How to discriminate between hibernating and stunned myocardium.

AIM: The aim of the present study was to examine if it is possible to discriminate between hibernating and stunned myocardium in vivo by determining the ratio between diastolic and systolic coronary arterial inflow and by measuring oxygen saturation in draining coronary venous blood. METHODS: Experiments were performed in 32 open chest pigs anesthetized with sodium pentobarbital. In 11 pigs hibernation was induced in a part of the left ventricular myocardium by reducing flow in the mid-left anterior descending coronary artery (LAD) to about 60% of baseline flow. In 12 pigs stunning was induced by occluding mid-LAD twice for 10 min with a 30 min interval. In 9 pigs (control group) coronary flow was not manipulated. RESULTS: We found, at comparable degrees of regional dysfunction, that the ratio between diastolic and systolic flow in stunned myocardium remained unaltered, but fell from about 2 to 1 in hibernating myocardium. Furthermore, coronary venous oxygen saturation decreased from about 30% to 17% in blood draining hibernating myocardium, but remained statistically unaltered in blood draining stunned myocardium. CONCLUSION: We conclude that it is possible to discriminate between hibernating and stunned myocardium by measuring phasic coronary arterial blood flow and oxygen saturation in blood draining the region in question. During hibernation only, the diastolic flow component of coronary arterial inflow is reduced and the coronary venous oxygen extraction increased.

Cardiac fibrinolytic capacity is markedly increased after brief periods of local myocardial ischemia, but declines following successive periods in anesthetized pigs.

BACKGROUND: Fibrinolysis in blood is mainly reflected by the activities of tissue plasminogen activator (tPA) and of plasminogen activator inhibitor-1 (PAI-1). The effect of myocardial ischemia on their activities in the coronary circulation is, however, not established. OBJECTIVES: With an improved experimental model, we therefore examined the effect of a brief period of myocardial ischemia on their activities. Furthermore, the consequences of repeated periods of ischemia, mimicking the situations in patients with unstable angina, were investigated. METHODS: In six anesthetized pigs, we occluded the distal left anterior descending coronary artery (LAD) four times for 10 min with 40 min intervals and determined the activities of tPA and PAI-1 in arterial and coronary venous blood. By simultaneously recording LAD flow, we could estimate cardiac release of these factors at baseline conditions and during reperfusion. RESULTS: Neither net cardiac release of PAI-1 nor alterations in plasma PAI-1 levels were demonstrated during the experiment. However, a significant net release of tPA activity of 10.4 +/- 3.2 IU mL(-1) (P < 0.005) was recorded during baseline conditions. During reperfusion following the first period of ischemia, the cardiac release of tPA activity increased to a peak of 103 +/- 30-fold baseline release, but declined progressively after repeated periods of ischemia. After the fourth period, tPA release did not exceed an estimated baseline accumulation during ischemia and early reperfusion. CONCLUSIONS: In this porcine model, a substantial local increase in fibrinolytic capacity was observed after brief periods of ischemia, but declined subsequently by repeated periods of ischemia.

Pentobarbital versus medetomidine-ketamine-fentanyl anaesthesia: effects on haemodynamics and the incidence of ischaemia-induced ventricular fibrillation in swine.

The present study was performed to compare haemodynamic variables at baseline and the incidence of ventricular fibrillation during the early phase of ischaemia in swine during pentobarbital or medetomidine-ketamine-fentanyl anaesthesia. Twenty-two swine (mean +/- SD: 29+/- 3 kg) were anaesthetized with sodium pentobarbital (induction with 36 mg/kg intraperitoneally, and maintenance with 5-20 mg/kg/h intravenously [i.v.]) and 6 swine (27+/- 3 kg) were anaesthetized with ketamine and fentanyl (premedicated with medetomidine 0.1 mg/kg and ketamine 10 mg/kg intramuscularly, induction with ketamine 20 mg/kg and fentanyl 0.025 mg/kg i.v., and maintenance with ketamine 20 mg/kg/h and fentanyl 0.025 mg/kg/h i.v.). After a stabilization period of 30 min, the left anterior descending coronary artery (LAD) was occluded for 10 min. Haemodynamic data and occurrence of ventricular fibrillation were recorded. The ischaemic area was measured by fluorescing microspheres. Swine anaesthetized with medetomidine-ketamine-fentanyl had significantly lower heart rate, myocardial contractility, peak left ventricular pressure, arterial blood pressure, aortic blood flow, myocardial blood flow and cardiac index at baseline, than swine anaesthetized with pentobarbital. Whereas none of the swine anaesthetized with pentobarbital fibrillated during the LAD occlusion, ventricular fibrillation occurred in 83% of the animals anaesthetized with medetomidine-ketamine-fentanyl (P< 0.001). No significant difference was found in size of ischaemic area between the two groups. Thus, we show a depression in haemodynamic variables at baseline and a higher incidence of ventricular fibrillation during the early phase of ischaemia in swine anaesthetized with medetomidine-ketamine-fentanyl compared to swine anaesthetized with pentobarbital.

Myocardial extracellular signal regulatory kinases are activated by laser treatment.

AIM: Transmyocardial laser revascularization (TMR) and percutaneous transluminal myocardial laser revascularization (PTMR) have anti-anginal effects on certain groups of patients with ischemic heart disease, possibly by inducing myocardial neoangiogenesis through the mechanical injury. Here we examine the effects of TMR and PTMR on extracellular signal regulatory kinases (ERKs), which have been implicated in the control of neoangiogenesis in vitro. METHODS: Eight pigs were anesthetized with ketamine and fentanyl. In five pigs TMR was performed in the left ventricular anterior wall and PTMR in the posterior wall. Biopsies were taken either after 2 hours, 3, 7, 14, and 30 days. Three pigs served as controls and provided samples for baseline values and time-matched controls at 2 hours and 3 days. ERKs activity was determined by increased phosphorylation of myelin basic protein. Total ERKs protein abundance was determined by Western blot with an antibody against ERK1 and ERK2. RESULTS: It was found that ERKs activity was higher in all samples from the laser treated myocardium than in the control sample at baseline (TMR: >or=1878 pmol Pi x min(-1) mg pr(-1) vs 104 pmol Pi x min(-1) mg pr(-1), respectively, p<0.05. PTMR: >or=346 pmol Pi x min(-1) mg pr(-1) vs 136 pmol Pi min(-1) mg pr(-1), respectively, p<0.05). The time-matched samples showed increased activities of ERKs after laser treatment. The protein level of ERKs in myocardium treated with TMR and PTMR parallelled the data on ERKs activity. CONCLUSIONS: Our data suggest that the ERKs system is activated in the porcine heart by the mechanical injury of TMR and PTMR.

Reduced calcium tolerance in rat cardiomyocytes after myocardial infarction.

During ischaemia and reperfusion the intracellular Na+ concentration is elevated in the cardiomyocytes and the cells are depolarized, both favouring reverse mode Na,Ca-exchange loading of the cell with Ca2+. We examined whether cardiomyocytes from rats with congestive heart failure (CHF) and younger rats (HINCX) which both have a high expression of the Na,Ca-exchanger protein (NCX) showed reduced tolerance to extracellular Ca2+. The CHF was induced in Isofluran anaesthetized rats by left coronary artery ligation. Isolated cardiomyocytes were loaded with Fura-2AM and 140 mm Na+ and exposed to 0.05 mm Ca2+. Expression of the Na,Ca-exchanger protein was analysed. Fura-2 340/380 ratio rose more rapidly in HINCX and CHF than in SHAM, and the rise was abolished by Ni2+. Hypercontracture developed more frequently in HINCX and CHF than in SHAM cells. The amount of NCX was 54% higher in HINCX and 76% higher in CHF compared with SHAM. Na+-loaded cardiomyocytes from CHF and HINCX rats are more susceptible to Ca2+ overload than SHAM cells because of the increased capacity for Na,Ca-exchange.

Myocardial laser revascularization in the year 2000 as seen by a Norwegian specialist panel. The process of evaluating and implementing new methods in clinical practice.

OBJECTIVE: In Norway "Transmyocardial laser revascularization" as a routine method was prohibited by the Ministry of Health in 1995 due to lacking evidence of treatment effect and concerns about procedural morbidity and mortality. In 1999 Norwegian health authorities asked for a re-evaluation of the method based on a systematic review of literature. METHODS: Medline and Embase were searched and a total of 267 articles were identified. Publications were classified by an expert panel according to type of study and importance for the project. RESULTS: Based on the literature review the panel concluded that heart laser treatment does not have a life-saving effect, nor does it improve myocardial function. However, the method has a considerable short-term symptomatic effect, the mechanism of which is not understood. Neoangiogenesis, denervation and placebo may play a role. Based on the report the Norwegian health authorities recommended use of this method be restricted to scientific trials only. CONCLUSIONS: Based on a systematic literature review it was concluded that the only documented effect of heart laser treatment is symptom relief, the mechanism for which is unclear. It could partly or totally be a placebo effect. A conflict of interest may arise when new technologies are to be implemented in health care. The communication between professionals evaluating scientific results and decision makers is challenging. Quality assurance of this process may be obtained by use of expert panels working under the auspices of an official institution.

Echocardiographic criteria for detection of postinfarction congestive heart failure in rats.

We evaluated postinfarction myocardial function in rats and determined echocardiographic criteria for congestive heart failure (CHF) using high performance echocardiography. Extensive myocardial infarction (MI) was induced in rats by left coronary occlusion. Sham-operated animals served as controls. Five weeks later, high-frame rate ( approximately 200 Hz), fully digitized, shallow-focus (10-25 mm), two-dimensional, M-mode and Doppler echocardiography was performed. A J-tree cluster analysis was performed using parameters indicative of CHF. Reproducibility was examined. The cluster analysis joined the animals into one Sham and two MI clusters. One of the MI clusters had clinical characteristics of CHF and elevated left ventricular end diastolic pressure. Among the echocardiographic variables, only posterior wall shortening velocity separated the failing and nonfailing MI clusters. We conclude that, by high frame rate echocardiography, it is possible to obtain high- quality recordings in rats. It is feasible to distinguish MI rats with CHF due to myocardial dysfunction from those without failure and to perform longitudinal studies on myocardial function.

Effects on infarct size and on arrhythmias by controlling reflow after myocardial ischaemia in pigs.

Part of the myocardial damage after an ischaemic period might be related to the reperfusion conditions. Many abrupt changes occurring in the heart during reperfusion may add to the damage during the preceding ischaemic period, and increase in infarct size. In this study we tested the hypothesis that infarct size and occurrence of ventricular arrhythmias might be reduced by restricting reflow after an ischaemic period. Seventeen pigs underwent 45 min of total occlusion of the left anterior descending coronary artery with an hydraulic occluder. In the intervention group reperfusion was restricted to 50% of baseline during the first minute, to 100% during the next minute, kept constant for 1 min, and thereafter allowed to increase by 50% of baseline flow every minute until free reflow. In the control group reflow was not restricted. Arrhythmias were recorded. After 2.5 h of reperfusion the heart was excised. Infarct size was measured by using triphenyltetrazolium chloride (delineation of necrosis), fluorescent microspheres (delineation of area at risk) and planimetry. No reduction in infarct size (% of area at risk) was found between the intervention group and the control group (75.9 +/- 5.3% vs. 72.4 +/- 4.3%). The incidence of ventricular arrhythmias and ventricular fibrillation were not found to be different between the groups during reperfusion. Hemodynamic parameters were not significantly different between the two groups. Our data indicate that no substantial protection against myocardial infarct or ventricular arrhythmias could be achieved by controlling reflow using the present protocol after a period of myocardial ischaemia in pigs. Accordingly, our data do not support the notion that control of reflow may be beneficial when treating coronary artery occlusion with percutaneous coronary angioplasty (PCA).

Endotoxemia alters splanchnic capacitance.

The splanchnic circulation constitutes a major portion of the total capacitance vasculature and may affect venous return and subsequently cardiac output during low output states. This study assessed the effects of rapid (10 microg/kg over 5 min) and slow (10 microg/kg over 60 min) induction of endotoxin (Escherichia coli) shock on splanchnic blood volume in 8 farm swine. Blood volume was measured by using Tc99m-labeled erythrocytes and radionuclide imaging. Baseline arterial pressure (MAP), central venous pressure (CVP), and liver, splenic, mesenteric and total splanchnic volumes were stable during the 30-min baseline. Approximately 30 min after the rapid endotoxin infusion, splenic volume decreased by 45%, whereas liver volume increased by 40% and MAP decreased by 60% (P < 0.01). The reduction in splenic volume occurred within 10 min of the endotoxin infusion, whereas liver volume changes occurred after MAP reduction. The slow endotoxin infusion also reduced splenic volume by approximately 50% (P = 0.05), whereas MAP declined by 30% (P < 0.05). However, the slow endotoxin infusion lowered liver volume (P < 0.05). Mesenteric volume was unaffected by the fast or slow endotoxin infusion. Total splanchnic volume was unaffected by the fast infusion but decreased by 37% in the slow infusion group (P < 0.05). In summary, E. coli endotoxin reduces splenic blood volume and increases liver blood volume after acute hypotension ensues. Endotoxin does not increase total splanchnic blood volume and may actually decrease total splanchnic volume in the absence of circulatory collapse. This endotoxin shock model is not associated with blood volume pooling in the splanchnic capacitance circulation.

Transmyocardial laser treatment reduces ischemia-induced ventricular fibrillation during the early phase (1a) after coronary artery occlusion in open chest anesthetized pigs.

INTRODUCTION: It has previously been shown that transmyocardial revascularization with laser (TMR) prior to coronary artery occlusion decreases the occurrence of ischemia-induced arrhythmias. The aim of the present study was to determine the effects of TMR on ventricular fibrillation and other arrhythmias during the early (1a) and late phase (1b) of ischemia in pigs. METHODS: In six pigs TMR was performed in the anterior wall of the left ventricle 60 minutes prior to occlusion of the proximal LAD. Six other pigs were subjected to coronary occlusion without preceding TMR and served as controls. RESULTS: During the 30 min period with LAD occlusion ventricular fibrillation occurred 22 times in 5 of 6 control animals (20 episodes in phase la, 2 in phase 1b), whereas none of the animals subjected to TMR prior to the coronary artery occlusion developed ventricular fibrillation (p<0.01). The total number of premature beats per animal was lower during the early phase (la) after LAD occlusion in the TMR group than in the control group (18+/-13 vs 248+/-82, p<0.05). CONCLUSIONS: TMR prior to occlusion of LAD reduced the occurrence of early phase (la) ischemia-induced ventricular fibrillation and premature beats. This anti-fibrillatory effect might explain the improved survival observed in experimental studies after TMR prior to coronary artery occlusion found by others.

Importance of heart rate for acute hibernation in isolated blood-perfused piglet hearts.

BACKGROUND: Hibernating myocardium may benefit from revascularization. There are several experimental models for acute hibernation. In intact hearts low-flow ischemia causes time-dependent metabolic alterations, termed "metabolic adaptation". In isolated heart preparations metabolic responses to low-flow ischemia vary, and signs of metabolic adaptation are not consistently found. In isolated hearts global ischemia may cause bradycardia unless the hearts are paced. We hypothesized that the lack of consistent metabolic adaptation to low-flow ischemia in isolated hearts might be due to bradycardia during ischemia. In this study we investigated the influence of heart rate on metabolism and function in an isolated heart preparation. METHODS: Isolated blood-perfused piglet hearts were subjected to 120 min 10% flow. In groups A (n=9) and B (n=4) hearts were not paced during ischemia, in groups C (n=5) and D (n=5) hearts were paced at pre-ischemic heart rate during ischemia. RESULTS: Without pacing, heart rate declined to approximately 1/3 during ischemia and anaerobic metabolism showed a slight decline over time. With pacing, production of protons, pCO2 and lactate showed a bell-shaped curve which peaked at 20-25 min of ischemia, followed by a subsequent decline towards the end of ischemia (overall p < 0.001 for all). However, reperfusion revealed impaired recovery of function in paced hearts compared to non-paced hearts (53 +/- 7% vs 77 +/- 4%, p < 0.05) concomitant with higher release of creatine kinase (455 +/- 93 IU/100 g vs 106 +/- 13 IU/100 g, p < 0.01). CONCLUSIONS: When heart rate is allowed to decline during low-flow ischemia in isolated piglet hearts, signs of metabolic adaptation are not evident. When hearts are paced during ischemia time-dependent alterations in anaerobic metabolism occur, resembling observations seen in intact beating hearts. However, paced hearts also show indications of increased cellular injury, indicating that in paced hearts the metabolic consequences are mostly due to increased irreversible cell injury. Thus, the model for acute hibernation with 10% flow in isolated blood-perfused piglet hearts are critically dependent on bradycardia during ischemia.

Elevated levels of endogenous adenosine alter metabolism and enhance reduction in contractile function during low-flow ischemia: associated changes in expression of Ca(2+)-ATPase and phospholamban.

Adenosine has several potentially cardioprotective effects including vasodilatation, reduction in heart rate and alterations in metabolism. Adenosine inhibits catecholamine-induced increase in contractile function mainly through inhibition of phosphorylation of phospholamban (PLB), the main regulatory protein of Ca(2+)-ATPase in sarcoplasmic reticulum (SR), and during ischemia it reduces calcium (Ca2+) overload. In this study we examined the effects of endogenous adenosine on contractile function and metabolism during low-flow ischemia (LFI) and investigated whether endogenous adenosine can alter expression of the Ca(2+)-ATPase/PLB-system and other Ca(2+)-regulatory proteins. Isolated blood-perfused piglet hearts underwent 120 min 10% flow. Hearts were treated with either saline, the adenosine receptor blocker (8)-sulfophenyl theophylline (8SPT, 300 micromol/l) or the nucleoside transport inhibitor draflazine (1 micromol/l). During LFI, 8SPT did not substantially influence metabolic or functional responses. However, draflazine enhanced the reduction in heart rate, contractile force and MVO(2), with less release of H+ and CO2. Before LFI there were no significant differences between groups for any of the proteins (Ca(2+)-ATPase, ryanodine-receptor, Na+/K(+)-ATPase) or mRNAs (Ca(2+)-ATPase, PLB, calsequestrin, Na+/Ca(2+)-exchanger) measured. At end of LFI mRNA-level of PLB was higher in draflazine-treated hearts compared to both other groups (P<0.01 vs both). Also, at end of LFI protein-level of Ca(2+)-ATPase was lower in draflazine-treated hearts (P<0.05 vs both), and a parallel trend towards a lower mRNA-level was seen (P=0.11 vs saline and P=0.43 vs 8SPT). During LFI tissue Ca2+ tended to rise in saline- and 8SPT-treated hearts but not in draflazine-treated hearts (at end of LFI, P=0.01 vs 8SPT). We conclude that the amount of adenosine normally produced during LFI does not substantially influence function and metabolism. However, increased endogenous levels by draflazine enhance downregulation of function and reduce signs of anaerobic metabolism. At end of LFI associated changes in expression of PLB and Ca(2+)-ATPase were seen. The functional significance was not determined in the present study. However, altered protein-levels might influence Ca(2+)-handling in sarcoplasmic reticulum and thus affect contractile force and tolerance to ischemia.

Transventricular non-transmural laser treatment of hypoperfused porcine myocardium acutely reduces left ventricular contractile function.

OBJECTIVE: Creation of non-transmural myocardial channels by lasers transmitted through endovascular fiberoptics is a novel therapeutic option in the management of patients with coronary artery disease. The acute effect of transventricular laser treatment (TvL) on coronary blood flow, myocardial metabolism and left ventricular function are not well established. METHODS: In five anesthetized pigs, flow in the proximal left anterior descending coronary artery (LAD) was reduced and maintained at 70% of baseline. A venous shunt had previously been established draining the hypoperfused region. At 30 min of ischemia, non-transmural myocardial channels were created through the endocardium using a Ho:YAG laser. We measured (a) left ventricular, central venous and arterial pressures, (b) ascending aortic, LAD and coronary venous blood flows, as well as (c) lactate concentration and blood gases in arterial and coronary venous blood, prior to ischemia (baseline), before and 30 min after TvL. Data (given as mean +/- SD) were analyzed with repeated measures ANOVA. RESULTS: Reduction of LAD blood flow resulted in reduced regional coronary venous blood flow and myocardial oxygen consumption, conversion of regional myocardial lactate uptake to release and adaptation of left ventricular contractility to a lower level. Following transventricular laser, the peak left ventricular systolic pressure declined from 86 +/- 12 to 77 +/- 11 mmHg (P < 0.05), its maximal first positive derivative (LV dP/dt) declined from 900 +/- 221 to 763 +/- 127 mmHg/s (P < 0.05) and the stroke volume decreased from 19.2 +/- 4.1 to 16.4 +/- 5.4 ml (P < 0.05). The changes in regional coronary venous flow, myocardial oxygen consumption and myocardial lactate release after TvL were not significant compared to before TvL. Significant intramural hematomas and tissue destruction were found around the channels at autopsy and by histologic examination. CONCLUSION: Transventricular laser treatment of hypoperfused myocardium decreased left ventricular contractility in the acute phase, possibly due to development of perichannel hematomas and disruption of the wall architecture. In addition, TvL did not alter the regional myocardial oxygen supply/demand balance. These results call for caution in the treatment of patients with coronary artery disease by transventricular Ho-YAG laser when there is significant impairment of the left ventricular contractile function.

Microembolization in pigs: effects on coronary blood flow and myocardial ischemic tolerance.

Coronary microembolization has been reported to increase coronary blood flow (CBF) through adenosine release. Because adenosine may increase ischemic tolerance against infarction, we tested the hypothesis that myocardial microembolization, a common finding in patients with ischemic heart disease, induces cardioprotection. Additionally, because the use of microspheres is a common tool to measure tissue perfusion, the effects of small amounts of microspheres on CBF were examined. Using anesthetized pigs, we measured CBF with a transit time flow probe on the left anterior descending coronary artery (LAD). In six pigs the relationship between the amount of injected microspheres (0-40 x 10(6), 15 micrometer in diameter, left atrial injections) and the effect on CBF was examined. Coronary hyperemia occurred, which was linearly related to the amount of microspheres injected: maximal increase in CBF (%) = 2.8 +/- 1.5 (SE) + (5.8 +/- 0.7 x 10(-7) x number of injected microspheres). Because injection of 40 x 10(6) microspheres induced a long-lasting hyperemic response, which could be blocked by 8-p-sulfophenyl theophylline, ischemic tolerance was examined in five other pigs after two injections, each of 40 x 10(6) microspheres, at a 30-min interval. Six control pigs had no injections. Ischemic tolerance was evaluated by measuring infarct size (tetrazolium stain) as the percentage of area at risk (fluorescent particles) after 45 min of LAD occlusion followed by 2 h of reperfusion. Pretreatment by microspheres increased infarct size from 60 +/- 3% of area at risk in control animals to 84 +/- 6% (P < 0.05). The injection of microspheres induced a significant hyperemic flow response without causing necrosis by itself. We conclude that microembolization, evoking coronary hyperemia, does not improve but reduces myocardial ischemic tolerance against infarction in pigs.

Transmyocardial laser induces coronary hyperemia and reduces ischemia-related arrhythmias, but fails to delay development of myocardial necrosis after coronary artery occlusion in pigs.

BACKGROUND: Several investigators have reported that transmyocardial revascularization (TMR) prior to acute coronary artery occlusion improves regional myocardial function and reduces the infarct size in animals with significant coronary collateral circulation. Whether the protective effect of TMR is due to perfusion through the laser-made channels, increased collateral flow or other mechanisms remains unresolved. The aim of this study was to investigate whether TMR performed prior to acute coronary artery occlusion could offer protection from ischemic injury in the pig, an animal with limited native collateral coronary circulation. METHODS: In one group (n=4), TMR was performed in the anterior wall of the left ventricle 30 minutes prior to occlusion of the proximal LAD for 45 minutes. The other group (n=6) was subjected to transient ischemia of the same duration without previous TMR. Area at risk and infarct size were determined after sacrifice. RESULTS: No significant difference was found in the infarct size between the two groups (69+/-2% in the TMR group versus 62+/-4% in the control group). However, the arrhythmic index during the period of ischemia was significantly lower in the TMR group (1.0+/-0.3 vs 8.3+/-2.2, p<0.001). Blood flow in LAD increased to a maximum of 135+/-6% of baseline level three minutes after the end of the TMR procedure. CONCLUSIONS: TMR failed to reduce the infarct size following acute coronary artery occlusion in the pig, an animal with a small collateral coronary flow capacity, but reduced ischemia-related arrhythmias and increased coronary flow transiently.

Duration of ischaemic preconditioning and importance of size of area at risk in pigs.

An explanation of the preconditioning phenomenon must account for the biology of the phenomenon. Here we provide a more thorough characterization of ischaemic preconditioning (IPC), examining temporal characteristics and the importance of the size of area at risk. IPC was induced by two 10-min LAD occlusions separated by 30 min reperfusion in pentobarbital anaesthetized open-chest pigs. The last brief occlusion was followed by either 30 min, 2 h or 4 h of reperfusion. The degree of protection was evaluated by measuring infarct size after either 45 or 60 min LAD occlusion followed by 2 h of reperfusion. To examine the importance of the size of area at risk, the occlusion site on LAD was varied between pigs. IPC followed by 30 min and 2 h of reperfusion reduced infarct size from 58+/-2% of area at risk to 15+/-4% (P<0.05) and 15+/-6% (P<0.05), respectively, by 45 min of LAD occlusion. After 4 h of reperfusion the infarct size-limiting effect of IPC was still prominent when a test ischaemic period of 45 min was used (47+/-5%vs 13+/-1%P<0.05). IPC was paralleled by an increased incidence of ventricular fibrillation during the early phase of the prolonged LAD occlusion after 30 min, 2 h and 4 h of reperfusion. Although no correlation was found between infarct size (as a percentage of area at risk) and area at risk (as a percentage of ventricular weight) in control pigs, a positive correlation was found between these variables in preconditioned pigs. We conclude that the infarct size-limiting effect of IPC lasts at least 4 h and that it is paralleled by profibrillatory effects in open-chest pigs. Furthermore, the infarct size-limiting effect of IPC depends on the size of area at risk, being most pronounced when area at risk is small.

Cardiac accumulation of citrate during brief myocardial ischaemia and reperfusion in the pig in vivo.

Citrate is a key intermediate in energy metabolism and an inhibitor of phosphofructokinase of the glycolytic pathway. During myocardial ischaemia glycolysis is the main source of cardiac ATP. The aim of the present study was to determine if myocardial ischaemia and reperfusion alter cardiac tissue levels of citrate. Open-chest, anaesthetized pigs were subjected to 10 min of regional myocardial ischaemia by occlusion of the left anterior descending coronary artery, with and without reperfusion, and to 10 min of global ischaemia by circulatory arrest. Citrate, amino acids, glucose and NH3 were measured in biopsies. Ischaemia, whether regional or global, caused a 60-70% increase in tissue levels of citrate. During 1 min of reperfusion following regional ischaemia the level of citrate increased 460%, to approximately 600 nmol g-1 wet weight. The level of glutamate decreased by 20-33% (corresponding to 1300-2200 nmol g-1 wet weight), indicating net consumption of this amino acid during ischaemia. The level of aspartate decreased 50% indicating conversion of aspartate to oxaloacetate for the synthesis of citrate. Theoretically, the accumulation of myocardial citrate during brief ischaemia and early reperfusion is large enough to significantly inhibit phosphofructokinase activity and could therefore affect the ability of the myocardium to increase the glycolytic rate in response to ischaemia. This could, however, be partly compensated by the metabolism of myocardial glutamate.

A new approach to normalize myocardial temperature in the open-chest pig model.

To prevent unphysiological temperature fluctuations in the myocardium in the open-chest model, we constructed a thermocage. Five pigs under pentobarbital sodium anesthesia underwent repetitive left anterior descending (LAD) coronary artery occlusions. Myocardial temperature was measured without any thoracic temperature-controlling device and in the presence of either a heating lamp or the thermocage. Without any thoracic temperature-controlling device, the temperature at 5-mm myocardial depth was 1.28 +/- 0.33 degrees C below the intra-abdominal temperature (P < 0.05). During a proximal 5-min LAD occlusion, myocardial temperature decreased by 1.86 +/- 1.02 degrees C in the ischemic area (P < 0.05). Both the heating lamp and the thermocage abolished the difference between intra-abdominal and myocardial temperatures and prevented the decrease in myocardial temperature during ischemia. Only the thermocage minimized myocardial temperature fluctuations due to air currents and prevented epicardial exsiccation. We conclude that either a thermocage or a heating lamp may be used to normalize myocardial temperature in the open-chest pig model. However, the thermocage is superior to the lamp in minimizing temperature fluctuations and preventing epicardial exsiccation.

Effect of different compression--decompression cycles on haemodynamics during ACD-CPR in pigs.

The haemodynamic effects of variations in the relative duration of the compression and active decompression (4 cm/2 cm) during active compression-decompression cardiopulmonary resuscitation (ACD-CPR), 30/70, 50/50 and 70/30, were tested in a randomized cross-over design during ventricular fibrillation in seven anaesthetized pigs (17-23 kg) using an automatic hydraulic chest compression-decompression device. Duty cycles of 50/50 and 70/30 gave significantly higher values than 30/70 for mean carotid blood flow (32 and 36 vs. 21 ml min-1, transit time flow probe, cerebral blood flow (30 and 34 vs. 19, radionuclide microspheres), mean aortic pressure (35 and 41 vs. 29 mmHg) and mean right atrial pressure (24 and 33 vs. 16 mmHg). A higher mean aortic, mean right atrial and mean left ventricular pressure for 70/30 were the only significant differences between 50/50 and 70/30. There were no differences in myocardial blood flow (radionuclide microspheres) or coronary perfusion pressure (CPP, aortic-right atrial pressure) between the three different duty cycles. CPP was positive in both the early and late compression period and during the whole decompression period. The expired CO2 was significantly higher with 70/30 than 30/70 during the compression phase of ACD-CPR. Beyond that no significant differences in the expired CO2 levels were observed. In conclusion a reduction of the compression period to 30% during ACD-CPR reduced the cerebral circulation, the mean aortic and right atrial pressures with no effect on the myocardial blood flow of varying the compression-decompression cycle.

[Transient postischemic myocardial injury--a condition of practical clinical significance?]. / Forbigående postiskemisk myokardskade--har tilstanden praktisk klinisk betydning?

After a brief ischemic period, a prolonged phase of cardiac dysfunction develops. This transient dysfunction is now known as myocardial stunning. In this article we list the pathophysiological conditions in which myocardial stunning is most likely to occur in humans, and we discuss how it can be diagnosed. Although stunning is a reversible condition, its clinical implications can be life threatening. However, knowledge of the mechanisms involved may help improve the treatment of patients with myocardial stunning where this occurs after revascularization procedures for instance, and after cardiac arrest.