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K Ytrehus

Publications and source records attributed to K Ytrehus.

At least 37 records · Page 2Linked to original sources
PubMed1997

Potassium channel blocker dofetilide does not abolish ischaemic preconditioning.

Ischaemic preconditioning (IP) is a powerful mechanism for infarct reduction. Enhanced K+ conductance and shortening of action potential duration in the early phase of the sustained ischaemic episode have been proposed as important factors in the IP mechanism for infarct reduction. We have investigated whether the potassium channel-blocking class III anti-arrhythmic agent dofetilide could abolish IP in an in situ rabbit heart infarct model. Dofetilide is a specific blocker of the delayed rectifier potassium channel and thus lengthens the action potential duration by reducing potassium conductance during repolarization. Anaesthetized, open-chest rabbits were subjected to 30 min of regional ischaemia and 180 min of reperfusion. The ischaemic risk zone was determined by fluorescent particles, and infarct size was determined by TTC staining. Three groups were investigated: control, ischaemic preconditioned (IP) and IP plus dofetilide-treated (IPdof). The preconditioning protocol was 5 min regional ischaemia and 10 min reperfusion. The IPdof group underwent the same preconditioning protocol but additionally received dofetilide 20 micrograms kg-1 i.v. during the first 2 min of the first reperfusion period. Compared to pre-drug values dofetilide increased monophasic action potential duration from 149.2 +/- 11.5 ms (n = 4) to 215.8 +/- 12.4 ms, supporting blockade of the delayed rectifier potassium channel. At the same time heart rate was decreased from 255.5 +/- 12.5 to 230.3 +/- 8.2. The results expressed as percent infarction of the risk zone +/- SEM for the different groups were as follows: control (n = 11), 42.4 +/- 7.1; IP (n = 6), 7.6 +/- 4.3 [symbol: see text]; IPdof (n = 7), 12.3 +/- 4.1 [symbol: see text] (*p < or = 0.05 vs. control). These results show that the potassium channel-blocking agent dofetilide given after the preconditioning ischaemia but before the sustained ischaemia does not abolish ischaemic preconditioning.

Animals↗
PubMed1996

Cardiac injury by activated leukocytes: effect of cyclooxygenase and lipoxygenase inhibition evaluated by electron microscopical morphometry.

Leukocytes can take part in an inflammatory response in the heart after myocardial infarction or cardio-thoracic surgery. To investigate the injurious mechanism of activated polymorphonuclear leukocytes (PMN), isolated rat hearts were perfused with phorbol 12-myristate 13-acetate (PMA) activated PMN (3 x 10(6)/ml) alone for 10 min, in combination with a mixture of oxygen free radical scavengers (superoxide dismutase+catalase+thiourea) or in combination with ibuprofen (IBU), a cyclooxygenase inhibitor or diethylcarbamazine (DCM), a lipoxygenase inhibitor or BW 755C, a dual inhibitor of cyclooxygenase and lipoxygenase and an oxygen free radical scavenger. After 30 min of recovery, the hearts were perfusion-fixed with glutaraldehyde for electron microscopical examination. Based on examination of 25 micrographs per heart obtained by a random sampling procedure and on morphometric methods, volume fractions (Vv) of mitochondria (mito), altered mitochondria (alt mito), myofilament, and cellular edema were measured as fractions of myocyte volume. The most important finding was that Vv(alt mito/myocyte) was 0.09 +/- 0.16 and 0.02 +/- 0.04 in the hearts receiving PMN+PMA alone and when scavengers were added, respectively, whilst no changes in mitochondrial ultrastructure was observed after addition of IBU, BW 755C or DCM. Vv(mito/myocyte) was for PMN+PMA alone: 0.33 +/- 0.04, +scavengers: 0.29 +/- 0.02 +IBU:0.29 +/- 0.02, +BW 755C: 0.23 +/- 0.03*, +DCM: 0.28 +/- 0.02 (mean +/- S.D., *P < 0.05 compared to PMN+PMA). Capillary wall volume (cap wall) as a fraction of the whole capillary was also quantified. Vv(cap wall/cap) was for PMN+PMA alone: 0.26 +/- 0.06, +scavengers: 0.22 +/- 0.03, +IBU: 0.19 +/- 0.04*, +BW755C: 0.21 +/- 0.03, +DCM: 0.15 +/- 0.04* (*P < 0.05). These results further strengthen the notion that activated PMN are intravascularly active. In addition to exerting a cardiodepressive effect the present study shows that activated PMN can induce structural changes in the heart through the combined action of oxygen free radicals and arachidonic acid metabolites.

Animals↗
PubMed1996

Bradykinin protects against infarction but does not mediate ischemic preconditioning in the isolated rat heart.

The aim of the study was to test if pre-ischemic treatment with bradykinin can protect against infarction in an isolated rat heart model of regional ischemia and reperfusion, and if any such protection is dependent upon activation of protein kinase C (PKC) or mediated through the nitric oxide (NO) pathway. We also investigated if bradykinin B2 receptor activation, alone or in combination with activation of adenosine receptors and alpha-adrenoceptors, are involved in the infarct size reducing effect of ischemic preconditioning. Buffer-perfused rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion. Risk zone was determined by fluorescent particles and infarct size by tetrazolium staining. Treatment with bradykinin (0.5 mumol/l) prior to ischemia significantly reduced infarct size in percentage of risk zone compared to control experiments (infarct size: 9.6 +/- 1.3% v 41.8 +/- 3.6%, P < 0.001). An inhibitor of NO synthesis, NOARG (100 mumol/l), did not interfere with the bradykinin induced protection (infarct size: 13.3 +/- 2.0%), while chelerythrine (2 mumol/l), an inhibitor of protein kinase C, reversed the effect of bradykinin (infarct size: 30.0 +/- 2.8%). NOARG did not influence infarct size in the control group (infarct size: 40.1 +/- 3.2%). Ischemic preconditioning with three cycles of 5 min global ischemia + 5 min reperfusion offered protection similar to bradykinin (infarct size: 8.4 +/- 2.0%). The bradykinin antagonist HOE 140 (1 mumol/l) reversed the effect of bradykinin (infarct size: 42.5 +/- 3.1%), but did not interfere with ischemic preconditioning (infarct size: 7.7 +/- 1.6%). Similarily, combined blockade of alpha-adrenergic, adenosine and bradykinin B2 receptors with p-benzamine (10 mumol/l). SPT (100 mumol/l) and HOE 140 did not interfere with ischemic preconditioning (infarct size: 7.8 +/- 1.1%). Thus, bradykinin can protect against infarction via protein kinase C, but independently of NO. A role for bradykinin in mediating ischemic preconditioning against infarction could not be demonstrated.

Animals↗
PubMed1996

Experimental hypothermia and rewarming: changes in mechanical function and metabolism of rat hearts.

Rewarming from accidental hypothermia is associated with fatal circulatory derangements. To investigate potential pathophysiological mechanisms involved, we examined heart function and metabolism in a rat model rewarmed after 4 h at 15-13 degrees C. Hypothermia resulted in a significant reduction of left ventricular (LV) systolic pressure, cardiac output, and heart rate, whereas stroke volume increased. The maximum rate of LV pressure rise decreased to 191 +/- 28 mmHg/s from a control value of 9,060 +/- 500 mmHg/s. Myocardial tissue content of ATP, ADP, and glycogen was significantly reduced, whereas lactate content remained unchanged. After rewarming, heart rate returned to control value, whereas LV systolic pressure, cardiac output, and stroke volume all remained significantly depressed. The posthypothermic maximum rate of LV pressure rise was 5,966 +/- 1.643 mmHg/s. The posthypothermic myocardial lactate content was significantly increased (to 13.3 +/- 3.2 nmol/mg from control value of 5.7 +/- 1.9 nmol/mg), and ATP and glycogen remained significantly lowered. Creatine phosphate or energy charge did not change significantly during the experiment. The finding of deteriorated myocardial mechanical function and a shift in energy metabolism shows that the heart could be an important target during hypothermia and rewarming in vivo, thus contributing to the development of a posthypothermic circulatory collapse.

Animals↗
PubMed1996

Changes in blood flow distribution and capillary function after deep hypothermia in rat.

The present experiments were carried out in the rat to investigate the peripheral vascular function prior to the development of posthypothermic circulatory collapse. In the first study, mean arterial blood pressure, heart rate, cardiac output, regional blood flow, and plasma volume of hypothermic (4 h, 15-13 degrees C) and rewarmed rats were compared with normothermic controls. In response to hypothermia, arterial blood pressure, heart rate, and cardiac output declined markedly. After rewarming, arterial blood pressure and heart rate recovered fully, whereas cardiac output was only 33 +/- 7% of the control value (p < 0.025). Tissue blood flow was markedly depressed during hypothermia (p < 0.025), except for the abdominal skin. After rewarming, blood flow in skeletal muscle returned to within control levels, whereas blood flow in internal organs remained low (p < 0.025 vs. control). Posthypothermic plasma volume was 77 +/- 3% of control (p < 0.05). In the second study, the transcapillary colloid osmotic pressure gradient (COPp-COPi) was calculated following measurement of colloid osmotic pressure in plasma (COPp) and interstitium (COPi) in prehypothermic, hypothermic, and posthypothermic rats. The posthypothermic value of COPp-COPi was 76 +/- 4% of the prehypothermic value (p < 0.05). In conclusion this study demonstrates that the reduced cardiac output in rewarmed rats is associated with an altered regional blood flow distribution compared with that of normal rats. Capillary integrity also seemed perturbed. Thus, changes in both control and function of the peripheral vasculature are important mechanisms in the development of a posthypothermic circulatory collapse.

Animals↗
PubMed1996

Endothelin-1 can reduce infarct size through protein kinase C and KATP channels in the isolated rat heart.

OBJECTIVE: Protection from ischaemic preconditioning (IP) is dependent on activation of protein kinase C (PKC), and preconditionings protection can be mimicked by stimulation of various membrane receptors which are known to activate PKC. It is well known that KATP channel activation is cardioprotective. We tested the hypothesis that preischaemic treatment with endothelin-1 (ET-1) can protect against infarction by a PKC-dependent mechanism and by activating KATP channels. METHODS: Buffer-perfused isolated rat hearts were subjected to 30 min regional ischaemia and 120 min reperfusion. Risk zone was determined by fluorescent particles, and infarct size by TTC staining. RESULTS: Treatment with ET-1 in a dose of 1 nM prior to ischaemia significantly reduced infarct size in % of the risk zone compared to the control group (infarct size: 14.1 +/- 2.6 vs. 41.9 +/- 3.4%), while ET-1 0.1 nM did not protect (infarct size: 40.9 +/- 3%). AS the protective dose of ET-1 resulted in a significant reduction of coronary flow, a control group with a similar preischaemic flow-reduction was included (infarct size: 48.1 +/- 4.2%). Both the nonselective ETA/ETB receptor antagonist bosentan (1 microM) and the ET(A)-receptor-selective antagonist BQ 123 (2 microM) abolished protection from ET-1 (infarct size: 43.3 +/- 3.5 and 41.3 +/- 3.3%, respectively), as did the PKC inhibitor chelerythrine (2 microM) (infarct size: 41.1 +/- 5.2%) and the KATP blocker 5-hydroxydecanoate (infarct size: 41.7 +/- 2.9%). None of the ET receptor antagonists bosentan and BQ-123 influenced infarct size alone (infarct size: 42.7 +/- 2.5 and 41.3 +/- 3.3%, respectively). IP, similarly to ET-1, reduced infarct size (infarct size: 6.1 +/- 1.4%), but the nonselective ET receptor antagonist bosentan did not interfere with preconditioning's protection (infarct size: 13.2 +/- 4.3%). CONCLUSIONS: ET-1 treatment prior to ischaemia can protect against infarction via ETA receptors by a PKC-dependent mechanism and by activating KATP channels, but ET does not mediate IP in the isolated rat heart.

Alkaloids↗
PubMed1995

Inhibition of sodium-hydrogen exchange reduces infarct size in the isolated rat heart--a protective additive to ischaemic preconditioning.

OBJECTIVES: Inhibition of Na+/H+ exchange with amiloride analogues has been shown to protect the ischaemic and reperfused heart. The aim of this study was to examine if preischaemic or postischaemic treatment with the selective Na+/H+ exchange inhibitor ethyl-isopropyl amiloride (EIPA, 1 microM) influenced infarct size in an isolated rat heart model of regional ischaemia and reperfusion, and if any such protection was additive to the protection afforded by ischaemic preconditioning. METHODS: Langendorff perfused rat hearts were subjected to 30 or 45 min of regional ischaemia and 120 min of reperfusion. The risk zone was determined by fluorescent particles and infarct size was determined by staining with triphenyltetrazolium chloride. RESULTS: Treatment with EIPA for 20 min before 30 min regional ischaemia significantly reduced infarct size (in % of the risk zone) compared to untreated controls [3.1 (SEM 1.0)% v 38.1(5.8)%, P < 0.001], a protection similar to that afforded by ischaemic preconditioning [6.1(2.5)%]. Combination of preischaemic EIPA treatment and ischaemic preconditioning also reduced infarct size [5.2(2.0)%, P < 0.01 v control group]. When EIPA was added to the buffer only during the first 30 min of reperfusion, no protection was observed [infarct size = 37.8(5.8)%, NS v control group]. In order to clarify if the protection observed with EIPA treatment was additive to protection by ischaemic preconditioning, another set of experiments was performed. In these experiments regional ischaemia was extended to 45 min. Preischaemic EIPA treatment reduced infarct size also in this model compared to controls [15.3(2.9)% v 64.3(2.9)%, P < 0.001], as did ischaemic preconditioning [23.5(4.2)%, P < 0.001 v controls, NS v EIPA treated hearts]. Combination of ischaemic preconditioning and preischaemic EIPA treatment further reduced infarct size significantly [3.9(0.6)%, P < 0.05 v all other groups with 45 min regional ischaemia]. CONCLUSIONS: Inhibition of Na+/H+ exchange reduces infarct size in the isolated rat heart infarct model if the exchanger is inhibited during the ischaemic period, and this protection is additive to the protection afforded by ischaemic preconditioning.

Amiloride↗
PubMed1995

Ischaemic preconditioning is protein kinase C dependent but not through stimulation of alpha adrenergic or adenosine receptors in the isolated rat heart.

OBJECTIVE: The aim was (1) to clarify whether alpha adrenoceptor and adenosine receptor stimulation is involved in the anti-infarct effect of ischaemic preconditioning in the rat heart, and (2) to test the hypothesis that signal transduction through membrane bound protein kinase C is essential for the protection. METHODS: Isolated, buffer perfused rat hearts were subjected to 30 min of regional ischaemia and 120 min of reperfusion. The risk zone was determined by fluorescent particles, and infarct size was determined by staining with triphenyltetrazolium chloride. RESULTS: Ischaemic preconditioning with three cycles of 5 min ischaemia plus 5 min of reperfusion significantly reduced infarct size as compared to non-preconditioned group [4.5(SEM 0.6)% of the risk zone v 45.5(5.7)%, P < 0.001]. Blockade of alpha adrenoceptors alone and simultaneous blockade of alpha adrenoceptors with phenoxybenzamine (10 microM) and adenosine receptors with sulphophenyltheophylline (100 microM) did not prevent the protective effect of ischaemic preconditioning [infarct size = 2.4(0.4) and 5.6(1.9)% respectively, NS v the non-treated preconditioned group]. Blocking either the membrane binding of protein kinase C with polymyxin B (1 microM) or direct inhibition of protein kinase C activity with chelerythrine (2 microM) completely abolished the infarct size reducing effect of ischaemic preconditioning [32.4(3.3)% and 48.2(4.0)% respectively, P < 0.005 v non-treated preconditioned group: NS v the non-preconditioned group]. CONCLUSIONS: In the rat heart infarct model the protective effect of ischaemic preconditioning is not mediated through stimulation of alpha adrenoceptors alone or the combined stimulation of alpha adrenergic and adenosine receptors, and it is dependent on activation of membrane bound protein kinase C.

Alkaloids↗
PubMed1995

Hydrogen peroxide as a protective agent during reperfusion. A study in the isolated perfused rabbit heart subjected to regional ischemia.

In spite of extensive research during the last decade it has not been possible to prove that endogenously generated hydrogen peroxide or any reduced oxygen species reaches sufficient concentration during reperfusion after myocardial ischemia to contribute significantly to irreversible cell injury. In an attempt to further test this hypothesis we subjected isolated perfused rabbit hearts to 30 min regional ischemia followed by reperfusion and supplied hydrogen peroxide in low levels with or without catalase during the first 30 min of reperfusion and thereafter continued the reperfusion for a total of 120 min. Five different groups were studied: controls, and hearts supplied with 2 microM H2O2, 1 microM H2O2, 1 microM H2O2 + catalase (IU/l) or catalase alone in the initial part of the reperfusion. At the end of 120 min reperfusion, area at risk was measured with fluorescent particles and infarct zone size with tetrazolium staining. The results were: in the control group 32 +/- 5.0% of the risk zone infarcted, in the 2 microM H2O2 group 16.3 +/- 5.6% and in the 1 microM H2O2 group 6.9 +/- 0.8% (P < 0.05 compared to control). The reduction in infarct size was not present when catalase was added to the hydrogen peroxide-containing solution (26.4 +/- 4.5) or if catalase was present alone (22.9 +/- 1.8% infarction). In conclusion, hydrogen peroxide, 1 microM, protected the heart during reperfusion and reduced the amount of cell death after 120 min of reperfusion. The study demonstrated reduction or delay in infarction based only on treatment in the reperfusion period. The mechanism behind this protection remains to be determined.

Analysis of Variance↗
PubMed1994

Phospholipid peroxidation in isolated perfused rat hearts subjected to hypothermia followed by rewarming: inverse relation to loss of function.

In the present experimental study phospholipid peroxidation after hypothermia and rewarming was investigated in isolated buffer-perfused rat hearts. Stable normotherm perfusion (37 degrees C) for 20 min was followed by cooling to 14 degrees C, 4 h perfusion at 14 degrees C, and rewarming to 37 degrees C followed by 30 min normotherm perfusion. Seven hearts went through the whole protocol, whereas six hearts were subjected only to the initial stabilization period. Mechanical performance was measured by a balloon in the left ventricle (LV) permitting measurements of LV pressure and its derivatives. At the end of perfusion, hearts were freeze clamped in liquid nitrogen for phospholipid peroxidation measurements, phospholipid fatty acid composition, high-energy phosphate content (adenosine tri-, di-, and monophosphate and creatine phosphate), and tissue water content. After rewarming there was a significant reduction in mechanical performance and coronary flow. Tissue content of high-energy phosphates was decreased and tissue water content was increased. Levels of peroxidized polyunsaturated fatty acids (conjugated diens) in phospholipids and nonesterified fatty acids were not significantly changed (135.2 +/- 31.1 vs 74.3 +/- 7.6 nmol/g tissue dry wt and 1212 +/- 203 and 1685 +/- 197 nmol/g in control and rewarmed hearts. However, the amount of peroxidized polyunsaturated fatty acids in phospholipids expressed as a fraction of the phospholipids was significantly reduced by the cooling/rewarming procedure (1.28 +/- 0.22 vs 0.61 +/- 0.09 x 10(-3), P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Phospholipid peroxidation after 60 min of global ischaemia and 10 min of reperfusion. A study in the isolated rat heart.

Peroxidation of polyunsaturated fatty acids in cell membranes is thought to be a crucial factor in the cascade leading to reperfusion damage in the myocardium. However, some studies also describe increased lipid peroxidation in ischaemic tissue. The present study therefore examines phospholipid peroxidation after 60 min of global ischaemia and during the initial phase of reperfusion in isolated Langendorff-perfused rat hearts. Lipids were extracted from these hearts and separated into phospholipid, triglyceride and non-esterified fatty acid fractions. The phospholipid fraction was hydrolysed with phospholipase A2, and reverse-phase high performance liquid chromatography of the fatty acids derived from the phospholipids was performed. Peroxidized polyunsaturated fatty acids were separated from unchanged fatty acids and amounts of monohydroxy or monohydroperoxy isomers were quantified by measuring conjugated dienes by UV absorption (235 nm). Phospholipids from ischaemic as well as free-radical-exposed tissue contained increased levels of peroxidized polyunsaturated fatty acids (20.7 +/- 2.4 and 20.5 +/- 2.3 respectively, v 11.8 +/- 1.4 units/mg dry weight in controls). After 2-10 min of reperfusion, a significant increase in phospholipid peroxidation was no longer detected (12.5 +/- 1.2 units/mg). The amount and the composition of non-esterified fatty acids were examined by gas chromatography. Ischaemia significantly increased both the amount of non-esterified fatty acids (1.5 +/- 0.8 v 4.9 +/- 1.8 nmol/mg dry wt) as well as the percentage composed of arachidonic acid (3.4 +/- 3.2% v 7.4 +/- 1.4%). Fatty acid levels remained elevated during reperfusion (5.5 +/- 1.9 nmol/mg and 7.0 +/- 1.4%). In conclusion, our results have demonstrated that prolonged ischaemia alone caused phospholipid peroxidation as well as accumulation of non-esterified arachidonic acid. There was no sign of further phospholipid peroxidation during reperfusion.

Animals↗
PubMed1994

Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium.

We used three interventions to test critically the theory that ischemic preconditioning is the result of translocation of cytosolic protein kinase C (PKC) into the membranes where it can be activated. If that theory were true then kinase activity should not be necessary during the preconditioning ischemia and thus blocking kinase activity at this time should not block protection. Secondly, since most translocation processes in the cell are accomplished by cytoskeletal microtubules, disrupting them with colchicine should also block protection from preconditioning. Finally, translocating PKC by transient exposure to PMA, should still require adenosine receptor activation to reactivate the PKC pathway during the subsequent ischemia. Blocking kinase activity with staurosporine during a 30 min insult completely blocks protection in preconditioned hearts but when staurosporine treatment was confined to the preconditioning episode protection was not blocked in five of the eight hearts studied. Microtubule disruption with colchincine did block the protective effect of preconditioning (38.3 +/- 1.9% infarction v 40.6 +/- 4.1% in non-preconditioned). Colchicine had no effect on infarct size in the non-preconditioned group. Five min PMA treatment plus 10 min washout significantly limited infarct size in isolated rabbit hearts subjected to 30 min regional ischemia (5.9 +/- 1.1% v 31 +/- 3.5% infarction in control). PMA's protection was blocked by adding the adenosine receptor blocker, SPT, during the sustained ischemia (38.1 +/- 6.1% infarction). All three of these experiments strongly support the translocation theory of ischemic preconditioning.

Alkaloids↗
PubMed1994

Preconditioning protects ischemic rabbit heart by protein kinase C activation.

Myocardial protection in the rabbit induced by ischemic preconditioning is thought to be adenosine receptor linked, but the signaling pathway responsible for the protection has yet to be identified. This study tests whether protein kinase C could be involved. Either of two inhibitors of protein kinase C, staurosporine (50 micrograms/kg) or polymyxin B (24 mg/kg), were administered to rabbits subjected to 30 min regional myocardial ischemia followed by 180 min reperfusion. Half of the rabbits were preconditioned while the other half served as nonpreconditioned controls. Nonpreconditioned hearts without drug or treated with staurosporine or polymyxin B resulted in 37.8 +/- 3.1, 40.5 +/- 2.8, and 42.0 +/- 7.0% infarction of the risk zone, respectively. Preconditioning limited infarct size to 7.3 +/- 2.7%. Both inhibitors blocked protection in preconditioned hearts with 36.2 +/- 2.7 and 40.9 +/- 2.5% of the risk zone infarcted, respectively. Activation of protein kinase C with 4 beta-phorbol 12-myristate 13-acetate (PMA) or with 1-oleyl-2-acetyl glycerol (OAG) mimicked preconditioning in buffer-perfused hearts. PMA (0.01 nmol/min) or OAG (10 nmol/min) for 5 min was followed by 10 min of washout. Infarct size after 30 min regional ischemia was limited in the PMA and OAG groups (6.4 +/- 1.4 and 11.7 +/- 3.3 vs. 28.0 +/- 4.5% in untreated controls) and was equipotent with ischemic preconditioning (11.8 +/- 2.2%). Polymyxin B also blocked protection from ischemic preconditioning in the isolated heart (33.0 +/- 5.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1994

Rat and rabbit heart infarction: effects of anesthesia, perfusate, risk zone, and method of infarct sizing.

Rabbits and rats are becoming popular models for in vitro as well as in situ studies of myocardial infarction. In the present analysis we evaluated the results of several of our completed investigations and tested whether blood-free perfusate, anesthesia, or risk zone size affects infarction in these species. In addition, the influence of the method used for determining infarct size (histology or histochemistry) was examined in rabbits. All hearts experienced 30 min of regional ischemia followed by either 2-3 h of reperfusion in animals in which infarct size was assessed by staining with triphenyltetrazolium chloride or 72 h in those in which histological methods were used to measure infarct size. Eighteen rabbit and seven rat hearts perfused with Krebs buffer, seventeen open-chest rabbits, eight rats anesthetized with pentobarbital, and ten conscious rabbits were studied. Risk zone size measured with fluorescent particles was plotted against infarct size. Infarct size was linearly correlated with risk zone size and did not differ among models for each species. In rat hearts the regression line passed through the origin so that zero infarction occurred with zero risk zone size. However, in the rabbit heart there was no apparent infarction for risk zone sizes < 0.3 cm3. Although the relationship between risk zone and infarction was found to be remarkably independent of the model chosen, the nonzero intercept for the rabbit heart can be an important, previously unrecognized source of experimental variability when infarct size is expressed as a percentage of the risk zone.

Anesthesia↗
PubMed1994

Experimental hypothermia: effects of core cooling and rewarming on hemodynamics, coronary blood flow, and myocardial metabolism in dogs.

Conflicting results have been reported as to the extent that cardiovascular function can be reestablished after rewarming from hypothermia. We measured hemodynamic function, myocardial metabolism and tissue water content in dogs core-cooled to 25 degrees C and later rewarmed. At 25 degrees C left ventricular (LV) systolic pressure (LVSP) was 54% +/- 4%, maximum rate of LV pressure rise (LV dP/dtmax) 44% +/- 5%, aortic pressure (AOP) 50% +/- 6%, heart rate (HR) 40% +/- 0%, cardiac output (CO) 37% +/- 5%, myocardial blood flow (MBF) 34% +/- 5%, and myocardial oxygen consumption (MVO2) 8% +/- 1%, compared to precooling. Stroke volume (SV) and LV end-diastolic pressure (LVEDP) were unchanged. As normothermia (37 degrees C) was reestablished, the depression of cardiac function and myocardial metabolism remained the same as that at 25 degrees C: LVSP 71% +/- 6%, LV dP/dtmax 73% +/- 7%, SV 60% +/- 9%, AOP 70% +/- 6%, CO 57% +/- 9%, MBF 53% +/- 8%, and MVO2 44% +/- 8% HR, in contrast, recovered to precooling values. The arterial concentrations of glucose and free fatty acids (FFA) did not change significantly during the experimental period, whereas an increase in lactate of nonmyocardial origin appeared after rewarming. Increased myocardial contents of creatine phosphate and water were found during both hypothermia and rewarming. The present study demonstrates a persistent depression of cardiac function after hypothermia and rewarming in spite of adequate energy stores. Thus, a direct influence on myocardial contractile function by the cooling and rewarming process is suggested.

Adenosine Triphosphate↗
PubMed1994

Endothelin-1 causes accumulation of leukocytes in the pulmonary circulation.

We previously reported that the endothelin-1 (ET-1)-induced increase in microvascular permeability in isolated rat lungs required leukocytes in the perfusate. The present study examines whether intravenous administration of ET-1 in rats causes an inflammatory reaction in the lungs. Histological examination of the lung specimens 2 hr following ET-1 infusion showed adhesion of leukocytes to the vascular endothelium in pulmonary vessels and sequestration of leukocytes in the pulmonary capillaries. Microscopic examination of the bronchoalveolar lavage fluid revealed that leukocytes had migrated into the alveoli. Simultaneously a depletion of peripheral blood leukocytes was observed. These effects were reversible by 24 hr. Monitoring of systemic hemodynamic effects showed a continued reduced cardiac stroke volume and increasing heart rate after 2 hr. In isolated rat lungs, ET-1 caused a rapid increase in pulmonary artery pressure, pulmonary microvascular pressure, and edema formation. Compared with Krebs-albumin-perfused lungs, blood-perfusion accelerated the edemagenic effect of ET-1. ET-1 plays a role in the regulation of leukocyte-endothelial cell interactions in the pulmonary circulation. This has potential importance for the edemagenic effect of ET-1.

Animals↗
PubMed1993

[Ibsen and sunshine].

It is known that some people become depressed in winter, and that treatment with light can be effective in such cases. A reasonable explanation of this depression seems to be lack of sunshine. The connection may be that light possibly influences the secretion of certain amines in the brain. The author believes that Henrik Ibsen was among those who are more dependent than others on sunshine for optimal function. This may explain why his moving from often dark, cold and rainy Norway to warm, sunny Italy in 1864 meant so much to him. It was a dramatic event in his life and he used it in his writing, especially in the three plays: Emporer and Galilean, Ghosts and When We Dead Awaken. In each of these three plays, happiness in sunshine is used as a contrast to the sadder, dark and unhappy aspect of life. Ibsen, the earnest man and author was a sunshine poet. He really loved the sun, perhaps because he himself was among those who, without sun, become depressed and downhearted and loose their love of work.

Depression↗