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 175, no 3, p. 227-235Article in journal (Refereed)
    Abstract [en]

    Propofol, an intravenous anaesthetic, has been shown to interact with the β-subunit of the γ-amino butyric acidA (GABAA) receptor and also to cause changes in [Ca2+]i. The GABAA receptor, a suggested target for anaesthetics, is known to be regulated by kinases. We have investigated if tyrosine kinase is involved in the intracellular signal system used by propofol to cause anaesthesia. We used primary cell cultured neurones from newborn rats, pre-incubated with or without a tyrosine kinase inhibitor before propofol stimulation. The effect of propofol on tyrosine phosphorylation and changes in [Ca2+]i were investigated. Propofol (3 μg mL−1, 16.8 μM) increased intracellular calcium levels by 122 ± 34% (mean ± SEM) when applied to neurones in calcium free medium. This rise in [Ca2+]i was lowered by 68% when the cells were pre-incubated with the tyrosine kinase inhibitor herbimycin A before exposure to propofol (P < 0.05). Propofol caused an increase (33 ± 10%) in tyrosine phosphorylation, with maximum at 120 s, of the β-subunit of the GABAA-receptor. This tyrosine phosphorylation was decreased after pre-treatment with herbimycin A (44 ± 7%, P < 0.05), and was not affected by the absence of exogenous calcium in the medium. Tyrosine kinase participates in the propofol signalling system by inducing the release of calcium from intracellular stores and by modulating the β-subunit of the GABAA-receptor.

  • 4. Crenshaw, A.G.
    et al.
    Gerdle, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Heiden, M.
    Karlsson, S.
    Fridén, J.
    Intramuscular pressure and electromyographic responses of the vastus lateralis muscle during repeated maximal isokinetic knee extensions.2000In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 170, p. 119-126Article in journal (Refereed)
  • 5. Erga, KS
    et al.
    Peen, E
    Eneström, S
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Reed, RK
    Effects of lactoferrin on rat dermal interstitial fluid pressure (Pif) and in vitro endothelial barrier function2001In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 171, no 4, p. 419-425Article in journal (Refereed)
    Abstract [en]

    We recently demonstrated that intravenous (i.v.) injection of the iron-binding protein lactoferrin (Lf) followed by antilactoferrin (aLf) antibodies or iron-saturated Lf alone increased albumin extravasation in vivo in several tissues including skin. Increased driving pressure for blood-tissue exchange or direct effects of Lf on the endothelial barrier are possible mechanisms. We therefore, firstly, measured interstitial fluid pressure (Pif) in dermis of rats given 1 mg Lf i.v. followed 30 min later by aLf or saline and circulatory arrest 1 or 5 min thereafter and compared with controls. Secondly, transmonolayer passage of Evans blue labelled albumin (EB-albumin) was evaluated in porcine pulmonary artery endothelial cells exposed to iron-free or iron-saturated Lf (both 100 ╡g mL-1) in the absence and presence of 0.5 mM hydrogen peroxide. Pif increased significantly at 11-30 min following Lf to +2.1 ▒ 0.3 and +1.7 ▒ 0.2 mmHg at 11-20 and 21-30 min, respectively, compared with +0.1 ▒ 0.2 mmHg before Lf (P < 0.05, n = 25). Endothelial transmonolayer passage of EB-albumin during 3 h was not affected by iron-free or iron-saturated Lf neither in the absence nor presence of hydrogen peroxide that increased passage 3.5 times compared with controls. In conclusion, Lf-induced increase in albumin extravasation in rat skin is not explained by changes in Pif (because Lf raised Pif significantly) or direct effects of Lf on the endothelial barrier.

  • 6.
    Fridberger, Anders
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    van Maarseveen, J.
    Rijksuniversiteit Groningen, the Netherlands.
    Scarfone, E.
    Université de Montpellier II, France.
    Ulfendahl, M.
    Karolinska Institutet, Stockholm, Sweden.
    Flock, B.
    Karolinska Institutet, Stockholm, Sweden.
    Flock, A.
    Karolinska Institutet, Stockholm, Sweden.
    Pressure-induced basilar membrane position shifts and the stimulus-evoked potentials in the low-frequency region of the guinea pig cochlea1997In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 161, no 2, p. 239-252Article in journal (Refereed)
    Abstract [en]

    We have used the guinea pig isolated temporal bone preparation to investigate changes in the non-linear properties of the tone-evoked cochlear potentials during reversible step displacements of the basilar membrane towards either the scala tympani or the scala vestibuli. The position shifts were produced by changing the hydrostatic pressure in the scala tympani. The pressures involved were calculated from measurements of the fluid flow through the system, and the cochlear DC impedance calculated (1.5 x 10(11) kg m-4 s-1, n = 10). Confocal microscopic visualization of the organ of Corti showed that pressure increases in the scala tympani caused alterations of the position of the reticular lamina and stereocilia bundles. For low pressures, there was a sigmoidal relation between the DC pressure applied to the scala tympani (and thus the position shift of the organ of Corti) and the amplitude of the summating potential. The cochlear microphonic potential also showed a pronounced dependence on the applied pressure: pressure changes altered the amplitude of the fundamental as well as its harmonics. In addition, the sound pressure level at which the responses began to saturate was increased, implying a transition towards a linear behaviour. An increase of the phase lag of the cochlear microphonic potential was seen when the basilar membrane was shifted towards the scala vestibuli. We have also measured the intracochlear DC pressure using piezoresistive pressure transducers. The results are discussed in terms of changes in the non-linear properties of cochlear transduction. In addition, the implications of these results for the pathophysiology and diagnosis of Meniérè's disease are discussed.

  • 7.
    Golster, Helena
    et al.
    Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Thulesius, Olav
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Nilsson, G.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Heterogeneous blood flow response in the foot on dependency, assessed by laser Doppler perfusion imaging1997In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 159, no 2, p. 101-106Article in journal (Refereed)
    Abstract [en]

    The exact nature of the decrease in foot skin blood flow seen after a change in posture remains unsettled. This mechanism has previously been examined by non-invasive techniques such as the laser Doppler perfusion monitor (laser Doppler flowmetry). Taking into account the shortcomings of laser Doppler perfusion monitoring when applied to the determination of skin blood flow, which normally shows substantial heterogeneity, we have applied an emerging technology, the laser Doppler perfusion imager (LDPI). This technique provides a more comprehensive picture of the blood flow distribution in the skin, as it maps skin blood flow over a surface area (120×120 mm, 4096 measurement sites). It was used to examine if the reduction in tissue perfusion or the alterations in flow distributions seen after a change in posture (supine to dependency) could be fully explained by an increase in venous pressure (venous stasis of 50 mmHg) or if the data suggest a complementary mechanism.

    Skin blood flow of the forefoot decreased from 0.60 V (volt) (median) during rest to 0.40 and 0.38 V during venous stasis and dependency, respectively. Although almost identical median values were obtained during stasis and dependency, the flow distributions were different, with a loss of high flow values during venous stasis. Biological zero was 0.24 V.

    As the LDPI technique readily records skin perfusion during variations in venous stasis and posture, as well as information on flow distribution changes, it appears promising for future application in stimuli-response studies of skin blood flow. The difference in flow distribution seen between increased venous pressure and dependency suggests an additive regulatory mechanism to the veni-vasomotor reflex during a change in posture.

  • 8.
    Hedlund, Petter
    et al.
    Lund University Hospital.
    Alm, P.
    Lund University Hospital.
    Hedlund, H.
    Lund University Hospital.
    Larsson, B.
    Lund University Hospital.
    Andersson, K. E.
    Lund University Hospital.
    Localization and effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in human penile erectile tissue1994In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 150, no 1, p. 103-104Article in journal (Refereed)
  • 9.
    Hedlund, Petter
    et al.
    Lund University Hospital.
    Larsson, B.
    Lund University Hospital.
    Alm, P.
    Lund University Hospital.
    Andersson, K. E.
    Lund University Hospital.
    Distribution and function of nitric oxide-containing nerves in canine corpus cavernosum and spongiosum1995In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 155, no 4, p. 445-455Article in journal (Refereed)
    Abstract [en]

    Specimens of penile erectile tissue from the corpus cavernosum (CC) and corpus spongiosum (CS) of beagle dogs were investigated with reference to morphological and functional aspects of the nitric oxide (NO) system. Using immunohistochemistry, the smooth muscle bundles of the CC were found to contain a rich innervation, as seen by the pan-neuronal marker, protein gene product 9.5. A large number of nerves also stained positively for acetylcholine esterase. There was a moderate to rich supply of nerves containing NO synthase, which was frequently co-localized with vasoactive intestinal polypeptide. CS preparations from the proximal penis (the spongious bulb) had an innervation similar to that of the CC. However, CS preparations from the distal penis had a distinctly lower density of nerves than the proximal part, and spongious tissue from the glans penis was practically devoid of nerves. In isolated preparations of proximal and distal CC and CS, contracted by noradrenaline, electrical field stimulation (EFS) produced frequency-dependent relaxations. The responses were less pronounced in preparations from the distal penis, particularly in the CS. Pre-treatment with the NO-synthesis inhibitor NG-nitro-L-arginine abolished all relaxations. Carbachol effectively relaxed noradrenaline-contracted strips. The responses were similar in proximal preparations from the CC and CS, and significantly less pronounced in strips from the distal penis. NG-nitro-L-arginine significantly reduced the relaxant effect of carbachol. Preparations of spongious tissue from the glans penis did not react to high potassium solution, addition of noradrenaline, or EFS. The results demonstrate regional differences within the CS, both in innervation and functional responses.

  • 10.
    Kimme, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Gustafsson, U.
    Linköping University, Faculty of Health Sciences.
    Sollev, A.
    Department of Anaesthesiology, Karolinska Hospital, Stockholm, Sweden.
    Nilsson, G.
    Department of Biomedical Engineering, Linköping University, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Cerebral blood flow of the exposed brain surface measured by laser Doppler perfusion imaging1997In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 159, no 1, p. 15-22Article in journal (Refereed)
    Abstract [en]

    A novel application of laser Doppler flowmetry (LDF), laser Doppler perfusion imaging (LDPI), was used to study cerebral cortical blood flow (CBFcortex). In contrast to the conventional laser Doppler perfusion monitor, LDPI creates two-dimensional maps of the tissue perfusion in a well defined area of up to 120×120 mm comprising 4096 measurement points. Measurements of CBFcortex were made through an optically transparent polyester film applied to a cranial window preparation in ventilated anaesthetized pigs. Temporal and spatial heterogeneity in CBFcortex were visualized by LDPI during provocations which are known to alter CBF (varying arterial PCO2 or MABP, or infusion of adenosine at constant MABP (concomitant angiotensin administration) or by hyperoxemia). During hypercapnia the recorded CBFcortex increased homogeneously. The adenosine-mediated increase in recorded CBFcortex was concentrated on the lower flow interval, as was the hyperoxemia-caused decline. At decreasing MABP the autoregulatory threshold was found to vary locally within the cortex. The results suggest that LDPI, apart from detecting localized changes in CBFcortex, also visualizes flow changes within different vascular segments. Together with the practical advantages of the system, i.e. not necessitating direct contact with the tissues, this feature makes the technique suitable for studies of CBFcortex distributions.

  • 11.
    Kimme, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Ledin, Torbjörn
    Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Cortical blood flow autoregulation revisited using laser Doppler perfusion imaging2002In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 176, no 4, p. 255-262Article in journal (Refereed)
    Abstract [en]

    Methods of laser Doppler perfusion monitoring (LDPM) and imaging (LDPI) have been validated and found useful for measurements of brain blood flow in several studies. The present work was undertaken to examine the cortical blood flow autoregulatory phenomenon as it has lately been questioned and claimed to be method-dependent and related to sample volume. Spatial variations in cerebral cortical blood flow (CBFcortex) in the pressure range 20–140 mmHg (static cerebral autoregulation; caval block/angiotensin infusion) were studied in six mechanically ventilated (hypocapnic, normocapnic and hypercapnic) pigs anaesthetized with propofol and fentanyl. Although the cortical blood flow values sampled were highly heterogeneously distributed, they were strongly pressure-dependent as well as CO2-dependent (P < 0.001). A cumulative cerebral blood flow (CBF)–pressure (MAP) plot comprising all values obtained indicated a pressure range between 70 and 120 mmHg where CBF remained almost constant. However, at the local level in the cortex (mm2) the same type of ‘classic’ autoregulatory flow : pressure graphs (FPG) were found in only a few of the cases of the cortical areas examined (n = 96). Alterations in blood PaCO2 saturation did not affect the pressure : flow relationship at low perfusion pressures, whereas at normal or above normal values, and as anticipated, hypercapnia considerably increased CBF (P < 0.001). ‘Classic’ autoregulatory FPGs were found only when all values sampled were clustered together, whereas, as a new finding, data are presented indicating that autoregulatory capacity is lacking at the local level at some cortical surface areas.

  • 12.
    Nilsson, B
    et al.
    Department of Surgery, Sahlgrenska University Hospital, Göteborg.
    Valantinas, J
    Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
    Hedin, L
    Friman, S
    Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Göteborg,.
    Svanvik, Joar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Acetazolamide inhibits stimulated feline liver and gallbladder bicarbonate secretion2002In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 174, no 2, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Bile acidification is a key factor in preventing calcium carbonate precipitation and gallstone formation. Carbonic anhydrase II (CA II), that is inhibited by acetazolamide, plays a role in regulation of the acid-base balance in many tissues. This study examines the effect of acetazolamide on secretin- and vasoactive intestinal peptide (VIP)-stimulated gallbladder mucosal bicarbonate and acid secretion. Gallbladders in anaesthetized cats were perfused with a bicarbonate buffer bubbled with CO2 in air. In 20 experiments VIP (10 ╡g kg1 h1) and in 10 experiments secretin (4 ╡g kg1 h1) were infused continuously intravenous (i.v.). Hepatic bile and samples from the buffer before and after perfusion of the gallbladder were collected for calculation of ion and fluid transport. During basal conditions a continuous secretion of H+ by the gallbladder mucosa was seen. Intravenous infusion of vasoactive intestinal peptide (VIP) and secretin caused a secretion of bicarbonate from the gallbladder mucosa (P < 0.01). This secretion was reduced by intraluminal (i.l.) acetazolamide (P < 0.01). Bile flow was enhanced by infusion of VIP and secretin (P < 0.01) but this stimulated outflow was not affected by i.v. acetazolamide. The presence of CA II in the gallbladder was demonstrated by immunoblotting. Biliary CA activity has an important function in the regulation of VIP- and secretin-stimulated bicarbonate secretion across the gallbladder mucosa.

  • 13.
    Nyhlen, Kritsina
    et al.
    Department of Preclinical Research, Gambro Lundia AB, Lund, Sweden and Department of Nephrology, University Hospital, Lund, Sweden.
    Rippe, B.
    Department of Nephrology, University Hospital, Lund, Sweden.
    Hultkvist-Bengtsson, U.
    Department of Preclinical Research, Gambro Lundia AB, Lund, Sweden.
    An isolated blood-perfused guinea-pig lung model for simultaneous registration of haemodynamic, microvascular and respiratory variables1997In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 159, no 4, p. 293-302Article in journal (Refereed)
    Abstract [en]

    We have developed an optimized isolated lung perfusion system, which possesses several advantages. Firstly, studies of microvascular, respiratory, haematological and biochemical variables are combined in one model. Secondly, blood perfusion resulted in less oedema formation than buffer-perfused lungs, and high Po2 through ventilation with room air. Finally, data for the variables can be displayed, controlled and recorded in real time using a computerized system permitting subsequent processing (e.g. filtering without destroying original data). In this paper we discuss the basic behaviour of the model in terms of vascular resistance, vascular permeability, respiration and neutrophil sequestration. In addition, the effects of oleic acid, histamine and histamine receptor blockers were tested, and two methods of calculating vascular permeability are discussed. The way in which different anaesthetics affect the neutrophil content of lung tissue and blood was also investigated. In the model, oleic acid increased pulmonary vascular resistance and permeability, whereas histamine did not affect either permeability or the pre/postcapillary vascular resistance ratio. However, histamine receptor blockers increased this ratio, indicating that there was endogenous histamine release. The neutrophil content of the isolated lungs was increased, but this did not affect the variables measured. There was also accumulation of neutrophils in the lungs of blood donor animals, due to CO2 sedation. However, CO2 sedation proved to be superior to pentobarbital or ketamine anaesthesia in maintaining the levels of neutrophils circulating in the blood. In conclusion, this model seems to be sensitive and to yield reproducible results regarding the physiology or pathophysiology of the lung.

  • 14.
    Olsson, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-endokrin.
    Schwartz, G G
    Jonasson, Lena
    Linderfalk, C
    Are early clinical effects of cholesterol lowering mediated through effects on inflammation?2002In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 176, no 2, p. 147-150Article in journal (Refereed)
    Abstract [en]

    In a randomized, double-blind trial in 3086 patients with unstable angina pectoris or non-Q wave myocardial infarction we investigated if 80 mg of atorvastatin daily could improve outcome of cardiovascular events during a short period of time (16 weeks) compared with placebo. Baseline LDL cholesterol was 3.2 mmol L-1 (124 mg dL-1) and decreased by 40% to 1.9 mmol L-1 (72 mg dL-1) during atorvastatin treatment. The primary endpoint, which was a composite of death, non-fatal acute myocardial infarction, cardiac arrest with resuscitation or recurrent symptomatic myocardial ischaemia with objective evidence and requiring emergency rehospitalization occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group. The relative risk was 0.84 and 95% confidence interval was 0.70-1.00 (P = 0.048). Thus for patients with acute coronary syndromes, lipid-lowering therapy with high dose atorvastatin reduces recurrent ischaemic events in the short-term. A possible mechanism behind this rapid clinical effect induced by statin treatment is on inflammatory processes. Recent studies strongly suggest that acute T-cell activation is involved in the pathogenesis of unstable angina. In another study we investigated whether circulating T cells showed signs of activation in patients with stable angina pectoris (SA). Systemic venous blood samples were taken from 38 men with SA and 42 healthy controls. The T-cell receptor expression was assessed by three-colour flow cytometry using monoclonal antibodies against CD3, CD4, CD8, CD25 and human leucocyte antigen (HLA)-DR. Soluble interleukin-2 receptor (sIL-2R) was measured as the circulating form in serum. Levels of circulating CD3+ and CD4+ T cells tended to be higher in patients compared with controls. Patients were also shown to have a significant increase in CD4+ T cells expressing the activation markers CD25 (P < 0.05) and HLA-DR (P < 0.01). Furthermore, serum levels of sIL-2R were significantly higher (P < 0.001) in patients than in controls. We also observed that the T-cell response was more pronounced in patients without simvastatin treatment (n = 18) compared with simvastatin-treated patients (n = 20). In conclusion, our findings indicate that a continuous immune system activation takes place in patients with chronic angina pectoris, predominantly involving proliferation of CD4+ T cells. Statin treatment seems to be able to decrease this inflammatory response.

  • 15.
    Rousseau, Andreas
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Bak, Zoltan
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Janerot-Sjöberg, Birgitta
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Acute hyperoxaemia-induced effects on regional blood flow, oxygen consumption and central circulation in man2005In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 183, no 3, p. 231-240Article in journal (Refereed)
    Abstract [en]

    Aim:  Despite numerous in vitro and animal studies, circulatory effects and mechanisms responsible for the vasoconstriction seen during hyperoxaemia are yet to be ascertained. The present study set out to: (i) set up a non-invasive human model for the study of hyperoxia-induced cardiovascular effects, (ii) describe the dynamics of this effect and (iii) determine whether hyperoxaemia also, by vasoconstriction alters oxygen consumption (O2).

    Methods:  The study comprised four experiments (A, B, C and D) on healthy volunteers examined before, during and after 100% oxygen breathing. A: Blood flow (mL min−1·100 mL−1 tissue), venous occlusion plethysmography was assessed (n = 12). B: Blood flow was recorded with increasing transcutaneous oxygen tension (PtcO2) levels (dose–response) (n = 8). C: Heart rate (HR), stroke volume, cardiac output (CO) and systemic vascular resistance (SVR) was assessed using echocardiography (n = 8). D: O2 was measured using an open circuit technique when breathing an air-O2 mix (fraction of inhaled oxygen: FiO2 = 0.58) (n = 8).

    Results:  Calf blood flow decreased 30% during O2 breathing. The decrease in calf blood flow was found to be oxygen dose dependent. A similar magnitude, as for the peripheral circulation, of the effect on central parameters (HR/CO and SVR) and in the time relationship was noted. Hyperoxia did not change O2. An average of 207 (93) mL O2 per subject was washed in during the experiments.

    Conclusion:  This model appears suitable for the investigation of O2-related effects on the central and peripheral circulation in man. Our findings, based on a more comprehensive (central/peripheral circulation examination) evaluation than earlier made, suggest significant circulatory effects of hyperoxia. Further studies are warranted to elucidate the underlying mechanisms.

  • 16. Sandberg, M.
    et al.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Non-invasive measurement of blood flow in trapezius muscle - a methodological study2010In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201XArticle in journal (Refereed)
  • 17.
    Sandberg, Margareta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
    Zhang, Qiuxia
    Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Styf, Jorma
    Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Non-invasive monitoring of muscle blood perfusion by photoplethysmography: Evaluation of a new application2005In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 183, no 4, p. 335-343Article in journal (Refereed)
    Abstract [en]

    Aim: To evaluate a specially developed photoplethysmographic (PPG) technique, using green and near-infrared light sources, for simultaneous non-invasive monitoring of skin and muscle perfusion.

    Methods: Evaluation was based on assessments of changes in blood perfusion to various provocations, such as post-exercise hyperaemia and hyperaemia following the application of liniment. The deep penetrating feature of PPG was investigated by measurement of optical radiation inside the muscle. Simultaneous measurements using ultrasound Doppler and the new PPG application were performed to elucidate differences between the two methods. Specific problems related to the influence of skin temperature on blood flow were highlightened, as well.

    Results: Following static and dynamic contractions an immediate increase in muscle perfusion was shown, without increase in skin perfusion. Liniment application to the skin induced a rapid increase in skin perfusion, but not in muscle. Both similarities and differences in blood flow measured by Ultrasound Doppler and PPG were demonstrated. The radiant power measured inside the muscle, by use of an optical fibre, showed that the near-infrared light penetrates down to the vascular depth inside the muscle.

    Conclusions: The results of this study indicate the potentiality of the method for non-invasive measurement of local muscle perfusion, although some considerations still have to be accounted for, such as influence of temperature on blood perfusion.

  • 18.
    Sandstrom, Per
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Woods, C.M.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Brooke-Smith, M.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Saccone, G.T.P.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Toouli, J.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Svanvik, Joar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Highly selective iNOS inhibition and sphincter of Oddi motility in the Australian possum2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 181, no 3, p. 321-331Article in journal (Refereed)
    Abstract [en]

    Aim:  Inducible nitric oxide synthase (iNOS) plays a major role in acute pancreatitis. Selective inhibitors of iNOS are being developed as therapeutic agents. Sphincter of Oddi (SO) dysfunction may cause pancreatitis and nitric oxide is necessary for SO relaxation. A new highly selective iNOS inhibitor, AR-C102222AA (AR-C), is evaluated together with the established iNOS inhibitor, l-N6-(1-iminoethyl)lysine (l-NIL), and the selective neuronal nitric oxide synthase (nNOS) blocker S-methyl-l-thiocitrulline (SMTC).

    Methods:  In anaesthetized Australian Brush-tailed possums, the effect of topical, i.v. or i.a. administration of these drugs was evaluated on spontaneous SO motility, blood pressure (BP) and pancreatic vascular perfusion. SO motility was recorded by manometry and pancreatic vascular perfusion by laser Doppler fluxmetry. Also, the effect of SMTC and AR-C on electrical field stimulation (EFS)-induced non-cholinergic non-adrenergic (NANC) SO relaxation in vitro was evaluated.

    Results:  Infusion of AR-C (0.1–30 μmol kg−1) increased SO contraction frequency (P = 0.026) only at the two highest doses. l-NIL infusion (0.15 to 14.7 μmol kg−1) also increased SO contraction frequency at 8.8 μmol kg−1 (P < 0.05) and reduced SO contraction amplitude at the two highest doses (P < 0.05). SMTC injections (0.5 nmol–2.4 μmol) produced a dose-dependent increase in SO contraction frequency (P = 0.009), but no effect was seen on the other parameters. In vitro SMTC (40–400 μm) inhibited EFS-induced NANC relaxation in a dose-dependent manner (P < 0.0005). In contrast AR-C (10–500 μm) had no effect on EFS-induced NANC relaxation (P > 0.05).

    Conclusions:  At low doses, AR-C does not effect SO motility or EFS-induced NO mediated relaxation. However, high doses of AR-C and L-NIL in vivo influenced SO motility by inhibiting nNOS activity and these effects need be considered in relation to therapeutic doses of this agent.

  • 19.
    Sjöberg, Birgitta Janero
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Eidenvall, L
    Loyd, Dan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Wranne, Bengt
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Vascular characteristics influence the aortic ultrasound Doppler signal: computer and hydraulic model simulations.1993In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 147, no 3, p. 271-279Article in journal (Refereed)
    Abstract [en]

    There is an increasing demand for non-invasive methods for the assessment of left ventricular function. Ultrasound Doppler methods are promising, and the early systolic flow velocity signal immediately distal to the aortic valve has been used clinically for this purpose. However, the signal is influenced not only by left ventricular ejection but also by systemic vascular characteristics. Their relative contribution to the time-velocity signal has not been analysed in depth previously. A theoretical analysis, based on a three-element Windkessel model, neglecting peripheral outflow in early systole and assuming linear pressure rise, was therefore tested in computer and hydraulic model simulations where peripheral outflow was included. Significant changes in early aortic flow velocity parameters were found when vascular characteristics were altered. As predicted by the theory, with a standardized aortic valve area and aortic pressure change, the simulations confirmed that maximal flow velocity is related to compliance of the aorta and the large arteries, and that maximal acceleration is inversely related to the characteristic impedance of the aorta. Therefore, maximal velocity and acceleration can be used for assessment of left ventricular function only in situations where vascular characteristics can be considered relatively constant or where they can be estimated.

  • 20.
    Sjöberg, Folke
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Gustafsson, U
    Eintrei, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Specific blood flow reducing effects of hyperoxaemia on high flow capillaries in the pig brain.1999In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 165, p. 33-38Article in journal (Refereed)
  • 21.
    Støen, R.
    et al.
    Department of Pediatrics, University Hospital, Trondheim, Norway and Department of Physiology and Biomechanical Engineering, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
    Lossius, K.
    Department of Pediatrics, University Hospital, Trondheim, Norway and Department of Physiology and Biomechanical Engineering, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
    Asplund-Persson, Anna
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Karlsson, J.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Relative significance of the nitric oxide (NO)/cGMP pathway and K+ channel activation in endothelium-dependent vasodilation in the femoral artery of developing piglets2001In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 171, no 1, p. 29-35Article in journal (Refereed)
    Abstract [en]

    Mechanisms mediating endothelium-dependent vasodilation were investigated in femoral artery rings from <2-day-old (newborn) and 2-week-old piglets. Based on previous results we hypothesized an age difference in the relative contribution of nitric oxide(NO)-cyclic 3′,5′-guanosine monophosphate (cGMP) and K+ channel-activation to acetylcholine (ACh)-induced vasodilation. Changes in vascular tone were studied in organ baths in the absence or presence of NO synthase(NOS) inhibition or K+ channel blockade and the intra-arterial accumulation of cGMP in response to ACh was measured with radioimmunoassay (RIA). In control experiments, relaxant responses to ACh were equal in the two age groups. In the presence of the NOS-inhibitors N G-monomethyl-L-arginine acetate (L-NMMA; 100 μM) or NG-nitro-L-arginine (L-NOARG; 1–100 μM), however, relaxation was significantly more reduced in femoral artery rings from 2-week-old than from newborn, with lower pD2 values in the older age group. Inhibition of large (BKCa) conductance calcium-sensitive K+ channels with tetraethylammonium chloride (TEA; 1 mM), gave a significant rightward shift in the concentration-response curves to ACh which was of the same magnitude in both age groups. The ACh-induced vasodilation was abolished in both age groups by high K+ (20 mM) in combination with L-NOARG (100 μM). The relative increase in cGMP levels after addition of ACh (10 nM) was significantly larger in rings from newborn compared with 2-week-old piglets (12- vs. four-fold). In summary, sensitivity to NOS inhibition increased with age while the effect of K+ channel blockade with TEA was the same in femoral artery rings from newborn to 2-week-old piglets. Lower sensitivity to NOS inhibition and a larger increase in cGMP in response to ACh could indicate a higher efficacy of the NO/cGMP pathway in this vessel in the newborn piglet.

  • 22.
    Zhang, Q.
    et al.
    Dept. of Orthopaedics Sahlgrenska University Hospital.
    Andersson, G.
    Dept. of Orthopaedics Sahlgrenska University Hospital.
    Lindberg, Lars-Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Styf, J.
    Dept. of Orthopaedics Sahlgrenska University Hospital.
    Muscle blood flow in response to concentric muscular activity vs. passive venous compression2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 180, no 1, p. 57-62Article in journal (Refereed)
    Abstract [en]

    Aim: To measure muscle blood flow (MBF) using photoplethysmography (PPG) following concentric muscular activity of the leg (active treatment) or passive venous compression (passive treatment) with or without venous obstruction. Methods: In study A, blood flow in the anterior tibial muscle was measured in 15 healthy subjects with a mean age of 30 years. In study B, blood flow in the gastrocnemius muscle was measured in nine healthy subjects with a mean age of 34 years. Subjects performed concentric muscular activity in one leg. Passive venous compression by a venous foot pump was applied in the contralateral leg. Results: MBF increased significantly following concentric muscular activity, but not following passive venous compression. MBF decreased in both legs when venous obstruction, induced by a thigh tourniquet, was applied. However, MBF was significantly higher following concentric muscular activity than passive venous compression. Conclusion: We conclude that concentric muscular activity produces higher MBF values than passive venous compression.

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