Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low-28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Hemostatic triggers of myocardial infarction

The occurrence of acute ischemia in the coronary circulation, leading to myocardial infarction and sudden cardiac death and numerous other thromboembolic events in different areas of the body, follows a circadian periodic pattern. This pattern is characterized by a major peak in the morning. Numerous circadian rhythms in different compartments of the hemostatic system contribute to this characteristic pattern. The temporal coincidence of vascular rhythms favoring impairment of the coronary circulation, with a morning increase in the activity of platelets in response to stimulation with a hypercoagulable state and a circadian minimum in fibrinolysis, leads to the increased incidence of thromboembolic events at that circadian stage. Direct circadian clock-dependence has been shown for some rhythms, e.g. in fibrinolysis, and circadian rhythm disturbances may favor coronary artery pathology. The circadian transient risk state for myocardial infarctions and other thromboembolic events during the morning hours in diurnally active subjects has to be recognized and may be amenable to possible prevention. If an event has occurred, some of the hemostatic rhythms operative in this condition may also affect treatment.     

The discovery of the selective If current inhibitor ivabradine (Procoralan): a new therapeutic approach to ischemic heart disease

Coronary artery disease is still a major cause of morbidity and mortality in the industrialized countries and its prevalence is predicted to grow with the current aging of the population in these countries. In spite of the rapid pace of progress and increasing use of myocardial revascularization procedures, in particular percutaneous coronary interventions, the medical treatment of coronary artery disease has lost none of its relevance in the majority of patients, though conventional drugs have their limitations and the pharmacological approach to ischemic heart disease needs to be improved in terms of efficacy and tolerance to ensure better prevention of mortality and improvement in quality of life. Since increased heart rate plays a major role in coronary artery disease, not only as a trigger of most ischemic episodes, but also as an independent predictor of mortality, inhibition of the pacemaker If current in view of inducing a direct and selective decrease in heart rate represents an ideal conceptual target and an attractive therapeutic approach to coronary artery disease. The screening of original benzocycloalkane compounds at the Servier Research Institute resulted in the selection of ivabradine (Procoralan) for clinical development. Preclinical data showed that ivabradine inhibits the If current originating in the sinus node, induces a selective reduction in heart rate both at rest and during exercise, preserves myocardial contractility, atrioventricular conduction and ventricular repolarization and prevents exercise-induced myocardial ischemia as effectively as a b-blocker while offering better protection of regional myocardial contractility. These data were confirmed in humans, in particular the anti-ischemic efficacy of ivabradine, at least as effective as that of a b-blocker in patients with stable angina. Large ongoing clinical trials are seeking to assess the therapeutic value of ivabradine in ischemic heart failure and its potential for improving the prognosis of coronary artery disease by reducing mortality and the occurrence of major cardiovascular events.     

Intrinsic defensive mechanisms in the heart: a potential novel approach to cardiac protection against ischemic injury

Despite recent advances in pharmacotherapy of coronary artery disease and interventional cardiology, the management of myocardial ischemia still remains a major challenge for basic scientists and clinical cardiologists. An urgent need to combat ischemic heart disease, its forms, such as infarction, and complications including sudden cardiac death led to the development of an alternative strategy of myocardial protection based on the exploitation of the heart's own intrinsic protective mechanisms. A new concept relies on the evidence that the heart is able to protect itself by way of adaptation, either short-term or long-term, to transient episodes of stress (e.g., ischemia, hypoxia, free oxygen radicals, heat stress, etc.) preceding sustained ischemia. Preconditioning by brief episodes of ischemia (ischemic preconditioning, IP) represents the most powerful cardioprotective phenomenon. Apart from the short-lasting protection afforded by classical IP or its delayed ("second window") phase, adaptation to long-lasting physiological stimuli or pathological processes is also known to increase myocardial resistance to ischemic injury. Although molecular mechanisms of cardiac adaptation conferring a higher ischemic tolerance still remain not sufficiently elucidated, multiple cascades of intracellular signalization are suggested to be involved in this process. Experimental studies led to the observations that pharmacological modulations at different levels of signal transduction might mimic protective effects of the adaptive phenomena and thus provide a safer way of inducing cardioprotection in humans.     

Effect of repeated episodes of reversible myocardial ischemia on myocardial blood flow and function in humans

Nine patients with coronary artery disease and normal left ventricular (LV) function underwent two episodes of dobutamine-induced ischemia to determine whether repeated episodes of ischemia lead to cumulative stunning. Positron emission tomography (PET) and oxygen 15-labeled H(2)O was used to assess myocardial blood flow (MBF) at baseline, peak stress, and after stress for each ischemic episode. Quantitative echocardiographic assessment of global ejection fraction (EF) and regional systolic function (SF) was performed at rest and regular intervals after dobutamine. SF was assessed for regions subtended by a coronary artery with a >70% diameter stenosis. Both EF and SF were more severely impaired 45 min after the second episode of stress compared with 45 min after the first (both P < 0.01), despite no difference in duration of the two dobutamine infusions or MBF at peak stress (1.72 vs. 1.69). After both episodes of ischemia, when LV function was impaired but subsequently recovered, MBF (1.15 +/- 0.39 and 1.20 +/- 0.43, respectively) was no different to baseline MBF (1.02 +/- 0.35), confirming that repeated episodes of dobutamine-induced ischemia lead to cumulative myocardial stunning.     

动态心电图对无症状性心肌缺血的诊断价值

目的:研究动态心电图对无症状性心肌缺血的临床诊断价值。方法:收集我院2014年6月-2015年6月我院接受诊治的冠心病(CAD)患者120例作为研究对象,采用动态心电图仪检测记录24h心电图信息,将动态心电图检测为心肌缺血的患者分为A组(无症状心肌缺血)、B组(有症状心肌缺血),比较两组患者基本信息、心肌缺血发作阵次、ST段下降幅度、ST段下降持续时间、心肌缺血阈变异性、心率及心率失常发生率。结果:120例CAD患者中有95例患者出现心肌缺血,其中A组66例(占69.47%),B组29例(占30.53%),差异显著(P0.05)。A组ST段阵次改变明显高于B组,A组ST段下降幅度、ST段下降持续时间、心肌缺血阈变异性明显低于B组(P0.05)。A、B两组患者心肌缺血发作表现出昼夜节律,在时间段6:00-12:00最高,在时间段0:00-6:00最低(P0.05)。A组患者平均心率显著低于B组患者,心律失常发生率显著高于B组(P0.05)。结论:动态心电图能够准确的诊断出无临床症状心肌缺血,使患者得到及时的治疗,值得临床推广应用。     

Naloxone reversal of ischemic arrhythmia is stereospecific and suggests role of endogenous opioid peptides in ischemic heart disease.

The effects of the stereoisomers of naloxone during myocardial ischemia were studied. (-)-Naloxone (but not the (+)-isomer naloxone) attenuated the ischemia-induced cardiac arrhythmias, hypotension, and bradycardia that result from coronary artery occlusion in anesthetized rats. From these findings, it may be inferred that endogenous opioid peptides may play a role in the pathophysiology of myocardial ischemia. It is also suggested that naloxone may have therapeutic value in the prevention and treatment of ischemic heart disease.     

beta1-Adrenoreceptor activation contributes to ischemia-reperfusion damage as well as playing a role in ischemic preconditioning

Protein kinase A (PKA) activation has been implicated in early-phase ischemic preconditioning. We recently found that during ischemia PKA activation causes inactivation of cytochrome-c oxidase (CcO) and contributes to myocardial damage due to ischemia-reperfusion. It may be that beta-adrenergic stimulation during ischemia via endogenous catecholamine release activates PKA. Thus beta-adrenergic stimulation may mediate both myocardial protection and damage during ischemia. The present studies were designed to determine the role of the beta(1)-adrenergic receptor (beta(1)-AR) in myocardial ischemic damage and ischemic preconditioning. Langendorff-perfused rabbit hearts underwent 30-min ischemia by anterior coronary artery ligation followed by 2-h reperfusion. Occlusion-reperfusion damage was evaluated by delineating the nonperfused volume of myocardium at risk and volume of myocardial necrosis after 2-h reperfusion. In some hearts ischemic preconditioning was accomplished by two 5-min episodes of global low-flow ischemia separated by 10 min before coronary occlusion-reperfusion. Orthogonal electrocardiograms were recorded, and coronary flow was monitored by a drip count. Three hearts from each experimental group were used to determine mitochondrial CcO and aconitase activities. Two-hour reperfusion after occlusion caused an additional decrease in CcO activity vs. that after 30-min occlusion alone. Blocking the beta(1)-AR during occlusion-reperfusion reversed CcO activity depression and preserved myocardium at risk for necrosis. Similarly, mitochondrial aconitase activity exhibited a parallel response after occlusion-reperfusion as well as for the other interventions. Furthermore, classic ischemic preconditioning had no effect on CcO depression. However, blocking the beta(1)-AR during preconditioning eliminated the cardioprotection. If the beta(1)-AR was blocked after preconditioning, the myocardium was preserved. Interestingly, in both of the latter cases the depression in CcO activity was reversed. Thus the beta(1)-AR plays a dual role in myocardial ischemic damage. Our findings may lead to therapeutic strategies for preserving myocardium at risk for infarction, especially in coronary reperfusion intervention.     

Nonlinear Heart Rate Variability features for real-life stress detection. Case study: students under stress due to university examination

Background

Elevated transient ischemic ST segment episodes in the ambulatory electrocardiographic (AECG) records appear generally in patients with transmural ischemia (e. g. Prinzmetal's angina) while depressed ischemic episodes appear in patients with subendocardial ischemia (e. g. unstable or stable angina). Huge amount of AECG data necessitates automatic methods for analysis. We present an algorithm which determines type of transient ischemic episodes in the leads of records (elevations/depressions) and classifies AECG records according to type of ischemic heart disease (Prinzmetal's angina; coronary artery diseases excluding patients with Prinzmetal's angina; other heart diseases).

Methods

The algorithm was developed using 24-hour AECG records of the Long Term ST Database (LTST DB). The algorithm robustly generates ST segment level function in each AECG lead of the records, and tracks time varying non-ischemic ST segment changes such as slow drifts and axis shifts to construct the ST segment reference function. The ST segment reference function is then subtracted from the ST segment level function to obtain the ST segment deviation function. Using the third statistical moment of the histogram of the ST segment deviation function, the algorithm determines deflections of leads according to type of ischemic episodes present (elevations, depressions), and then classifies records according to type of ischemic heart disease.

Results

Using 74 records of the LTST DB (containing elevated or depressed ischemic episodes, mixed ischemic episodes, or no episodes), the algorithm correctly determined deflections of the majority of the leads of the records and correctly classified majority of the records with Prinzmetal's angina into the Prinzmetal's angina category (7 out of 8); majority of the records with other coronary artery diseases into the coronary artery diseases excluding patients with Prinzmetal's angina category (47 out of 55); and correctly classified one out of 11 records with other heart diseases into the other heart diseases category.

Conclusions

The developed algorithm is suitable for processing long AECG data, efficient, and correctly classified the majority of records of the LTST DB according to type of transient ischemic heart disease.     

Chronotherapy in Coronary Heart Disease: Comparison of Two Nitrate Treatments

The purpose of this study was to assess the ischemic burden and the hemodynamic changes during daily activities in patients with coronary heart disease. Three exercise tests were performed during the day (10:00 a.m., 2:00 p.m., 6:00 p.m.), recording ST-segment depression, pulmonary artery pressure, pulmonary wedge pressure, and cardiac output as well as heart rate and systemic blood pressure during placebo and nitrate therapy. With placebo as well as nitrate therapy there was a gradual increase of ischemia and preload and a decrease of cardiac output during the day. High nitrate concentrations led to a significant reduction of both preload and ST depression with a marked circadian phase dependency of cardiovascular effects.     

Chronotherapy in Coronary Heart Disease: Comparison of Two Nitrate Treatments

The purpose of this study was to assess the ischemic burden and the hemodynamic changes during daily activities in patients with coronary heart disease. Three exercise tests were performed during the day (10:00 a.m., 2:00 p.m., 6:00 p.m.), recording ST-segment depression, pulmonary artery pressure, pulmonary wedge pressure, and cardiac output as well as heart rate and systemic blood pressure during placebo and nitrate therapy. With placebo as well as nitrate therapy there was a gradual increase of ischemia and preload and a decrease of cardiac output during the day. High nitrate concentrations led to a significant reduction of both preload and ST depression with a marked circadian phase dependency of cardiovascular effects.     

Statins enhance clonal growth of late outgrowth endothelial progenitors and increase myocardial capillary density in the chronically ischemic heart

Background

Coronary artery disease and ischemic heart disease are leading causes of heart failure and death. Reduced blood flow to heart tissue leads to decreased heart function and symptoms of heart failure. Therapies to improve heart function in chronic coronary artery disease are important to identify. HMG-CoA reductase inhibitors (statins) are an important therapy for prevention of coronary artery disease, but also have non-cholesterol lowering effects. Our prior work showed that pravastatin improves contractile function in the chronically ischemic heart in pigs. Endothelial progenitor cells are a potential source of new blood vessels in ischemic tissues. While statins are known to increase the number of early outgrowth endothelial progenitor cells, their effects on late outgrowth endothelial progenitor cells (LOEPCs) and capillary density in ischemic heart tissue are not known. We hypothesized that statins exert positive effects on the mobilization and growth of late outgrowth EPCs, and capillary density in ischemic heart tissue.

Methodology/Principal Findings

We determined the effects of statins on the mobilization and growth of late outgrowth endothelial progenitor cells from pigs. We also determined the density of capillaries in myocardial tissue in pigs with chronic myocardial ischemia with or without treatment with pravastatin. Pravastatin therapy resulted in greater than two-fold increase in CD31+ LOEPCs versus untreated animals. Addition of pravastatin or simvastatin to blood mononuclear cells increased the number of LOEPCs greater than three fold in culture. Finally, in animals with chronic myocardial ischemia, pravastatin increased capillary density 46%.

Conclusions

Statins promote the derivation, mobilization, and clonal growth of LOEPCs. Pravastatin therapy in vivo increases myocardial capillary density in chronically ischemic myocardium, providing an in vivo correlate for the effects of statins on LOEPC growth in vitro. Our findings provide evidence that statin therapy can increase the density of capillaries in the chronically ischemic heart.     

Effect of superoxide dismutase and catalase on myocardial energy metabolism during ischemia and reperfusion

Survival of cardiac patients undergoing heart surgery depends critically upon the recovery of myocardial energy metabolism during reperfusion of ischemic myocardium. The present study compares various parameters of myocardial energy metabolism using an isolated in situ pig heart. The left anterior descending (LAD) coronary artery was occluded for 60 min, followed by 60 min of global hypothermic cardioplegic arrest and 60 min of reperfusion. Free radical scavengers [superoxide dismutase SOD and catalase] were used to protect the ischemic heart from reperfusion injury. In both control and SOD plus catalase-treated groups, ATP, creatine phosphate (CP), ATP/ADP ratio, energy charge and phosphorylation potential dropped significantly during ischemic insult. After reperfusion, CP, ATP/ADP ratio and phosphorylation potential improved significantly, but they were restored to control level only in treated animals. In either case, free energy of ATP hydrolysis (delta G) lowered only by 5% during ischemia, but recovered promptly upon reperfusion. SOD and catalase also improved coronary blood flow and reduced creatine kinase release compared to those of untreated animals, suggesting improved myocardial recovery upon reperfusion. Our results suggest that SOD and catalase significantly improve the myocardial recovery during reperfusion by enhancing rephosphorylation steps, and the value of delta G is more critical compared to those of ATP and CP for myocardial recovery.     

Preconditioning of heart by repeated stunning. Adaptive modification of antioxidative defense system.

Previous studies demonstrated that preconditioning of a heart by repeated stunning can reduce the cellular injury to the heart from subsequent acute ischemic insult. To examine the possible biochemical mechanism for such myocardial preservation afforded by preconditioning, swine heart was subjected to four episodes of 5 min. stunning by occluding the left anterior descending coronary artery (LAD), followed by 10 min. of reperfusion after each stunning. Heart was then made regionally ischemic for 60 min. by LAD occlusion, followed by 6 hrs. reperfusion. Control heart was perfused for 60 min., followed by 60 min. ischemia and 6 hrs. reperfusion. The results of our studies indicated the stimulation of a number of antioxidative enzymes, including Mn-superoxide dismutase (Mn-SOD), catalase, glutathione peroxidase, and glutathione reductase, after repeated stunning and reperfusion. In addition, a number of new proteins were expressed after preconditioning the heart, including some oxidative-stress related proteins and 72 kDa heat-shock protein. These results suggest that preconditioning of a heart by repeated stunning may lead to strengthening of the oxidative defense system of the heart, which is likely to play a role in myocardial preservation during subsequent ischemic and reperfusion injury.     

Reduction of tissue noradrenaline content in the isolated perfused rat heart during ischemia: importance of monoamine oxidation.

The effect of ischemia on myocardial noradrenaline concentration and endogenous noradrenaline output was studied in the isolated perfused rat heart. Following a 15-min stabilization period, regional ischemia was produced by coronary artery ligation. After 60 min of ischemia, noradrenaline concentrations were significantly reduced in the interventricular septum and left ventricle but not in the right ventricle. The reduction in tissue noradrenaline concentration was not prevented when the 60-min ischemia was replaced by a 10-min ischemia followed by a 50-min perfusion. No modification in noradrenaline output was observed during a 60-min ischemia. In contrast, reperfusion was accompanied by a washout of noradrenaline in the coronary effluent, corresponding to only 2% of the amount lost by the tissue. The effect of monoamine oxidase inhibition during the whole ischemic period was studied by perfusing the preparation with pargyline starting 10 min before the artery ligation. Although the administration of pargyline did not alter the noradrenaline output, it did prevent a reduction in myocardial noradrenaline concentration. It was concluded that monoamine oxidase may contribute to the elimination of the noradrenaline lost by the cardiac tissue during ischemia.     

Autophagy in ischemic preconditioning and hibernating myocardium

Autophagy is a major protective mechanism and has been identified in response to hypoxia and more recently, myocardial ischemia, but it is not known whether it is involved in mediating ischemic preconditioning, the most powerful intervention known to protect myocardium against lethal ischemic injury. We examined autophagy in several models of preconditioning induced by 6 repetitive episodes of ischemia every 12 hours versus classical first or second-window preconditioning in swine. The results indicated that autophagy is an important mechanism mediating cardioprotection following repetitive episodes of coronary stenosis or coronary occlusion, but less for traditional first or second window preconditioning.     

Coronary microcirculatory vasoconstriction is heterogeneously distributed in acutely ischemic myocardium

The classical model of coronary physiology implies the presence of maximal microcirculatory vasodilation during myocardial ischemia. However, Doppler monitoring of coronary blood flow (CBF) documented severe microcirculatory vasoconstriction during pacing-induced ischemia in patients with coronary artery disease. This study investigates the mechanisms that underlie this paradoxical behavior in nine patients with stable angina and single-vessel coronary disease who were candidates for stenting. While transstenotic pressures were continuously monitored, input CBF (in ml/min) to the poststenotic myocardium was measured by Doppler catheter and angiographic cross-sectional area. Simultaneously, specific myocardial blood flow (MBF, in ml.min(-1).g(-1)) was measured by 133Xe washout. Perfused tissue mass was calculated as CBF/MBF. Measurements were obtained at baseline, during pacing-induced ischemia, and after stenting. CBF and distal coronary pressure values were also measured during pacing with intracoronary adenosine administration. During pacing, CBF decreased to 64 +/- 24% of baseline and increased to 265 +/- 100% of ischemic flow after adenosine administration. In contrast, pacing increased MBF to 184 +/- 66% of baseline, measured as a function of the increased rate-pressure product (r = 0.69; P < 0.05). Thus, during pacing, perfused myocardial mass drastically decreased from 30 +/- 23 to 12 +/- 11 g (P < 0.01). Distal coronary pressure remained stable during pacing but decreased after adenosine administration. Stenting increased perfused myocardial mass to 39 +/- 23 g (P < 0.05 vs. baseline) as a function of the increase in distal coronary pressure (r = 0.71; P < 0.02). In conclusion, the vasoconstrictor response to pacing-induced ischemia is heterogeneously distributed and excludes a tissue fraction from perfusion. Within perfused tissue, the metabolic demand still controls the vasomotor tone.     

Prospect of Stress Testing

A new method for analyzing the data of stress electrocardiography, based on physiologically justified approximations of trends in the heart rate (HR) and ST, is discussed. The method makes it possible to determine how the HR and ST of an individual vary with time during graded exercise and how these parameters and the times of their regulation depend on the workload; to reveal general patterns of their behavior; and to derive new physiological characteristics. Analysis of the general patterns of only the load time dependences of HR and ST and of the workload dependence of HR in patients with ischemic heart disease allows us to detect brief episodes of myocardial ischemia; to assess the anaerobic thresholds of locally injured areas of the myocardium and of the whole body; and to propose unified parameters for assessing the coronary reserve, the physical working capacity, and the severity of ischemic injury to the myocardium. The proposed method of analysis of stress electrocardiographic data and the combined use of stress electrocardiography, positron emission tomography, myocardial scintigraphy, and stress echocardiography offer new opportunities for a better understanding of myocardial ischemia.     

Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning

Remote ischemic preconditioning reduces myocardial infarction (MI) in animal models. We tested the hypothesis that the systemic protection thus induced is effective when ischemic preconditioning is administered during ischemia (PerC) and before reperfusion and examined the role of the K(+)-dependent ATP (K(ATP)) channel. Twenty 20-kg pigs were randomized (10 in each group) to 40 min of left anterior descending coronary artery occlusion with 120 min of reperfusion. PerC consisted of four 5-min cycles of lower limb ischemia by tourniquet during left anterior descending coronary artery occlusion. Left ventricular (LV) function was assessed by a conductance catheter and extent of infarction by tetrazolium staining. The extent of MI was significantly reduced by PerC (60.4 +/- 14.3 vs. 38.3 +/- 15.4%, P = 0.004) and associated with improved functional indexes. The increase in the time constant of diastolic relaxation was significantly attenuated by PerC compared with control in ischemia and reperfusion (P = 0.01 and 0.04, respectively). At 120 min of reperfusion, preload-recruitable stroke work declined 38 +/- 6% and 3 +/- 5% in control and PerC, respectively (P = 0.001). The force-frequency relation was significantly depressed at 120 min of reperfusion in both groups, but optimal heart rate was significantly lower in the control group (P = 0.04). There were fewer malignant arrhythmias with PerC during reperfusion (P = 0.02). These protective effects of PerC were abolished by glibenclamide. Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a K(ATP) channel-dependent mechanism. Understanding this process may have important therapeutic implications for a range of ischemia-reperfusion syndromes.     

Effect of phosphocreatine and related compounds on the phospholipid metabolism of ischemic heart

Changes in the content of lysophosphoglycerides in a crude plasmalemmal fraction of canine heart during short-term ischemia (occlusion of the left descending coronary artery for 8 min) have been studied in the presence and in the absence of phosphocreatine and phosphocreatinine. In the control experiments without PCr or PCr-nine ischemia caused significant elevation of the content of LPG: that of lysophosphatidylcholine was increased by 83% and that of lysophosphatidylethanolamine by 168%. Intravenous administration of PCr and PCr-nine in doses of 300 mg/kg completely prevented accumulation of LPG in the ischemic zone. Because of the well-known arrhythmogenic properties of LPG, the inhibitory effect of PCr and PCr-nine on the elevation of their concentration in the ischemic zone may be closely related to the antiarrhythmic action of PCr and PCr-nine in acute myocardial ischemia.