Intermittent Myocardial Ischemia Research Articles

Functional and proteomic investigation of potential role of steroid hormones in regulating early cardiac recovery in a rat model of isoproterenol induced intermittent myocardial ischemia

Abstract Introduction Women benefit from higher levels of protection from cardiovascular diseases until menopause, after which they gradually lose their privileged status. Pivotal role of sex hormones, primarily estrogens were the focus of interest in explaining this clinical observation. Estradiol (E2) was a prime target of these investigations showing promising results. Nonetheless the potential influence of other estrogens and numerous estrogen metabolites have so far been neglected. Purpose The aim of our study was to investigate the influence of circulating steroid hormones on early functional and proteomic changes following repeated ischemic periods in female rats by applying the highly unbiased methods of in vivo pressure-volume analysis and mass spectrometry based proteomics. Methods Diffuse subendocardial ischemia was induced in female (F-Isch) Wistar rats with sc. injection of isoproterenol (ISO, 85mg/kg) daily for two consecutive days, while the control group (F-Co) received an equivalent volume of sc. saline solution. 48 hours after the first injection pressure-volume analysis (P-V) was carried out to assess left ventricular function. FFPE tissue slides were scanned and analyzed digitally, while peptides from the snap frozen left ventricular myocardium were measured by liquid chromatography-tandem mass spectrometry using isobaric labeling (TMT11plex). Serum and plasma samples were taken to measure circulating steroid hormone levels with mass spectrometry. Results Two day induction of ischemia resulted in 17% mortality in F-Isch. ISO treatment resulted in significant myocardial tissue damage compared to controls as assessed by histology. Ischemia led to a prominent impairment of diastolic aspects (active relaxation and myocardial stiffness) of left ventricular function (Tau: 11.1±0.7 vs. 16.1±1.1 F-Co vs. F-Isch; EDPVR: 0.05±0.005 vs. 0.131±0.016 F-Co vs. F-Isch.). Unsupervised hierarchical clustering performed on P-V parameters identified two distinct subgroups of F-Isch with severe or mild functional impairment. Supervised PLS-DA analysis of P-V and hormone datasets found three estrogens that might play a role in determining functional outcomes (2-Hydroxyestrone: 2-OHE1, 4-Hydroxyestrone: 4-OHE1, 4-Methoxyestrone: 4-MeE2). PLS analysis followed by gene ontology enrichment associated E2 and 2-OHE1 concentrations with mitochondrial protein expressions, while 4-OHE1 seemed to influence the reassembly of contractile structures after ischemia. Conclusions Our study has highlighted 2-OHE1 and 4-OHE1 as well as E2 as potentially influential estrogens on early post-ischemic recovery both on functional and on proteomic level. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): New National Excellence Program of the Ministry of Human Capacities of Hungary (ÚNKP-20-3-I-SE-1 to BA. B.) National Research, Development and Innovation Office (NKFIH) of Hungary (K134939 to T. R.)

The direct aortic cannulation for acute type A aortic dissection.

This article describes the surgical techniques demonstrated in our video, “The Direct Aortic Cannulation for Acute type A Aortic Dissection”. Acute type A aortic dissection is a life-threatening condition requiring emergency operation. The choice of arterial cannulation sites to institute cardiopulmonary bypass is still a topic of controversy. Central cannulation directly through the ascending aorta has been reported (1,2). It has a theoretical advantage of not changing the natural antegrade blood flow, and in doing so avoiding intraoperative malperfusion. We believe that accurate positioning of the tip of an arterial cannula is best achieved with epiaortic echo guidance. We use the Seldinger method through the non-dissected part of the aortic wall in most cases, usually via the left side of the ascending aorta. In the current video presentation (Video 1), only the small posterior aspect was not dissected. The case was also complicated by intermittent myocardial ischemia, bicuspid aortic valve and significantly dilated ascending aorta. Video 1 The direct aortic cannulation for acute type A aortic dissection. Here we describe in detail our surgical technique for direct aortic cannulation by the Seldinger method with epiaortic guidance.

Effect and Mechanism of Intermittent Myocardial Ischemia Induced by Exercise on Coronary Collateral Formation

To hypothesize that appropriate intermittent myocardial ischemia induced by exercise could safely promote coronary collateral formation in the ischemic area through the increased expression of vascular endothelial growth factor (VEGF) and its receptor fetal liver kinase-1 (Flk-1). A balloon constrictor was surgically implanted in the first obtuse marginal coronary artery (OM1) of Guangxi BA-MA miniature pigs. The subjects were divided into three groups: sham-operated (SO), pure ischemia (PI), and exercise training (ET). Subjects in the ET group performed individualized treadmill programs with two episodes of exercise-induced ischemia for 8 wks; two preexercise episodes of pure ischemia induced by brief OM1 occlusion were also conducted. Only pure ischemia was induced in the PI group, and the SO group remained sedentary for the experimental period. VEGF and Flk-1 expression levels were measured by Western blot and real-time reverse transcription polymerase chain reaction analyses; capillary density by immunohistochemistry; relative myocardial blood flow by microspheres; and cardiac troponin I by enzyme-linked immunosorbent assay. The relative myocardial blood flow, VEGF, Flk-1, and capillary density in the ET group were statistically higher than those in the PI and SO groups. All parameters in the PI group were statistically higher than those in the SO group. There was no myocardial damage in the ET or PI groups by cardiac troponin I. Intermittent myocardial ischemia induced by exercise with optimal stimulation safely promotes coronary collateral formation through increased VEGF and Flk-1 expression in a porcine model.

Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted β-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of KATP channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, α-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance.

Proteomic analysis of left ventricular tissues following intermittent myocardial ischemia during coronary collateralization in rabbits

Background Repeated transient myocardial ischemia may offer favorable effects to coronary perfusion via collateral circulation, although the underlying molecular mechanisms still remain unclear. This study was designed to evaluate the proteomic changes during this process. Methods Rabbits were randomly divided into sham-operated and ischemic groups (5 each) and were subjected to intermittent myocardial ischemia by inflation or deflation of pneumatic occluders for 4 weeks to establish a controlled myocardial ischemic model. Isolated hearts were subjected to histological observation, microspheric detection, capillary counting and proteomic analysis. Results Elevation of ST segment or back to normal in Lead-II electrocardiogram could be induced by occluders without overt histological and cardiac troponin I alterations. Regional coronary collateral blood flow exhibited a remarkable increase following intermittent inflation of occluders in the ischemic group ( P < 0.01). Simultaneously, capillary numbers per unit area were significantly different between groups ( P < 0.01). Twenty-three differentially expressed protein spots were separated by two-dimensional gel electrophoresis and 13 out of them were identified by MALDI-TOF-MS. Conclusion The present study indicates that the differentially expressed proteins involved in proliferation, growth and energy metabolism following intermittent myocardial ischemia without ischemia-reperfusion injury are likely associated with the development of collateralization beneficial to coronary circulation.

The Effect of Xenon Anesthesia on the Size of Experimental Myocardial Infarction

Volatile anesthetics protect the myocardium from ischemia reperfusion damage. Our hypothesis for this study was that xenon reduces the size of myocardial infarction similar in extent to the reduction associated with ischemic preconditioning. Thirty-six pigs weighing 30-35 kg were anesthetized with thiopental and then randomized into four groups: control (myocardial ischemia only), ischemic preconditioning (five 5-min episodes of intermittent myocardial ischemia), xenon preconditioning (three 10-min exposures to xenon 70% followed by myocardial ischemia), and xenon anesthesia (xenon 70%, continued before and after myocardial ischemia). Myocardial ischemia was induced by placing a tourniquet around the left anterior descending coronary artery for 60 min followed by 2 h of reperfusion. Myocardial infarct size and the area at risk for myocardial infarction were measured by Evans Blue and triphenyl tetrazolium chloride staining, respectively. Mean (sd) myocardial infarct size was reduced from 64% +/- 9% of the area at risk in the control group to 19% +/- 12% with ischemic preconditioning (P < 0.001), and to 50% +/- 9% with xenon anesthesia (P < 0.05 versus control, P < 0.001 versus ischemic preconditioning). Myocardial infarct size was not reduced with xenon preconditioning compared with the control group (59% +/- 11%, P = 0.41). Myocardial infarct size was reduced by ischemic preconditioning but less so by xenon anesthesia. Brief, intermittent exposure to xenon before myocardial ischemia did not reduce myocardial infarct size.

Relation between left ventricular midwall function and coronary vasodilator capacity in arterial hypertension.

In systemic hypertension, depressed left ventricular midwall shortening predicts an adverse outcome and is associated with increased left ventricular relative wall thickness, which has been proposed as an independent predictor of cardiovascular risk and reduced coronary reserve. This study was designed to investigate whether depressed midwall shortening is associated with more critical impairment of coronary function and with exercise-induced myocardial ischemia. Sixty untreated hypertensive patients without coronary artery stenosis and 20 normotensive volunteers underwent exercise ECG testing, standard and transesophageal echocardiography to assess the occurrence of exercise-induced myocardial ischemia, left ventricular mass, geometry, and midwall shortening, and coronary vasodilator capacity. Compared with hypertensive patients with normal midwall shortening, those with depressed function (n=15) had higher minimum coronary resistance (1.19+/-0.27 versus 1.39+/-0.20 mm Hg/cm per second, P<0.01) and prevalence of exercise-induced myocardial ischemia (36 versus 67%, P<0.05). Within the hypertensive group, midwall shortening was inversely related to minimum coronary resistance (r=-0.42, P<0.01). Compared with patients with an exercise ECG test negative for myocardial ischemia, those with a positive test result (n=26) had higher minimum coronary resistance (1.13+/-0.21 versus 1.38+/-0.27 mm Hg/cm per second, P<0.01) and lower midwall shortening (104+/-16 versus 93+/-14%, P<0.01). We conclude that hypertensive patients with depressed midwall shortening have more severe impairment of coronary function and a higher prevalence of exercise-induced myocardial ischemia as compared with hypertensive patients with normal midwall shortening. These findings suggest that a decrease in myocardial performance may be related, at least in part, to chronic intermittent myocardial ischemia caused by a critical impairment of coronary vasodilator capacity.

Anaerobic Threshold and Maximal Oxygen Uptake in Patients with Coronary Artery Disease and Stable Angina before and after Percutaneous Transluminal Coronary Angioplasty

In this study, we investigated the effect of percutaneous transluminal coronary angioplasty (PTCA) on functional exercise capacity, oxygen uptake at anaerobic threshold (VO_2AT) and maximal oxygen uptake (VO_2max) in patients with coronary artery disease (CAD). Twenty-five patients with CAD and stable angina pectoris underwent spiroergometry before and after PTCA. All patients had reduced functional capacity with Weber class B in 5, class C in 16 and class D in 4 patients with mean VO_2AT of 9.4 ± 1.5 ml·kg^–1·min^–1 and mean VO_2max of 13.3 ± 3.3 ml· kg^–1·min^–1. After PTCA, VO_2max (15.8 ± 3.1 ml·kg^–1· min^–1) increased significantly (p < 0.001) compared to before PTCA. Subgroup analysis revealed that patients with low functional capacity before PTCA (VO_2max <15 ml· kg^–1· min^–1) had the most benefit from PTCA with an increase in VO_2AT from 8.7 ± 1.0 to 9.6 ± 1.4 ml·kg^–1· min^–1 (p < 0.05) and of VO_2max from 11.3 ± 2.2to 14.8 ± 3.5 ml·kg^–1·min^–1 (p < 0.001) whereas in patients with VO_2max >15 ml·kg^–1·min^–1, VO_2AT (p = 0.9) and VO_2max (p = 0.2) did not improve significantly. In conclusion, there is reduced functional capacity and VO_2max which improved after PTCA in CAD patients. In patients with low VO_2max before PTCA, functional capacity, VO_2AT and VO_2max significantly improved after PTCA, suggesting reversible myocardial impairment induced by intermittent myocardial ischemia. Patients with higher VO_2max had no significant benefit from PTCA with respect to functional capacity, VO_2max and VO_2AT.

Pathophysiologische Grundlagen der instabilen Koronarsyndrome

The acute coronary syndrome is the manifestation of a plaque rupture in a coronary artery, which can lead to intermittent or prolonged regional myocardial ischemia. In such a situation, the underlying atherosclerotic lesion is a complex one. Moreover, the mechanisms leading to the instability of an atherosclerotic plaque are complex themselves. This makes it problematic to systematically analyze the nature of the acute coronary syndrome. Moreover, no animal model is available to study this process. Substantial insights into the basis of the acute coronary syndrome have been gathered by pathomorphological analyses, which have helped to identify a number of criteria describing a vulnerable plaque. Clinical studies have helped to identify the thrombotic component as an important aspect of the clinical manifestation of the acute coronary syndrome. Based on such data, well-defined antithrombotic strategies play an important role in today's therapy of the acute coronary syndrome. Concerning the triggering mechanisms for an acute coronary syndrome, there is a number of suspected processes, the most important of which is local inflammation of the coronary plaque. Inflammatory processes have recently been recognized as important stimulators of vascular modeling during atherogenesis. These inflammatory mechanisms involve a number of different cytokines, cells of the immune system and other components of the immune systems such as the complement cascade. C-reactive protein may even be a link between systemic and local inflammatory processes, because it has been shown to be systemically elevated in patients with unstable angina, and--most recently--has been shown to be involved in the initiation and progression of early atherosclerotic lesions. Local inflammation of the atherosclerotic plaques induces the expression of a number of growth factors and other potent molecules that contribute to vascular remodeling. These substances are acting on smooth muscle cells, fibroblasts as well as on the extracellular matrix and include growth factors, matrixmetalloproteinases and tissue inhibitors of metalloproteinase. Another component of potential significance within the unstable plaque is the process called plaque-angiogenesis. Plaque-angiogenesis occurs within complicated atherosclerotic plaques, the process of angiogenesis leads to destabilization of the extracellular matrix and, moreover, newly formed capillaries are more likely to rupture and may therefore be an important trigger of plaque rupture and of the acute coronary syndrome. A number of molecular strategies including inhibition of matrix metalloproteinasis or inhibitors of angiogenesis may turn out to stabilize the vulnerable plaque. Until these therapeutic concepts may be used in the clinic, our therapeutic repertoire will mostly consist of antithrombotic and entire antiinflammatory approaches.

Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia

Nitroglycerin and the long-acting nitrates are widely used in all of the anginal syndromes and have proven effectiveness in relieving or preventing myocardial ischemia. Recent developments into nitrate mechanisms of action provide new insights as to the many anti-ischemic effects of these agents. Important concepts relating to coronary arterial endothelial function are germane to nitrate therapy. Endothelial-derived relaxing factor (EDRF) is presently believed to be nitric oxide (NO), which exerts vasodilatory and/or antiplatelet actions by increasing intracellular cyclic guanosine monophosphate as a result of activation of the enzyme guanylate cyclase. In the setting of coronary atherosclerosis, or even hyperlipidemia without histologic vascular disease, endothelial dysfunction may be present, promoting a vasoconstrictor/proplatetet aggregatory milieu. Nitroglycerin and the organic nitrates are NO donors; NO is the final product of nitrate metabolism, and in the vascular smooth muscle NO induces relaxation, resulting in vasodilation of arteries and veins. In the presence of inadequate EDRF production and/or release, it appears that nitroglycerin may partially replenish EDRF-like activity. Nitrates have long been known to have major peripheral circulatory actions resulting in a marked decrease in cardiac work. Venodilation and arterial relaxation result in a decrease in intracardiac chamber size and pressures, with a resultant decrease in myocardial oxygen consumption. In addition, a variety of direct coronary circulatory actions of the nitrates have been documented. These include not only epicardial coronary artery dilation, but the prevention of coronary vasoconstriction, enhanced collateral flow, and coronary stenosis enlargement. Recent work suggests that the nitrates may also act by preventing distal coronary artery or collateral vasoconstriction, which can reduce blood flow downstream from a total coronary obstruction. Thus, there are many anti-ischemic mechanisms of action by which nitroglycerin and the organic nitrates may be beneficial in both acute and chronic ischemic heart disease syndromes. The unique salutory effects of the nitrates in subjects with left ventricular dysfunction or congestive heart failure make these drugs particularly attractive for patients with abnormal systolic function and intermittent myocardial ischemia. Finally, the emergent role of intravenous nitroglycerin in acute myocardial infarction offers new prospects that nitrate therapy may prove to be beneficial in acute myocardial infarction as well as postmyocardial infarction for the reduction of left ventricular remodeling.

Impact of unstable angina on operative mortality with coronary revascularization at varying time intervals after myocardial infarction

We have performed a retrospective study of patients undergoing coronary artery bypass grafting for postinfarction angina in an effort to determine the influence of recency of myocardial infarction and unstable angina on operative mortality. Time from myocardial infarction to bypass was arbitrarily divided into five intervals. Nine hundred ninety-three patients having isolated coronary bypass for postinfarction angina were analyzed, and a significant trend of increased operative mortality with recency of myocardial infarction was found (p less than 0.001). When patients were operated on during the time interval zero to 24 hours after infarction, the operative mortality rate was 18.6%. In the interval from 1 day to 1 week after infarction, the operative mortality rate was 7.4%; 1 week to 3 weeks, 5.9%; and 3 weeks to 3 months, 2.7%. In patients operated on more than 3 months after infarction, the operative mortality rate was 3.9%. The operative mortality rate in 360 patients with postinfarction stable angina was 0.83% compared with 7.3% in 633 patients with postinfarction unstable angina (p less than 0.001). Of 18 risk factors tested, 12 were found by univariate analysis to be independent predictors of operative mortality, including recency of myocardial infarction and unstable angina. Stepwise logistic regression analysis of independent predictive variables revealed that unstable angina, previous surgical revascularization, preoperative hypotension, nonelective surgery, preoperative cardiac arrest, and female sex were the strongest predictors of mortality; recency of myocardial infarction was not a factor. When acute surgical reperfusion is not the primary treatment strategy for patients with myocardial infarction, operative mortality with coronary bypass is increased with the recency of myocardial infarction. The reason for this increase in operative mortality is a patient selection process in which those with persistent or intermittent myocardial ischemia, as reflected in the clinical syndrome of unstable angina, are selected for operation. Unstable angina is a major determinant of operative mortality after myocardial infarction. In patients with stable angina, operative mortality is not increased by the recency of myocardial infarction.

Sudden Death in Congestive Heart Failure

Despite significant advances in recent years in the diagnosis and treatment of congestive heart failure, sudden unexpected cardiac death is still considered a major epidemiologic problem among those patients. This article lists some of the predisposing factors to the development of cardiac arrhythmias and sudden death in patients with congestive heart failure. These include electrolyte or autonomic nervous system inbalance, the use of certain anti-arrhythmic drugs, or intermittent myocardial ischemia. This paper shows that an advanced degree of left ventricular dysfunction and the preference frequent or complex ventricular arrhythmias appear to be major predictors of total and sudden mortality among patients with congestive heart failure. A screening of 24 hours ambulatory Holter monitor recording appears to be useful in identifying patients at risk of sudden cardiac death.

Altered Load Dependence of Postischemic Myocardium

Intermittent myocardial ischemia can produce areas of postischemic ("stunned") myocardium in the heart of the human with coronary artery disease. These areas are no longer ischemic, but have diminished contractile performance. Although the effects of loading conditions on systolic contraction of normal, ischemic, and failing myocardium have been investigated in great detail, the way in which load affects contraction of postischemic myocardium is not known. The aim of this study was to determine in anesthetized dogs how loading conditions affect the systolic function of a region of myocardium after 10 min of ischemia and 1 h of reperfusion. Sets of piezoelectric crystals were implanted in a test zone and in a remote zone of myocardium. Measurements of systolic wall thickening were made during nine combinations of left atrial pressure (3, 6, and 9 cmH2O) and mean arterial pressure (70, 90, and 110 mmHg). One set of measurements was made under baseline conditions, and a second set was made after 10 min of coronary occlusion and 1 h of reperfusion. Ischemia and reperfusion reduced wall thickening in the test zone 36 +/- 3% and diminished the response to increases in preload. In contrast, the response of the test zone to changes in afterload was unchanged. An interaction between the test zone (in which depressed contraction was observed) and the surrounding myocardium (in which enhanced function was observed) produced the appearance of a regional wall motion abnormality as afterload increased. These results emphasize that the load dependence of postischemic myocardium differs from that of normal myocardium and must be taken into account in clinical studies in which regional contraction is used to monitor the heart for ischemia.

Reproducibility and validity of ambulatory ST segment monitoring in patients with chronic stable angina pectoris

Transient ST segment changes are thought to be an indicator of intermittent myocardial ischemia in patients with chronic stable angina pectoris, and ambulatory ECG monitoring is a potentially useful means of quantifying these changes. In order to evaluate their repeatability, the automated analytical system developed in our department was carefully validated. Ambulatory ST segment monitoring was then performed on two occasions, 6 weeks apart, in 16 patients with established chronic stable angina pectoris of at least 1 year's duration. Both periods of monitoring were undertaken after administration of placebo for 2 weeks, and two bipolar ECG leads (CM 5 and CC 5) were monitored on both occasions. The total number (mean ± SEM) of episodes of ST segment depression greater than 1 mm and of 3 minutes' duration or more in 24 hours was 4.9 ± 1.0 and 5.1 ± 1.0 on the first and second recordings ( p = NS), and the total duration of ST segment depression in 24 hours was 83.6 ± 27.7 minutes and 78.9 ± 20.8 minutes, ( p = NS) respectively. The maximal depth of ST segment depression observed during 24 hours was 3.5 ± 0.3 mm and 3.4 ± 0.2 mm, respectively, in lead CM 5 ( p = NS), with similar findings from lead CC 5. These results demonstrate that ambulatory ST segment depression observed during uncontrolled normal daily activity in patients with established chronic stable angina pectoris is reproducible. This technique could provide a valuable method for assessment of antianginal drugs and patterns of ST segment changes during normal daily activities, provided that manual checks to ensure artifact exclusion are used to supplement the automated analysis.

Nifedipine with and without propranolol in the treatment of myocardial ischemia: effect on ventricular arrhythmias and recovery of regional wall function.

Sudden reperfusion of ischemic myocardium has been related to an extension of damage, due to sudden increases in transmembrane calcium fluxes. When the calcium slow channel blocker nifedipine (1 microgram kg-1 min-1 i.v.) was infused just prior to release of a 30 min partial obstruction of the left anterior descending coronary artery (LAD) in anesthetized pigs, recovery of regional function was better (75%) than in untreated animals (50%). The number of reperfusion arrhythmias was also significantly lower in the treated animals. In another series of experiments, ventricular fibrillation occurred in 80% of the untreated animals within 10 min after the complete acute occlusion of the LAD. Animals pretreated with propranolol (0.5 mg kg-1 i.v. bolus + infusion) or nifedipine (0.05 microgram kg-1 min-1 i.c.) showed a similar high incidence of ventricular fibrillation. However, when the administration of these drugs was combined, 60% of the animals survived three periods (10 min) of intermittent myocardial ischemia. When the continuous infusion of nifedipine was preceded by a bolus of 2.0 microgram kg-1, sufficient to abolish systolic wall thickening completely, the incidence of ventricular fibrillation was also reduced. Recovery of regional function was nearly complete in these animals.

Intermittent myocardial ischemia during cardiopulmonary bypass

Intermittent myocardial ischemia during cardiopulmonary bypass