[Complex study of the rat heart at isoproterenol damage].

Introduction of isoproterenol (an agonist of beta-adrenoreceptors) to rats is one of the widespread experimental models of cardiac failure. It is caused by damage of cardiomyocytes with the subsequent development of substitutive fibrosis. The purpose of the given work was the complex characteristic of cardiac function by means of invasive and noninvasive (echocardiography and impedansometry) methods of research. Isoproterenol was injected twice with a daily interval in dozes 85, 120, 150 or 180 mg/kg. Echocardiographic study of the heart in 2 weeks revealed obvious attributes of cardiac failure (left ventricular dilatation, lowered ejection fraction) in the groups which have received high cumulative dozes of isoproterenol (300-360 mg/kg). The catheterization of the left ventricle in these groups has shown raised enddiastolic pressure, decreased maximal rate of pressure development and fall, and also lowered indices of myocardial contractility and relaxability. In the groups which have received smaller isoproterenol dozes, apparent decrease in relaxability parameters (constants of isovolumic and auxovolumic relaxation) has been revealed at only slightly changed parameters of contractility. A strong correlation between echocardiographic and invasive parameters of myocardial contractility has been found. The phase analysis of the cardiac cycle has shown a lengthening of isometric phases of contraction and relaxation, as well as duration of ejection due to shortening duration of filling of both ventricles. Cardiomyocytes isolated from hearts with obvious cardiac failure responded to electrostimulation by arrhythmic contractions and also by much slowed and incomplete removal of free Ca++ from the myoplasm. Results allow to conclude that relatively smaller extent of myocardial damage is accompanied by decreased relaxability at slightly changed contractility, while at greater degree of damage both processes fail, but delay of relaxation still prevails.

[The study of hypotensive action of dinitrosyl-iron complex with glutathione containing drug oxacom in healthy volunteers].

On the basis of earlier executed studies of hypotensive effect of dinitrosyl iron complexes (DNIC) with glutathione, the drug has been created in industrial conditions named oxacom. Preliminary pharmacological studies of oxacom have not revealed negative qualities. The drug has been now tested in 14 healthy men in whom at single intravenous introduction it caused typical response - a decrease of diastolic as well as systolic arterial pressure on 24-27 mmHg through 3-4 min with subsequent very slow restoration in 8-10 hours. The heart rate after initial rise was quickly normalized. Echocardiography revealed unaltered cardiac output in spite of reduced cardiac filling by 28%. The multilateral analysis of clinical and biochemical data has revealed an absence of essential alterations which could lead to pathological consequences. The drug is recommended for carrying out of the second phase of clinical trial. The comparative study of the efficiency of hypotensive action of oxacom, S-nitrosoglutathione (GS-NO) and sodium nitrite (NO2) in rats has shown that the duration of effect was the greatest at oxacom action.

[Modifications to the solution for reperfusion of the ischemic heart]. / Modifikatsii rastvora dlia reperfuzii ishemizirovannogo serdtsa.

Isolated working guinea pig hearts were subjected to 30-min total normothermic ischemia and 30-min reperfusion with modified Krebs solution to which various agents were added. The presence of glutamate in the solution resulted in better recovery of cardiac pump function and higher myocardial energy phosphate levels. Addition of phrelone, a calmodulin inhibitor, or adenosine and ribose did not improve pump function. The similar functional recovery was observed after addition of taurine instead of glutamate and their combination exerted even higher functional recovery while further addition of phosphocreatine was not so effective.

[High specificity in the molecular mechanism of the protective action of phosphocreatine on the myocardium in ischemia]. / Vysokaia spetsifichnost' molekuliarnogo mekhanizma zashchitnogo deistviia fosfokreatina na miokard pri ishemii.

To study the character of the mechanism of protective action of phosphocreatine on ischemic myocardium the effects of phosphocreatine (PCr) and phosphoarginine (PArg) were compared. PCr and PArg were shown to expose identical Ca2+-chelating properties and were used as their Na-salts. Only PCr protected the cardia function during ischemia and simultaneously inhibited the accumulation of lysophosphoglycerides, products of phospholipid degradation. PArg failed to exert both of these effects. By an EPR probe method PCr was shown to increase the order of structural organization of phospholipids in the cardiac sarcolemmal vesicles. The results show that the effect of PCr on ischemic myocardium is not due to nonspecific changes in the ion composition of a solution, but most probably due to highly specific effect of phosphocreatine on the phospholipid membrane of the cardiac cells sarcolemma.

[Contractile function of the isolated heart in chronic adriamycin-induced myocardial lesions]. / Sokratitel'naia funktsiía izolirovannogo serdtsa pri khronicheskom porazhenii miokarda adriamitsinom.

Adriamycin, administered to rats for 4 weeks, caused insufficiency of isolated heart contractility with a twofold reduction of cardiac output in surviving animals. The same cumulative dose of adriamycin, administered to rats over 10 weeks, was not associated with any significant reduction of the heart's pumping function. However, heart rate increase by atrial electrostimulation that shortened the diastolic pause to a control level, also reduced the minute and stroke volumes by 38%, as compared to the controls. All animals showed increased diastolic stiffness of the left ventricle that must have interfered with its filling, particularly so in case of low inflow pressure, and disturbed atrial automaticity, as reflected in bradicardia in rats and supraventricular arrhythmia in guinea pigs.

[Study of the protective effect of phosphocreatine on the ischemic myocardium during cardioplegia using the P-31 NMR method]. / Issledovanie metodom 31P-IaMR zashchitnogo deistviia fosfokreatina na ishemizirovannyi miokard v usloviiakh kardioplegii.

Using 31P-NMR technique it was shown that exogenous phosphocreatine (10 mM) added in the cardioplegic solution provided higher levels of recovery of intracellular ATP (approx. 60% vs. 26% in the control) and phosphocreatine (90% vs. 43%) in perfused rat hearts after 35 min of total ischemia. Simultaneously significantly higher levels of contractile recovery (90% vs. 35%) and a three-fold decrease in creatine kinase release into the perfusate were observed. These effects of exogenous phosphocreatine can be related to either intracellular action of this compound or its interaction with cellular membrane.

[Relationship between the frequency and amplitude of myocardial contractions in rats adapted to heat]. / Zavisimost' mezhdu chastotoi i amplitudoi sokrashchenii serdechnoi myshtsy u adaptirovannykh k teplu krys.

Papillary muscles from the left ventricle of rats contracted under the effect of electrostimulation with the frequency of 0.2 c. p. s. in Krebs' solution at 28 degrees C. A study was made of the contraction amplitude with the increased stimulation frequency. Following preliminary heat adaptation (3 hours a day at 35 degrees C for one month) the contraction amplitude of the myocardium of the adapted animals with a high frequency was greater than the control level. This difference persisted at 36 degrees C and disappeared at 25 degrees C. Apparently adaptation leaves a definite structural trace in the cells of the cardiac muscle.