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K Ytrehus

Publications and source records attributed to K Ytrehus.

At least 19 recordsLinked to original sources
PubMed2006

Sustained anti-beta-adrenergic effect of melatonin in guinea pig heart papillary muscle.

OBJECTIVE: Anti-ss-adrenergic actions of several substances influence heart function significantly. The anti-ss-adrenergic effect of melatonin was investigated, with special attention to protein kinase C (PKC) and nitric oxide (NO). DESIGN: Guinea pig papillary muscles were exposed to melatonin (500 pM) for 15 min and 20 min washout. Contractile force was measured during a bolus of isoproterenol (300 nM) given before melatonin, at the end of melatonin-exposure and after washout. In separate experiments blockers of PKC, NO-synthase (NOS) and melatonin receptors were added, or forskolin (10 microM) substituted for isoproterenol. RESULTS: Melatonin significantly reduced the increase in contractile force in response to isoproterenol, both when present and after melatonin-washout. The reduction was unaffected by inhibition of PKC, while inhibition of melatonin receptors or NOS seemed to abolish the effect. Melatonin induced a sustained but not acute reduction of contractile force response with forskolin stimulation. This was abolished by NOS-inhibition. CONCLUSION: Receptor-mediated immediate and sustained anti-ss-adrenergic effects of melatonin were demonstrated in contractile function. A role for NO in the response was indicated, while a role for PKC was not verified.

Adrenergic beta-Antagonists↗
PubMed2004

Positive inotropic and sustained anti-beta-adrenergic effect of diadenosine pentaphosphate in human and guinea pig hearts. Role of dinucleotide receptors and adenosine receptors.

AIM: Diadenosine polyphosphates are present intracellularly and in extracellular fluid due to release from secretory vesicles in platelets, chromaffin cells and other cells. This study investigates effects of diadenosine pentaphosphate (AP5A) on heart muscle function. METHODS: Contractile force amplitude and action potential duration at 90% repolarization (APD90) were measured after challenge with AP5A 50 microm or isoproterenol 50-70 nM in guinea pig papillary muscles. Isoproterenol was given immediately after AP5A-exposure or after 45 min washout. AP5A was combined with antagonists to the purinergic P2 receptor (suramin 100 microm), the dinucleotide receptor [diinosine pentaphosphate 30 microm (IP5I)] or adenosine receptors [8-(P-sulfophenyl) theophylline 50 microm (8-SPT)]. RESULTS: Results are %-change (mean +/- SEM) from value before exposure. AP5A increased contractile force by 22 +/- 3%* (*P <0.05), and IP5I abolished this. AP5A prolonged APD90 by 7 +/- 2%*. AP5A significantly reduced response to isoproterenol acutely from 31 +/- 4* (controls) to 9 +/- 4% and after 45 min washout from 61 +/- 14* (controls) to 16 +/- 5%. 8-SPT abolished the sustained effect. Increase in contractile force by AP5A was confirmed in human atria trabecula preparations. CONCLUSION: AP5A increased contractile force and prolonged APD90. Contractile force increased by stimulation of the dinucleotide receptor in guinea pig myocardium. The sustained anti-beta-adrenergic effect of AP5A was due to adenosine receptor stimulation.

Action Potentials↗
PubMed2002

Adenosine induces prolonged anti-beta-adrenergic effects in guinea-pig papillary muscle.

A sustained anti-beta-adrenergic effect of adenosine has been reported. This study was initiated to investigate this topic and especially elucidate the role of protein kinase C (PKC). Contractile force amplitude and action potential duration at 90% repolarization (APD90) were measured in guinea-pig papillary muscles before and after 5 min challenge with 5 nm isoproterenol. Protocols contained 30 min exposure to the test agents adenosine 33 microm (ado), adenosine + PKC-inhibitor bisindolylmaleimide 20 nM (ado + BIM), PKC-activator 1,2-dioctanoyl-sn-glycerol 10 microm (DOG) and alpha-agonist phenylephrine 5 microm (phe). Isoproterenol was given at the end of test exposure and after 15 min washout. Results are mean +/- SEM of percentage-change, P < or = 0.05 considered significant and labelled *. The first isoproterenol challenge significantly increased contractile force (27 +/- 7%*) in the control group. Responses in the test groups were 2 +/- 4 (ado), 1 +/- 5 (ado + BIM), 14 +/- 4* (DOG), 0 +/- 2% (phe). After washout of adenosine, DOG and phenylephrine, isoproterenol induced 3 +/- 8 (ado), 23 +/- 5* (ado + BIM), 13 +/- 5* (DOG), 15 +/- 7% (phe) increase in test groups compared with 22 +/- 5%* increase in contractile force in the control group. After 45 min washout of adenosine the inotropic response was still significantly reduced compared with control (29 +/- 4 vs. 79 +/- 8%*). Isoproterenol stimulation shortened APD90 in controls at both time points (5 +/- 1%* and 4 +/- 1%*), with no significant shortening in test groups. Adenosine induces sustained anti-beta-adrenergic effects on contractile force as well as APD90. A role for PKC in signal transduction is supported with respect to contractile force.

Action Potentials↗
PubMed2000

The ischemic heart--experimental models.

Results obtained by experimental studies of the ischemic heart have been of tremendous importance for the understanding of physiology, biochemistry and lately also the molecular genetics of the heart. Experimental models in use for the study of the ischemic heart involve studies on the integrated organism, experiments with isolated hearts or multicellular preparation, and also studies of cells isolated from the heart. Regional ischemia in the anaesthetized animal has been a standard model. Knowledge about infarct size limitation as well as heart function in acute and chronic ischemia has been obtained based on experiments in a wide variety of species. The isolated perfused heart has been subjected to extensive use. As a result, the understanding of intracellular processes is constantly developing. Cell models and transgenic-mice models represent promising additions. Each model and each species has certain advantages and disadvantages. Variability in susceptibility towards ischemia and reperfusion is also present. The consequences of ischemia can be described as contractile dysfunction and stunning, arrhythmia and infarction each representing different endpoints of injury. The experimental model is also heavily dependent on the endpoint that is chosen for the study. Results obtained in one experimental model can, therefore, not be generalized into universal conclusions about the ischemic heart. With respect to the human and the disease caused by myocardial ischemia, fragments of knowledge put together from different types of experimental models create the background for successful design of potential treatment.

Animals↗
PubMed2000

5-HD abolishes ischemic preconditioning independently of monophasic action potential duration in the heart.

OBJECTIVE: Blocking of the KATP channel with either glibenclamide or 5-hydroxydecanoate (5-HD) has been shown to abolish the infarct reducing effect of ischemic preconditioning (IPC) in hearts from several species, but the results in rat and rabbit have been equivocal. In this study we investigated if 5-HD could abolish IPC in rat and rabbit and further if IPC or IPC + 5-HD were affecting action potential duration in the rabbit heart. METHODS: The rat hearts were isolated and retrogradely perfused on a Langendorff perfusion apparatus with Krebs-Henseleit buffer. The rabbit experiments were performed in an in situ model. Rat and rabbit hearts were subjected to 30 min regional ischemia by ligating a coronary artery followed by 120 min (rat) or 150 min (rabbit) of reperfusion. The preconditioning protocol was one or three cycles of 5 min ischemia plus 5 min reperfusion in the rat and one cycle of 5 min ischemia plus 10 min reperfusion in the rabbit. In the rat 5-HD was added to the reservoir before ischemic preconditioning in different concentrations, and in the rabbit 5-HD was given as a bolus 5 mg/kg intraventricularly 2 min before the preconditioning ischemia. In the rabbit epicardial monophasic action potential duration at 50 % repolarization (MAPD50) was measured at 1, 2 and 5 min in each of the ischemic periods using a contact pressure electrode. Infarcts were measured with tetrazolium staining and risk zone volumes with fluorescent microspheres. RESULTS: All data are presented as infarct size in % of risk zone volume (mean +/- SEM). In the rat 200 microM of 5-HD abolished the protective effect of one cycle of IPC (28.6 +/- 4.7 versus 8.4 +/- 0.8) and 500M of 5-HD abolished three cycles of IPC (50.7 +/- 7.8 versus 8.4 +/- 2.0). Control was 40.9 +/- 2.8. In the rabbit 5-HD abolished IPC (41.2 +/- 7.2 versus 8.1 +/- 3.2). Control was 53.5 +/- 12.4. MAPD50 were significantly more shortened compared to control at 1 and 2 min into the 30 min ischemia for the IPC and IPC+5-HD. CONCLUSIONS: We conclude that 5-HD abolishes ischemic preconditioning when given before the preconditioning ischemia in both rat and rabbit but does not abolish the ischemia induced shortening of the action potential duration in the rabbit; thus, a role for the mitochondrial KATP channel and not the sarcolemmal KATP channel in the protective mechanism behind IPC is probable.

Action Potentials↗
PubMed1999

Coronary endothelium-derived vasodilation during cooling and rewarming of the in situ heart.

The integrity of coronary vascular endothelial vasodilator function during core cooling and rewarming was investigated in a pentobarbital-anesthetized open-chest dog model. Vasodilator response was assessed as the change from baseline blood flow by injecting the endothelial-dependent vasodilator acetylcholine (ACh) (1.0 microg) or the endothelial-independent vasodilator nitroglycerin (NTG) (50 microg) into the left anterior descending (LAD) coronary artery. Change in blood flow was measured using a transit time ultrasonic volume flowmeter technique. During cooling and rewarming LAD blood flow was significantly decreased. After rewarming, aortic pressure was artificially elevated to reach control. This procedure restored heart work (LV-RPP, left ventricular rate pressure product) and coronary perfusion pressure, but LAD blood flow remained lowered. Ability to dilate the vascular bed supplied by LAD, after injections of ACh or NTG, was present both during cooling and rewarming. At 25 degrees C coronary blood flow (LAD) increased from 3 +/- 1 to 9 +/- 1 mL x min(-1) in response to both ACh and NTG. Posthypothermic blood flow increased from 7 +/- 1 to 19 +/- 2 and 20 +/- 3 mL x min(-1) in response to ACh and NTG, respectively. Measured as the percent change from baseline LAD blood flow, the response was not significantly different from the one obtained in prehypothermic hearts. In conclusion, coronary vasodilator function, both endothelium dependent and endothelium independent, is present but not maintained at the same level during cooling to 25 degrees C and rewarming. In spite of the deterioration of cardiac function, no selective defect in the endothelium-dependent response was detected, either during hypothermia or after rewarming.

Acetylcholine↗
PubMed1998

Changes in myocardial ultrastructure induced by cooling as well as rewarming.

The aim of the present study was to investigate if hypothermia and rewarming, without accompanying cardiac ischaemia or cardioplegia, causes myocardial damage. Anaesthetized rats were subjected to a cooling procedure (4 h at 15-13 degrees C) where spontaneous cardiac electromechanical activity was maintained, followed by rewarming. Control rats, hypothermic rats and posthypothermic rats were perfusion-fixed, the hearts removed and the ventricles examined using an electron microscope. Based on morphometric methodology volume fractions as well as absolute volumes of cellular and subcellular components of the ventricles were assessed. In hypothermic hearts capillary volume fraction was significantly decreased, which was probably due to a decrease in perfusion pressure. The cytosolic volume increased in both absolute values and as a fraction of the myocyte: from 25 +/- 11 in controls to 43 +/- 8 microliters and from 0.067 +/- 0.023 to 0.102 +/- 0.013, respectively. There was a corresponding relative decrease in the volume fraction of myofilaments from 0.598 +/- 0.030 to 0.548 +/- 0.024. In posthypothermic hearts significant tissue swelling was apparent, dominated by a significant increase in myocyte volume from 372 +/- 66 in controls to 522 +/- 166 microliters. Similar changes were measured in mitochondrial and cytosolic volumes. In conclusion, the myocardial ultrastructure was altered during hypothermia as well as after rewarming. Posthypothermic myocardium showed generalized cellular swelling and areas of cellular necrosis.

Animals↗
PubMed1998

Lipid peroxidation, arachidonic acid and products of the lipoxygenase pathway in ischaemic preconditioning of rat heart.

OBJECTIVE: Preconditioning with brief intermittent periods of ischaemia is known to provide protection against ischaemic injury. It has been suggested that myocardial ischaemia also activates phospholipase A2, which releases arachidonic acid from phospholipids. In the present study the possible role of phospholipid peroxidation, arachidonic acid and products of the lipoxygenase pathway in cellular mechanisms of ischaemic preconditioning was examined. METHODS: Isolated, buffer-perfused rat hearts were freeze-clamped at the end of preconditioning (a cycle of 5 min global ischaemia +5 min reperfusion) and at the end of 30 min global ischaemia and analysed for non-esterified fatty acids and fatty acids in the 2-position of phospholipid. In a separate set of experiments, hearts pretreated with a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), were subjected to 30 min regional ischaemia and 120 min reperfusion. Infarct size was determined by tetrazolium staining and the ischaemic risk zone with fluorescent particles. RESULTS: Myocardial levels of arachidonic as well as of linoleic and docosahexaenoic acid were significantly elevated by preconditioning. Also, the level of peroxidized polyunsaturated fatty acids (measured as hydroxy conjugated dienes) in myocardial phospholipid was significantly increased: 101.4 +/- 16.8 nmol/g versus 51.2 +/- 7.3 nmol/g tissue dw in the control group, p < 0.05. Pre-treatment of hearts with 5 microM NDGA blocked the infarct limiting effects of preconditioning: infarct size was 37.4 +/- 6.4% of risk zone in control, 9.0 +/- 0.9% in the preconditioning group and 27.7 +/- 3.8% in the preconditioning + NDGA group (p < 0.05 vs. i.p., n.s. vs. control). CONCLUSION: Our findings provide evidence for the involvement of phospholipase A2 and lipoxygenase derived lipid second messengers in ischaemic preconditioning of the isolated rat heart.

Analysis of Variance↗
PubMed1998

Left ventricular dysfunction following rewarming from experimental hypothermia.

This study was aimed at elucidating whether ventricular hypothermia-induced dysfunction persisting after rewarming the unsupported in situ dog heart could be characterized as a systolic, diastolic, or combined disturbance. Core temperature of 8 mongrel dogs was gradually lowered to 25 degreesC and returned to 37 degreesC over a period of 328 min. Systolic function was described by maximum rate of increase in left ventricular (LV) pressure (dP/dtmax), relative segment shortening (SS%), stroke volume (SV), and the load-independent contractility index, preload recruitable stroke work (PRSW). Diastolic function was described by the isovolumic relaxation constant (tau) and the LV wall stiffness constant (Kp). Compared with prehypothermic control, a significant decrease in LV functional variables was measured at 25 degreesC: dP/dtmax 2,180 +/- 158 vs. 760 +/- 78 mmHg/s, SS% 20.1 +/- 1.2 vs. 13.3 +/- 1.0%, SV 11.7 +/- 0.7 vs. 8.5 +/- 0.7 ml, PRSW 90.5 +/- 7.7 vs. 29.1 +/- 5.9 J/m. 10(-2), Kp 0.78 +/- 0.10 vs. 0.28 +/- 0.03 mm-1, and tau 78.5 +/- 3.7 vs. 25.8 +/- 1.6 ms. After rewarming, the significant depression of LV systolic variables observed at 25 degreesC persisted: dP/dtmax 1,241 +/- 108 mmHg/s, SS% 10.2 +/- 0.8 J, SV 7.3 +/- 0.4 ml, and PRSW 52.1 +/- 3.6 m. 10(-2), whereas the diastolic values of Kp and tau returned to control. Thus hypothermia induced a significant depression of both systolic and diastolic LV variables. After rewarming, diastolic LV function was restored, in contrast to the persistently depressed LV systolic function. These observations indicate that cooling induces more long-lasting effects on the excitation-contraction coupling and the actin-myosin interaction than on sarcoplasmic reticulum Ca2+ trapping dysfunction or interstitial fluid content, making posthypothermic LV dysfunction a systolic perturbation.

Animals↗
PubMed1998

Increase in leukotrienes in the coronary circulation by cooling: a study in the anesthetized dog.

Pentobarbital-anesthetized dogs were instrumented for hemodynamic measurements and cooled by heat exchange tubes. Through a catheter in the coronary sinus, blood samples were obtained and plasma leukotrienes measured using a high-pressure liquid chromatography technique. Hemodynamic function was significantly reduced during cooling, and during subsequent rewarming hemodynamic function was only partly restored. Leukotriene C4 and B4 were significantly increased at a body core temperature of 31 degrees C and 25 degrees C during cooling but not during rewarming (28 degrees C) and after rewarming (37 degrees C). This indicates that during decreasing body temperature elevated leukotriene levels may increase vascular permeability, inflammation, and vasoactivity and counteract temperature-dependent decrease in these functions. Disturbed microcirculation may thus diminish cardiac recovery during rewarming.

Animals↗
PubMed1998

Equal reduction in infarct size by ethylisopropyl-amiloride pretreatment and ischemic preconditioning in the in situ rabbit heart.

UNLABELLED: Inhibition of Na+/H+ exchange with amiloride analogues has been shown to provide functional protection during ischemia and reperfusion and to reduce infarct size in isolated rat hearts. In rat hearts, treatment with ethylisopropyl-amiloride (EIPA, a selective Na+/H- exchange inhibitor) was additive to the protection afforded by ischemic preconditioning. In addition, such compounds have been demonstrated to reduce infarct size in in situ rabbit hearts. The aim of the present study was to determine to what extent preischemic treatment with EIPA could reduce infarct size in an in situ rabbit model of regional ischemia and reperfusion. We also wished to determine if this effect was additive to the infarct reducing effect of ischemic preconditioning. Anaesthetized, open chest rabbits, were subjected to 45 min of regional ischemia and 150 min of reperfusion. The risk zone was determined by fluorescent particles and infarct size was determined by TTC staining. Four groups were investigated: control, ischemic preconditioned (IP) (5 min of ischemia followed by 10 min reperfusion), EIPA (0.65 mg/kg iv given preischemically) and EIPA + IP. The main results expressed as percent infarction of the risk zone +/- S.E.M. for the different groups were: control 59.2+/-3.3% (n = 6), IP 16.3+/-2.1% (n = 6) (p < 0.001 vs. control), EIPA 16.9+/-4.1% (n = 5) (p < 0.001 vs. control), EIPA + IP 22.5 +/-9.5% (n = 6) (p < 0.001 vs. control). IN CONCLUSION: EIPA, when administered prior to ischemia, caused a reduction in infarct size in the in situ rabbit heart which was similar to that seen with ischemic preconditioning, however, the effect was not additive to ischemic preconditioning.

Amiloride↗
PubMed1998

Mechanism of hypoxic preconditioning in guinea pig papillary muscles.

UNLABELLED: Brief ischemia or hypoxia has been found to protect the heart against subsequent long-lasting ischemia and to improve contractile dysfunction as well to reduce cell necrosis and the incidence of lethal arrhythmias. This phenomenon, termed preconditioning (PC) has been demonstrated in different species. However, little is known about PC in guinea pigs. Moreover, electrophysiological changes underlying protection have not been studied so far in conjuntion with force recovery in a setting of PC. The aim of the study was to study PC in a guinea pig papillary muscle, using recovery of contractility after long hypoxic challenge as the main end-point of protection, and to investigate concomitant electrophysiological alterations. In guinea pig papillary muscle preparations contracting isometrically (paced at 2 Hz), transmembrane action potentials (AP) and developed force (DF) were recorded by conventional microelectrode technique and a force transducer. In addition, effective refractory periods (ERP) were determined. Hypoxia was induced by superfusion with 100% N2 (pO2 < 5 kPa) and pacing at 3,3 Hz. In the control group, long hypoxia lasted for 45 min and was followed by 30 min reoxygenation. In the PC group, muscles were subjected to 5 min hypoxia followed by 10 min recovery prior to sustained hypoxia/reoxygenation. RESULTS: Long hypoxia induced a similar depression of DF in both, PC and control groups. However, a loss of contractile activity occured earlier in the PC group. AP duration and ERP decreased faster and were significantly shorter after PC. Upon reoxygenation, preconditioned muscles showed significantly better recovery of function (DF 86% of prehypoxic value vs. 36% in controls; p < 0,05). AP and ERP were completely restored in both, PC and control groups. Guinea pig papillary muscle can be preconditioned with a brief hypoxic challenge against contractile dysfunction upon long-lasting hypoxia/reoxygenation. Shortening of AP and loss of contractility occured more quickly during hypoxia and may participate in the protective effect of preconditioning. Possible mechanisms might involve facilitated opening of K(ATP)-dependent channels.

Action Potentials↗
PubMed1997

Low concentrations of hydrogen peroxide improve post-ischaemic metabolic and functional recovery in isolated perfused rat hearts.

The aim of the present study was to test the hypothesis that low concentrations of hydrogen peroxide (H2O2) have a beneficial effect on post-ischaemic myocardial recovery. Functional and metabolic measurements were performed in isolated buffer-perfused rat hearts exposed to 30 min perfusion with 0 (control group A), 25, 50, 100 or 200 microM H2O2 or 30 min global ischaemia followed by 30 min reperfusion with 0 (control group B), 25, 50 or 100 microM H2O2. Catalase (200 U/ml) was added as scavenger during reperfusion with 25 microM H2O2. Non-ischaemic perfusion: All concentrations of H2O2 induced an immediate vasodilatation, which was maintained in the 50 microM group, but it was followed by vasoconstriction in the 100 and 200 microM group. Left ventricular developed pressure (LVDP) was significantly increased at the end of perfusion in the 50 microM group compared to the control group. Exposure to 100 and 200 microM H2O2 significantly decreased LVDP and increased end-diastolic pressure. ATP was reduced in the 100 microM group. Post-ischaemic perfusion: Exposure to 25 microM H2O2 caused improved coronary flow during the first 20 min of reperfusion compared to the control group (accumulated coronary flow; 235.5 +/- 10.8 v 172.7 +/- 8.6 ml). LVDP was significantly higher in the 25 microM group compared to the control (59.8 +/- 10.2 v 22.1 +/- 7.3 mmHg), and end-diastolic pressure was significantly lower (32.1 +/- 19.6 v 78.8 +/- 2.2 mmHg) at the end of reperfusion. Improved recovery was not observed in the group exposed to 25 microM H2O2 plus catalase. Treatment with 25 microM H2O2 caused significantly improved recovery of tissue ATP and creatine phosphate. In conclusion, the present study showed that exposure to 25 microM H2O2 improved post-ischaemic recovery in hearts subjected to global ischaemia.

Animals↗
PubMed1997

Mepacrine protects the isolated rat heart during hypoxia and reoxygenation--but not by inhibition of phospholipase A2.

Mepacrine (quinacrine) has in a number of studies been shown to protect the heart from ischemic injury, a protection commonly claimed to be due to inhibition of phospholipase A2. The aim of the present study was to investigate the effect of mepacrine 1 microM on isolated, buffer perfused rat hearts subjected to 60 min hypoxia and 30 min reoxygenation. We also wanted to clarify whether any cardioprotective effect was due to inhibition of phospholipase A2 or to other effects of the drug. Mepacrine led to a substantial fall in left ventricular developed pressure (LVDP) and coronary flow (CF) during normoxic perfusion. Treated hearts showed less increase in LVEDP and less fall in LVDP during the hypoxic period, and significantly fewer hearts stopped beating compared to untreated controls. Release of CK during hypoxia and reoxygenation was reduced in treated hearts compared to controls (19.9 +/- 3.8 vs. 73.1 +/- 13.3 IU, p < 0.05). Lipid analyses of the myocardium showed a significant increase in the total amount of non esterified fatty acids (NEFA) in both untreated and mepacrine treated hypoxic hearts compared to normoxic controls, but to a significantly lower level in the mepacrine treated hearts. However, contribution of polyunsaturated NEFAs to total NEFAs did not differ between the groups. Also, neither total amount of fatty acids nor amount of polyunsaturated fatty acids obtained from the 2-position of the phospholipid fraction differed between the treated and untreated groups. In an enzyme assay, mepacrine 1 microM did not inhibit phospholipase A2 activity. We conclude that in our model mepacrine protects the heart from hypoxic injury, but probably by another mechanism than inhibition of phospholipase A2 induced membrane damage.

Animals↗
PubMed1997

Preischemic bradykinin and ischaemic preconditioning in functional recovery of the globally ischaemic rat heart.

OBJECTIVES: Substantial release of bradykinin has been demonstrated to occur during short periods of myocardial ischaemia in various species. The aim of the present study was to investigate the protective effect of bradykinin in ischaemia and whether bradykinin could be involved in ischaemic preconditioning in the rat heart. METHODS: Isolated, buffer-perfused hearts were subjected to 30 min of global ischaemia, followed by 30 min of reperfusion. Postischaemic functional recovery was recorded in the following groups: (1) control; (2) treatment with 0.1 microM bradykinin for 10 min before ischaemia (BK); (3) bradykinin treatment combined with pretreatment with the specific bradykinin B2-receptor antagonist, HOE 140; (4) ischaemic preconditioning by 5 min ischaemia +5 min reperfusion prior to sustained ischaemia (i.p.); and (5) ischaemic preconditioning combined with HOE 140 administration. RESULTS: Postischaemic myocardial function was significantly improved in both BK and i.p. groups (developed pressure 66.9 +/- 6.8 and 67.6 +/- 7.1 mmHg, respectively, vs. 43.1 +/- 5.9 mmHg in controls, P < 0.05). Pretreatment with 1 microM HOE 140 completely abolished the effect of bradykinin, while protection achieved by i.p. was unaltered by this drug. None of the protective interventions was associated with any significant improvement in myocardial adenosine triphosphate, creatine phosphate, glycogen, lactate or glucose tissue levels, detected either at the end of ischaemia or after 30 min of reperfusion. CONCLUSIONS: Bradykinin, acting via B2-receptors, can protect against postischaemic contractile dysfunction to a similar extent as i.p.. An involvement of B2-receptors in the ischaemic preconditioning phenomenon could, however, not be demonstrated.

Adenosine Triphosphate↗