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To study the relative roles of creatine kinase (CK) and adenylate systems in cardiac energy turnover, the effect of CK inhibitor, iodoacetamide- (IAA, 0.5 mM), and 2-deoxyglucose-(DOG, 2 mM) induced) 65% depletion of adenine nucleotides at slightly decreased CK flux was determined in isolated rat heart. Both substances did not substantially affect contractile parameters of the isovolumic heart. However, an augmentation of cardiac work induced by isoproterenol addition was feeble and transient in IAA-treated hearts while the response of DOG-treated hearts was well preserved. The cardiac failure after IAA treatment was associated with irreversible fall in myocardial ATP content as evidenced by 31P-NMR technique. Furthermore, these hearts were unable to perform cardiac pump function due to insufficient cardiac filling and distensibility. The DOG-treated hearts exhibited 50% reduction in the pump function and were able to increase their work in elevated resistance. The results suggest that CK pathway is extremely important for both full cardiac relaxation and maximal contractile function.

The cardiac output of isolated working rat heart and left ventricular pressure were estimated in either almost complete inhibition of creatine kinase by iodoacetamide or predominant fall in adenine nucleotides (AdN) content induced by 2-deoxyglucose treatment. In the former case, a profound cardiac pump failure was observed despite almost normal levels of myocardial AdN and phosphocreatine. Those hearts could not maintain the aortic output at standard load due to lower LV systolic pressure, that was accompanied by increased minimal and maximal diastolic pressures by 5-7 mm Hg as well as by LV diastolic stiffness. As LV systolic pressure in those hearts was unchanged in retrogradely perfused and unloaded hearts it might be suggested that the cardiac pump failure was caused by the decreased LV distensibility. On the contrary, deoxyglucose treatment that resulted in 70% fall in the AdN content was accompanied by only moderate reduction of the cardiac output and insignificant changes in LV diastolic pressure and stiffness. The results suggested that creatine kinase plays a crucial role in the maintenance of normal myofibrillar compliance, which is necessary for cardiac filling and pump function.

It is shown that in rabbits subjected to an electric stimulation of the aortic arch there developed concurrently with depletion of tissular norepinephrine reserves in the myocardium also gross metabolic disorders. A preliminary introduction of the drug izm-611 by blocking central alpha-adrenoreseptors at the same time prevented depletion of the tissular norepinephrine reserves and development of disturbances of the energy exchange in the myocardium caused by its neurogenic damage.

The effect of aethimizol, introduced to rabbits before and after inflicting a 3-hours long extraordinary stimulation applied to the reflexogenic zone of the aortic arch, was studied. Investigations covered some aspects of energy metabolism and the level of the norepinephrine mediator in the muscle of the heart and also the functional state of the latter. Aethimizol was found to prevent shifts of the studied metabolic factors, induced by electric stimulation, and also to avert depletion of norepinephrine in the tissue of the myocardium and normalize its function.

In an experimental study on isolated isovolumetric guinea-pig hearts, a 2.2-fold reduction of the coronary duct combined with metabolic block caused by dinitrophenol (0.05 mM) resulted in an eleven-fold drop in the attained pressure, and a shorter electric systole, a smaller P wave, and an ST displacement on the ECG. Deep suppression of mechanical and electric activity was combined with reduced glycogen content, and greater K+ and Na+ withdrawal from the heart. Quantitatively, the drop in contractility correlated with K+ withdrawal and ST displacement. A sudden increase in coronary perfusion rate was accompanied by a rapid increase in the rate of K+ elimination from the heart which was proportionate to the rate of hyperfusion, with a simultaneous transitory rise in attained pressure, a great increment in diastolic pressure and the emergence of arrhythmia and fibrillation, the severity of the changes correlating with the degree of K+ loss. A moderate increase in K+ concentration of the perfusate prevented the development of fibrillation and drastically reduced the degree of contracture and glycogen drop during hyperfusion. The obtained results suggest that moderate accumulation of extracellular K+ during the early phase of energy generation disorder can be of a protective nature, as it contributes to a sharp reduction in contractility and energy spending to improve cell survivability in critical conditions.

The effect of cellular creatine (Cr) and adenine nucleotides (AdN) deficiency on cardiac work, ATP turnover rate and flux through creatine kinase (CK) has been investigated. Depletion of 60-65% of total heart AdN by 2-deoxyglucose treatment in the presence of pyruvate and subsequent washout resulted in only 25% decrease in contractile activity and phosphocreatine level. Substitution of 80-90% of heart Cr (and PCr) by guanidinopropionic acid (GP) by feeding of rats with 1% GP diet reduced maximal values of cardiac work, ATP turnover and flux through CK by 40-50% and elevated end diastolic pressure and index of diastolic stiffness. Hearts depleted of AdN or glycogen showed better post-ischemic recovery of mechanical function that can be attributed to restriction of accumulation of ischemic catabolytes (lactate, H+, Pi). These data imply that in myocardium PCr is an essential high energy phosphate and contractile function stays unchanged at significantly reduced ATP levels.

In 59 sexually mature male chinchilla rabbits, and in control sham-operated animals, there were compared the indicators characterizing the functional state of the heart and the levels of catecholamines and of SH groups in experimental myocardial infarction induced by ligating the descending branch of the left coronary artery. Phasic shifts were found in the heart adrenergic regulation, dependent on the stage of infarction. In all animals in the acute stage of myocardial infarction the activity of the sympatho-adrenal system was enhanced. In an extensive transmural infarction and in cases with a lethal outcome the levels of total and protein-bound noradrenaline were lowered. The course and prognosis of experimental myocardial infarction were dependent on the degree of disturbance of formation of complexes of noradrenaline with adrenoreceptor structures, caused by decreases in the levels of noradrenaline and sulphydryl groups.

Excessive stimulation of reflexogenic zone of rabbit aortic arch resulted in impairments of noradrenaline tissue reserves in heart muscle. Administration of one of the precursors of noradrenaline l-DOPA not only prevented the decrease in tissue noradrenaline content in myocardium, but restored completely its reserves, exhausted by electrostimulation of the aortic arch.

A total of 92 patients with chronic tonsilitis and cardiovascular changes were subjected to clinical observations, ECG analysis, potassium and nitroglycerine tests, and studies of the lactic acid level and creatinekinase activity as indces of myocardial metabolism. The examinations were conducted prior to and following tonsillectomy. In a majority of patients a correlation was revealed between the degree of ECG changes and the serum lactic acid level, as well as between the ECG improvement and a reduction of the lactic acid level following tonsillectomy. Three stages of tonsillogenic myocardiodystrophy were distinguished. The obtained data indicate the rationale of the used tests for the evaluation of the myocardial meabolism alterations and of the efficacy of treatment of chronic tonsillitis patients.

Changes in the cardiac pump function, contractility, relaxation and distensibility in progressive metabolic blockade induced with dinitrophenol, were compared in the guinea pig isolated heart. A fall in relaxation and distensibility occurred first and was more obvious than a fall in contractility or the cardiac output. The same relationships were observed in isolated hearts of rats with myocardial phosphocreatine deficiency. The fall in relaxation and distensibility seem to be the necessary sign of acute or chronic myocardial energy deficiency.

Neurogenic damage of the myocardium by electrostimulation of the aortic arch led to deficiency of tissue noradrenaline (the sympathetic nervous system mediator). Simultaneously there was a marked rise of the glucose-6-phosphate dehydrogenase activity. Preliminary administration of the RNA synthesis inhibitor--actinomycin D--fully prevented the increase of this enzyme activity in the myocardium produced by its neurogenic damage. The data obtained testified to the acceleration of induction of this enzyme in the myocardium in case of its neurogenic damage, this correlating with the change of tissue noradrenaline balance.

Left ventricular (LV) contractile function and pump function were depressed in isolated working hearts from rats treated with either guanidinopropionic acid (GPA), an inhibitor of creatine influx, or the anthracycline antibiotic, adriamycin, for 6 and 10 weeks, respectively. In both groups of treated animals myocardial phosphocreatine content was lower than in control hearts, while ATP content was unchanged. Hearts of treated animals exhibited only a minor depression of cardiac output with a submaximal pressure load or during volume overload. However, at maximal pressure load GPA- and adriamycin-treated hearts performed 43% and 37% less pressure-volume work than control hearts. These changes were due both to decreased LV pressure development and diminished cardiac output. LV diastolic stiffness was significantly higher at the submaximal pressure load and the LV filling pressure area, which reflected LV filling, was lower in hearts of both treated groups. The differences in both indices were exaggerated when the maximal pressure load was applied. Limited LV filling due to incomplete myocardial relaxation appeared to represent the underlying cause of cardiac failure when afterload was increased. These results may be explained if adaptation of cardiac contractile function in some chronic cardiac diseases arises from a limited energy supply to the myofibrils.

A comparison was conducted between the contractile function of the heart of hares and rabbits at rest and under isometric contractions regimens, and under such conditions the concentration of ATP and its breakdown products was studied in the myocardium of both species. It was demonstrated that the cardiac muscle of hares adapted by the evolution to the performance of intensive work does not possess any increased ability of developing systolic tensions, or any increased power of the ATP resynthesis apparatus. The advantage of such a heart-- its ability to pump an increased blood volume -- must be ensured by some different mechanism that requires still further investigations.

Experiments on the isolated hearts of guinea pigs have shown that administration of dinitrophenol in the concentrations of 0.01-0.10 mmol elicited, depending on the dose given, a decrease in pressure of a latex balloon, placed into the cavity of the left ventricle and an increase in the displacement of the SI segment on the ECG, recorded from the subendocardial layer of the apex. It is established that the rate of the coronary flow, limiting washing out of K+ and other metabolites determines the degree of depression of the contractile function with energy formation disorders and also its restoration during reoxygenation.

A 3-hour electrostimulation of the aortic arch in rabbits was followed by the exhastion of the tissue noradrenaline stores in the myocardium accompanied by increase in the activity of the glycolysis enzymes and of the enzyme limiting the process of the pentosophosphate route-G-6-PDH. The use of noradrenaline precursor - 1-DOPA restored the noradrenaline level in the myocardium completely after a 48-hour stimulation. Simultaneously there were noted no changes in the activity of the enzymes under study caused by the stimulation of the aortic arch. The data obtained confirmed the important role of the sympathetic nervous system and of its mediator - noradrenaline in the mechanism of the tissue metabolism regulation, whose derangement played a significant role in the development of dystrophic lesions of the heart tissue.

The activity of the glycolytic enzymes and of the glucose-6-phosphate dehydrogenase (G-6-PDH) were compared with the content of noradrenaline in rat myocardium and the liver after the intraperitoneal injection of high doses of noradrenaline. It was shown that 24 hours after int noradrenaline injection which caused exhaustion of endogenous catecholamine supply, the lactate content and the activities of lactic dehydrogenase were increased in the myocardium; the activity of hexokinase and G-6-PDH in rat myocardium and the liver were also increased, whereas the glucokinase activity was decreased. In these experiments alterations of the enzyme activities were shown to be similar to the alterations in the dystrophic tissues in which the catecholamine content was sharply decreased. The role of the sympathetic nervous system and its mediators in the mechanism of the enzyme regulation of the energy metabolism in the myocardium and the liver is discussed.

Administration of toxic doses of noradrenaline into rats led to exhaustion of noradrenaline reserves in liver and heart tissues with the simultaneous increase in the activity of glucose-6-phosphate dehydrogenase in the tissues. Actinomycin D, administered together with noradrenaline, completely prevented the elevation of the G6PD activity in the tissues studied. The data obtained suggest that sympathetic nervous system and its mediator are responsible for regulation of the rate of enzymatic protein synthesis in tissues.