Ultrastructure of cardiomyocytes in the peri-infarct zone during the treatment of experimental myocardial infarct in rats using the hexapeptide dalargin

The experiments on white rats with induced myocardial infarction have studied the influence of dalargin on the infarction size and peri-infarction zone ultrastructure. 24 hours later the decrease in the infarction zone size was detected in rats who had received dalargin in a dose of 50 and 100 micrograms/kg. In the peri-infarction zone the increase in glycogen quantity, the lower degree of lipid infiltration, the increase in mitochondrial number and mitochondrial energy effectiveness coefficient were noted, as compared to control animals. Sarcolemma of cardiomyocytes from the peri-infarction zone in rats on dalargin was impermeable for colloidal lanthanum. The decrease in the infarction size under the effect of dalargin is explained by its influence on the survival of cardiomyocytes in the peri-infarction zone.     

Characteristics of the normal gluconeogenesis effect of prostaglandin F2 alpha and in myocardial infarct

The effect of PGF2 alpha on glucose synthesis de novo in a healthy rat organism and those with coronary occlusion-myocardial infarction was studied. There was observed prostaglandin's metabolic action simultaneously at one direction: there was increased the concentration of non-nitric precursors of gluconeogenesis in blood of animals of both groups, final disintegration product of tissue proteins, the gluconeogenic activity of key enzymes and therefore the concentration of newly formed glucose went up as so as glycogen in liver, cardiac and skeletal muscle. Seemingly, PGF2 alpha stimulates the intensity not only of gluco-, but glyconeogenesis having cardioprotective action. At the same time metabolic effect of PGF2 alpha is strongly marked in coronary occlusion rat with myocardial infarction.     

Changes in the concentration of catecholamines in the organs of animals with experimental myocardial infarcts under the influence of malaben]

The content of adrenaline and noradrenaline in the tissues of the heart, adrenal glands, spleen and brain of rats was studied in experimental myocardial infarction. A significant decrease in the catecholamine levels was revealed in the tissues. Malaben promoted normalization of the catecholamine tissue content in myocardial infarction. It is suggested that the said effect of malaben is due to its antihistaminic properties.     

Correlations between the endothelium-dependent relaxation of the aorta and arterial pressure in rats with myocardial infarction

The effect of experimental myocardial infarction on endothelium-dependent relaxation was studied on isolated rat aorta and compared with the dynamics of arterial pressure (AP). It was shown that the endothelium-dependent relaxation of aorta was increased 1.8 times 3 h following the myocardial infarction. Simultaneously the drop in AP which had begun immediately following the experimental infarction became maximal. In 24 h both the indices were restored practically to the initial level. There was a significant negative correlation between the extent of endothelium-dependent relaxation and AP. It was suggested that the increase in endothelium-dependent relaxation could influence vascular tone, the drop in AP, and, finally, the development of cardiogenic shock in myocardial infarction in man.     

The structuro-functional state of the ischemic myocardium under the action of a terrilitin-nicotinic acid mixture in animal experiments

Histochemical evidence of the activity and distribution of glycolysis redox enzymes, tissue respiration and terminal oxidation pattern (dehydrogenase of lactic, malic, succinic and isocitric acids, NAD-N- and NADPh-N-ase, cytochrome oxidase) as well as the levels of the major carbohydrates (glycogen, neutral aminopolysaccharides, glucose) were experimentally studied in the cardiomyocytes of myocardial necrotic, perinecrotic and intact areas in the control and in the experimental material under the administration of terrilitin-nicotinic acid mixture. It was stated that the use of aforementioned mixture contributed to the retention of enzymatic activity and optimal levels of energy formation in the cardiomyocytes of the marginal infarction zone and noticeably prevented the destructive involvement of the considered area as well as the impairment of functional activity of oscillating cardiomyocytes. Therefore, the application of the mixture improved the outcome prognosis in acute myocardial infarction.     

Alterations in the heart lysosomal stability in isoproterenol induced myocardial infarction in rats

The alterations in the heart lysosomal stability following isoproterenol induced myocardial infarction were studied in albino rats. The rate of release of beta-glucuronidase at various time intervals at 37 degrees C from lysosome rich fraction was taken as a measure of lysosomal stability. As compared to the control day one, three and five samples exhibited a significant increase in beta-glucuronidase activity at all the time intervals. The subcellular distribution of beta-glucuronidase was also studied and the soluble and total activities exhibited an increase at peak infarction stage and returned to normal during the recovery. The decrease in the lysosomal stability might be attributed to the increased beta-glucuronidase activity observed following myocardial infarction.     

Characteristics of the energy of electrostatic interaction of the formed elements of blood in experimental myocardial ischemia]

The diffusion and z-potentials of red cells of the blood outflowing from the zone of myocardial ischemia through the branch of the large cardiac vein were studied during acute period of experimental myocardial infarction. This enabled one to calculate the energy of electrostatic repulsion (EER) between blood constituents and to identify the factors exerting a significant effect on this value in acute experimental myocardial infarction induced in 20 dogs by ligation of the anterior interventricular branch of the left coronary artery. It was shown that the energetic state of the double electric lesion is the leading factor in the changed EER and in manifestation of the aggregation activity by the blood constituents. It was noted that the energetic potentials of red cells of the blood collected from the zone of myocardial ischemia show a statistically significant reduction.     

Cardioprotective effect of cromakalim (potassium channel opener) in isoproterenol induced myocardial infarction in rats.

Animals pretreated with cromakalim (1 mg/kg,po) along with isoproterenol (85 mg/kg,sc) showed less myocardial degenerative changes on histopathological examinations when compared with those treated with isoproterenol alone. Cromakalim's beneficial effects on myocardium were in dose-dependent manner. Administration of cromakalim (po) lowered significantly the serum LDH and SGOT and depleted intracytoplasmic glycogen as demonstrated by periodic schiff staining procedure. Increase in blood clotting time was highly significant (P less than 0.001). The results suggest cardioprotective effect of cromakalim in isoproterenol induced myocardial infarction.     

Elimination of disorders of the electrical stability of the heart in experimental myocardial infarct and postinfarct cardiosclerosis under the influence of a benzodiazepine receptor agonist

It was shown on Wistar male rats that agonist of benzodiazepine receptors phenazepam considerably suppressed the heart ectopic activity and eliminated disturbances of the heart electric stability in acute myocardial infarction and postinfarction cardiosclerosis. The drug prevented to a considerable extent the death rate of animals within the first day following the ligation of coronary artery and the fall of arterial pressure in animals with the acute myocardial infarction. Possible mechanism of the benzodiazepine agonist effect is under discussion.     

Influence of fasting and hormone deficiency on myocardial glycogen levels in rats.

This study was undertaken because of uncertainties regarding the influence of hormones on myocardial glycogen metabolism of fed and fasted rats. The results indicate that adrenal hormones exert a stabilizing effect on myocardial glycogen levels in fed animals but are not necessary for synthesis to occur. Hypophysectomy eliminates the glycogen increase that occurs from fasting in normal animals while insulin deficiency leads to elevated glycogen stores in both fed and fasted conditions. These findings suggest that changes in myocardial glycogen metabolism are the results of a synergetic relationship between a variety of hormonal and nutritional factors.     

Enzyme activity of cardiac glycogen metabolism: study of an in situ hypoxia protocol in the rat

Myocardial hypoxia, induced by arrest of the artificial ventilation of anaesthetized open-chest rats, was utilized in order to study some aspects of the regulation of myocardial glycogen metabolism. Atenolol, a cardioselective beta-adrenergic receptor antagonist, and verapamil, an inhibitor of sarcolemmal calcium transfer, were used to determine the respective role of adenosine 3', 5'-cyclic monophosphate (cAMP) and calcium in the activation of the enzymes of glycogen phosphorolysis and synthesis. Glycogen degradation is reduced by atenolol treatment, as a consequence of a reduced activation of glycogen phosphorylase. Verapamil treatment has no significant effect, neither on the enzyme activation nor on the glycogen utilization. The activation of glycogen synthase, expressed by the conversion of the enzyme from the D to the I form, which results from the decrease in glycogen stores during hypoxia, is lowered under the effect of both drugs. However, in the beta-blocker treatment case, this effect results from a lower glycogen depletion while this effect is more specific in hearts from rats treated with verapamil. Under the effect of verapamil, the reduction of synthase activation, for a similar depletion of glycogen stores, was confirmed by experiments using isolated rat hearts submitted to ischaemia. These results show that: 1. the glycogenolysis in the hypoxic myocardium in situ is mainly controlled by a cAMP-dependent enzyme conversion or by metabolic allosteric effectors; 2. the activation of myocardial glycogen synthase, which is essentially correlated to the reduction of glycogen stores, is also calcium-dependent and most probably totally cAMP-independent.     

Enhanced Glycogen Storage of a Subcellular Hot Spot in Human Skeletal Muscle during Early Recovery from Eccentric Contractions

Unaccustomed eccentric exercise is accompanied by muscle damage and impaired glucose uptake and glycogen synthesis during subsequent recovery. Recently, it was shown that the role and regulation of glycogen in skeletal muscle are dependent on its subcellular localization, and that glycogen synthesis, as described by the product of glycogen particle size and number, is dependent on the time course of recovery after exercise and carbohydrate availability. In the present study, we investigated the subcellular distribution of glycogen in fibers with high (type I) and low (type II) mitochondrial content during post-exercise recovery from eccentric contractions. Analysis was completed on five male subjects performing an exercise bout consisting of 15 x 10 maximal eccentric contractions. Carbohydrate-rich drinks were subsequently ingested throughout a 48 h recovery period and muscle biopsies for analysis included time points 3, 24 and 48 h post exercise from the exercising leg, whereas biopsies corresponding to prior to and at 48 h after the exercise bout were collected from the non-exercising, control leg. Quantitative imaging by transmission electron microscopy revealed an early (post 3 and 24 h) enhanced storage of intramyofibrillar glycogen (defined as glycogen particles located within the myofibrils) of type I fibers, which was associated with an increase in the number of particles. In contrast, late in recovery (post 48 h), intermyofibrillar, intramyofibrillar and subsarcolemmal glycogen in both type I and II fibers were lower in the exercise leg compared with the control leg, and this was associated with a smaller size of the glycogen particles. We conclude that in the carbohydrate-supplemented state, the effect of eccentric contractions on glycogen metabolism depends on the subcellular localization, muscle fiber’s oxidative capacity, and the time course of recovery. The early enhanced storage of intramyofibrillar glycogen after the eccentric contractions may entail important implications for muscle function and fatigue resistance.     

Role of sodium-calcium exchanger in the myocardial protection against ischemia-reperfusion injury

Present study was aimed at investigation into the role of sodium-calcium exchanger (NCX) in myocardial ischemia-reperfusion injury and ischemic preconditioning (IPC). Experiments were performed in vivo rat model of regional myocardial ischemia-reperfusion. It was shown that inhibition of reverse mode of NCX with selective blocker KB-R7943 at a dose of 10 mg/kg resulted in significant decrease in occurrence and severity of ischemic ventricular tachyarrhythmias. Furthermore, administration of KB-R7943 caused potentiation of the antiarrhythmic effect exerted by single episode of IPC. However, KB-R7943 exerted no effect on myocardial infarction size nor affected infarction size limitation by IPC. In conclusion, inhibition of reverse mode of NCX conferred significant antiarrhythmic effect against ischemic rhythm disorders but it was ineffective in terms of infarction size limitation.     

大鼠心肌梗死模型构建和评价方法的改良

目的 优化和改良大鼠心肌梗死模型的构建和评价方法,提高模型的可靠性和稳定性.方法 取雄性SD大鼠结扎左冠状动脉前降支建立心肌梗死模型,在模型的构建过程中从麻醉、插气管、保温、手术操作、术后护理等环节进行优化和改进,并观察不同的麻醉方法和术后时间对心肌梗死程度的影响,用不同的染色方式进行心肌梗死模型的评价.结果 对比大鼠心肌梗死模型构建过程中各组大鼠麻醉时间、术后恢复以及心肌梗死面积的结果,戊巴比妥钠是更合适的麻醉药;结扎手术后时间对模型心肌梗死范围无明显影响（P＆gt;0.05）,但心肌缺血危险区面积随术后时间的延长明显减少（P〈0.01）;TTC与依文思蓝双重染色相对TTC染色能明显观察到心肌缺血危险区和梗死区范围.结论 优化和改进后的大鼠心肌梗死模型,提高了动物福利,制备和评价方法更加客观准确.     

Effect of adaptation to short-term stress exposure on the fibrillation threshold and ectopic activity of the heart in experimental myocardial infarct

Preliminary adaptation to short-term stress was shown to prevent the decrease in the heart fibrillation threshold and an increase in ectopic activity which is usually observed in experimental myocardial infarction. This protective effect involves an enhanced activity of the antioxidant system. Therefore, a synthetic antioxidant ionol was applied to prevent disturbances of the heart electrical stability in infarction. It was established that ionol completely prevents the decrease in the electrical threshold and the increase in ectopic activity of the heart in experimental infarction. Thus, it can be concluded that ionol possesses an antiarrhythmic effect.     

Resistance of the myocardium to ischemia and efficacy of myocardial preconditioning in experimental diabetes mellitus

Data on myocardial tolerance of ischemia in the animals with experimental diabetes are controversial. In our study, myocardial sensitivity to ischemia and infarction-limiting effect of ischemic preconditioning have been investigated in the in vivo rat model of myocardial infarction in alloxan-induced insulin-dependent diabetes mellitus. It has been shown that in 6 weeks after alloxan injection in the diabetic rats infarction size as determined by TTC staining was significantly smaller than in healthy controls (39.8 +/- 8.8 and 62.3 +/- 6.6%, respectively, p < 0.01). Also, occurrence of ischemic tachyarrhythmias was more rare in diabetic rats than in controls. A single episode of ischemic preconditioning in diabetic rats showed a much lesser protection against infarction than in controls. Therefore, the data obtained support the existence of endogenous protective myocardial phenotype in diabetes, although the effectiveness of ischemic preconditioning in diabetes is reduced.     

Glycogen phosphorylase isoenzyme BB in diagnosis of myocardial ischaemic injury and infarction

This review deals with glycogen phosphorylase (GP) and its isoenzyme BB in the diagnosis of ischaemic myocardial injury. Early identification and confirmation of acute myocardial infarction is essential for correct patient care and disposition decision in the emergency department. In this respect, glycogen phosphorylase isoenzyme BB (GPBB) based on its metabolic function is an enzyme for early laboratory detection of ischaemia. In the aerobic heart muscle GPBB together with glycogen is tightly associated with the vesicles of the sarcoplasmic reticulum. Release of GPBB, the main isoform in the human myocardium, essentially depends on the degradation of glycogen, which is catalyzed by GP. Ischaemia is known to favour the conversion of bound GP in the b form into GP a, thereby accelerating glycogen breakdown, which is the ultimate prerequisite for getting GP into a soluble form being able to move freely in the cytosol. The efflux of GPBB into the extracellular fluid follows if ischaemia-induced structural alterations in the cell membrane become manifest. The clinical application of GPBB as a marker of ischaemic myocardial injury is a very promising tool for extending our knowledge of the severity of myocardial ischaemic events in the various coronary syndromes. The rational roots of this development were originated from Albert Wollenberger's research work on the biochemistry of cardiac ischaemia and the transient acceleration of glycogenolysis mainly brought about by GP activation.     

Effect of cordarone on the ultrastructure of cardiac muscle cells in experimental myocardial infarct

The effect of cordarone on the ultrastructure of cardiomyocytes of the periinfarction zone was studied in experiments on 30 cats. Cordarone was injected intramuscularly daily for 3.7 and 15 days in a dose of 10 mg/kg. Experimental myocardial infarction was induced by ligation of the left coronary artery at the border of its medium and inferior thirds. As compared with control, cordarone produced a more demonstrable reduction in the intracellular edema, more rapid recovery of the structure of myofibrils and greater accumulation of glycogen granules by the cytoplasm of cardiomyocytes. At the same time the structure of the mitochondria returned to normal more slowly as compared with control, with persistent widening of the cisternae of the sarcoplasmic reticulum being observed in addition. The changes described indicate that cordarone exerts different actions on the ultrastructure of cardiomyocytes, which is probably based on the drug influence on adrenergic processes and calcium turnover in the myocardium.     

Seasonal variations in the myocardial infarction incidence and possible effects of geomagnetic micropulsations on the cardiovascular system in humans

The analysis of the ambulance calls in Moscow, related to myocardial infarction (85.000 events), sudden death (71.700 events), and hypertension crises (165.500 events) over the period of 1979-1981 demonstrated their clear seasonal variations with a profound summer minimum and a winter maximum. The same results were obtained in the analysis of statistical monthly data on sudden death from infarction in Bulgaria over the period of 15 years (1970-1985). However, there are a great number of clinical and statistical studies confirming the rises in the incidence of myocardial infarction, hypertension crise, and sudden death during geomagnetic disturbances, which have maximum occurrence near equinox, not in winter. In order to explain this contradiction, we suggested that one of critical factors that affect the human cardiovascular system is geomagnetic micropulsations Pc1 having the frequency comparable with the frequency of heart rate beatings and winter maximum in their occurrence. The results of a comparative analysis of data of ambulance calls in Moscow related to myocardial infarction and sudden death and the catalog of Pc1 observations at the geophysical observatory "Borok" (Yaroslavl region) are presented. It is shown that in approximately 70% of days with an anomalously large number of ambulance calls related to myocardial infarction, Pc1 micropulsations have been registered. The probability of simultaneous occurrence of myocardial infarction and Pc1 in the winter season was 1.5 times greater than their accidental coincidence. Moreover, it was found that in winter the effects of magnetic storms and Pc1 IM(A) were much higher than in summer. We suggested that one of possible reasons for the seasonal variations in the occurrence of myocardial infarction is an increase in the production of the pineal hormone melatonin in winter which leads to an unstable state of the human organism and an increase in its sensitivity to the effect of geomagnetic pulsations.     

Impact of low-flow ischemia on substrate oxidation and glycolysis in the isolated perfused rat heart

Interventions that stimulate carbohydrate oxidation appear to be beneficial in the setting of myocardial ischemia or infarction. However, the mechanisms underlying this protective effect have not been defined, in part because of our limited understanding of substrate utilization under ischemic conditions. Therefore, we used (1)H and (13)C NMR spectroscopy to investigate substrate oxidation and glycolytic rates in a global low-flow model of myocardial ischemia. Isolated male Sprague-Dawley rat hearts were perfused for 30 min under conditions of normal flow (control) and low-flow ischemia (LFI, 0.3 ml/min) with insulin and (13)C-labeled lactate, pyruvate, palmitate, and glucose at concentrations representative of the physiological fed state. Despite a approximately 50-fold reduction in substrate delivery and oxygen consumption, oxidation of all exogenous substrates plus glycogen occurred during LFI. Oxidative metabolism accounted for 97% of total calculated ATP production in the control group and approximately 30% in the LFI group. For controls, lactate oxidation was the major source of ATP; however, in LFI, this shifted to a combination of oxidative and nonoxidative glycogen metabolism. Interestingly, in the LFI group, anaplerosis relative to citrate synthase increased sevenfold compared with controls. These results demonstrate the importance of oxidative energy metabolism for ATP production, even during very-low-flow ischemia. We believe that the approach described here will be valuable for future investigations into the underlying mechanisms related to the protective effect of increasing cardiac carbohydrate utilization and may ultimately lead to identification of new therapeutic targets for treatment of myocardial ischemia.