Noninvasive and Invasive Study of the Pumping Function of Rat Heart in Myocardial Infarction.

The cardiohemodynamics was studied 2 and 4 weeks after myocardial infarction modeling in Wistar rats. We compared the data obtained by echocardiography (echoCG) and catheterization of the left ventricle. The myocardial infarction was modeled by ligation of the left anterior descending coronary artery. EchoCG and the left ventricle catheterization were performed before and after myocardial infarction modeling. Similar results were obtained by both methods, namely the left ventricle dilatation, bradycardia, a reduced ejection fraction and delayed relaxation. According to echoCG, the end-diastolic left ventricle volume increased by 2 times, and initial diastolic left ventricle volume - by more than 5 times. The left ventricle catheterization showed lower rise, by 32 and 69%, respectively. The overestimated volume of the left ventricle in myocardial infarction according to echoCG data in comparison with catheterization can be explained by changes in the geometry of the ventricle (bulging of a part of the ventricular wall).

The Role of Arterial Elasticity in Determining the Degree of Chronic Heart Failure in Myocardial Infarction.

Aim      To study the left ventricular (LV) contractile and pumping function during the recovery phase following ligation of the anterior descending coronary artery (CA).Material and methods  Cardiodynamic parameters were studied in Wistar rats 2-4 weeks after experimental myocardial infarction (MI). MI was induced by ligation of the anterior descending CA under zoletil anesthesia. LV catheterization was performed with a standard FTH-1912B-8018 PV catheter inserted into the LV through the right carotid artery.Results After the induction of MI, the mortality rate of animals was 50%. Survived animals developed significant LV dilatation and a decrease in ejection fraction (EF) by an average of 31%. However, major indexes of the pumping function, including minute volume, heart work, and maximum ejection velocity, were within a normal range whereas the maximum filling velocity was almost doubled. Approximately 50% of hearts with dilated LV had normal EF, delayed relaxation, and increased LV diastolic pressure, which qualified this group as a diastolic dysfunction group. The systolic dysfunction group with EF less than 50% of normal had similar values of myocardial contractility and relaxation but differed from the diastolic dysfunction group in more than 50% reduced maximum LV ejection velocity and 1.7 times increased elasticity of the arterial wall. A close inverse correlation was found between these values (r= -0.91).Conclusion      The study results showed that, with a similar myocardial contractile function, the cardiac pumping function is determined by the elasticity of the aortic wall. Therefore, restriction of reactive fibrosis during MI is an important task of modern cardiology.

HEMODYNAMICS AND CARDIAC CONTRACTILE FUNCTION IN TYPE 1 DIABETES.

The cardiohemodynamics was studied 1 week after the administration of streptozotocin (60 mg / kg) or 2 weeks after a dose of 30 mg / kg. All rats had a significantly elevated level of glucose in the blood (up to 27-31 mM). In an echocardiographic study, about 1/3 of diabetic animals exhibited systolic dysfunction, and the remaining 2/3 - diastolic dysfunction with an increase in isovolumic relaxation time by 1.5 times. The catheterization of the left ventricle (LV) with a sensor that allows simultaneous measuring LV pressure and volume in both groups revealed decreased cardiac output by 25-31% and maximal ejection rate by 34-50%. However, LV developed pressure, the maximal rate of its development and the level of blood pressure remained within the control values, thus reduced LV ejection rate was probably due to increased arterial stiffness - a negative correlation was found between these indicators (r = - 0.70). The diastolic dysfunction group differed from systolic dysfunction by a significantly smaller end diastolic volume by 22%. Thus, in type 1 diabetes, LV remodeling with reduced end diastolic volume allows to maintain a normal ejection fraction in the presence of distinct heart failure.

Systolic Dysfunction of the Heart in Type 1 Diabetes Mellitus.

Impaired insulin synthesis is accompanied by hyperglycemia and the development of diabetic cardiomyopathy. Echocardiography and left-ventricular catheterization were employed for studying the contractile function of the left ventricle in 2 weeks after administration of streptozotocin (60 mg/kg). The results obtained by both methods were similar and indicated the development of systolic dysfunction with a 27% decrease in cardiac output. The invasive study showed that the maximum rate of left-ventricular pressure development, the contractility index, and systolic left-ventricular pressure were within the normal range, but the peak ejection rate was reduced by 28%. BP was normal, but the vascular stiffness index was increased by about 1.5 times and inversely correlated with the peak ejection rate (r=-0.69). The results showed that systolic dysfunction in type 1 diabetes model was due to reduced ejection from the left ventricle at normal rate of left-ventricular pressure development.

[Prevention of Diastolic Dysfunction Caused by Doxorubicin by Mitochondrial Antioxidant Plastomitin].

Aim      An attempt to prevent the development of diastolic dysfunction (DD) with the mitochondrial antioxidant plastomitin on a model of doxorubicin-induced cardiomyopathy. DD is a type of chronic heart failure. Due to the increasing number of patients with this condition and the absence of effective therapy, development of means for DD correction is a relevant objective.Material and methods  Cardiomyopathy was modeled in 17 rats by two subcutaneous injections of doxorubicin 2 mg/kg/week. The other group (n=17), also administered with doxorubicin, received plastomicin 0.32 mg/kg daily subcutaneously. Left ventricular function was evaluated with echocardiography (EchoCG) and cardiac catheterization with simultaneous pressure and volume monitoring.Results According to EchoCG data the ejection fraction remained unchanged in the experimental groups. Cardiac catheterization showed disorders of both myocardial contractility and relaxability only in the doxorubicin group.Conclusion      A course of plastomitin in combination with the doxorubicin treatment can maintain normal heart contractility and thereby, prevent the known doxorubicin cardiotoxicity.

[Early changes of energy metabolism, isoformic content and level of titin phosphorylation at diastolic dysfunction].

RELEVANCE:  Diastolic dysfunction occurring at hypertension, obesity, diabetes, or treatment with doxorubicin tends to prevail in all patterns of chronic heart failure. Lack of effective therapy forces to look more into the metabolic processes in cardiomyocytes. OBJECTIVE:  Assess energy metabolism in cardiomyocytes and changes in titin, a giant myofibril protein that responsible for their elasticity. MATERIAL AND METHODS:  The study model was cardiomyopathy occurring after the 4-week administration of doxorubicin (2 mg/kg weekly). Diastolic dysfunction was identified by echocardiography and catheterization with the simultaneous measurement of pressure and volume of the left ventricle (LV). RESULTS:  The levels of adenine nucleotides and phosphocreatine in the heart of animals treated with doxorubicin differed little from the normal values, but lactate levels were increased manifold. A 50% increase in the level of titin phosphorylation was detected, which correlated (r = 0,94) with a nearly twofold increase in the share of a more elastic N2BA-isoform of this protein. CONCLUSION: This form of diastolic dysfunction involves the activation of anaerobic metabolism and increased stretching of myofibrils facilitating LV filling.

[Mitochondrial Antioxidant Plastomitin Improves Cardiac Function in Doxorubicin-Induced Cardiomyopathy].

The aim of the study was to ascertain whether the use of plastomitin, the mitochondrial antioxidant, can affect the development of systolic dysfunction that occurs in rats after 4 weeks of doxorubicin treatment (2 mg/kg weekly). Materials and methods. Male Wistar rats weighing 320-380 g were used in this work. Echocardiographic study was carried out using Vevo 1100 with linear probe 13-24 MHz frequency. Results. Echocardiographic study of rats through 8 weeks from the beginning of doxorubicin treatment showed the presence of systolic dysfunction with decrease of ejection fraction of the left ventricle (LV) by 32%. Hearts of rats, to which plastomitin (0.32 mg/kg daily) was administered simultaneously with doxorubicin, showed significantly increased ejection fraction and shortening fraction as compared with doxorubicin group, and these values were close to the control. In experiments with simultaneous registration of LV pressure and volume, it was found that the hearts of all rats treated with doxorubicin showed reduced contractility index and stroke work, while maintaining normal cardiac output. Such compensation in experiments with treatment with doxorubicin alone was achieved through significant reduction in the peripheral resistance, slowing of myocardial relaxation, and facilitation of LV diastolic filling during prolonged diastolic pause (the heart rate was slowed by 23%). In experiments with simultaneous application of doxorubicin and plastomitin, the compensation was achieved through preservation of myocardial contractility and relaxability, the heart rate and peripheral resistance. This method of compensation is more beneficial for the body, because it does not restrict the supply of organs and tissues with oxygen, and has significant advantage over doxorubicin group at equal heart rate. Conclusion. The results allow to conclude that the use of plastomitin together with doxorubicin prevents the development of doxorubicin-induced systolic dysfunction.

[Pressure and Volume Characteristics of the Left Ventriclе in Its Diastolic and Systolic Dysfunction].

The Aim of the study was a detailed investigation of pressure volume-loop (PV-loop) curves in the rat heart during development of doxorubicin cardiomyopathy. MATERIALS AND METHODS: Cardiomyopathy in rats has been developed after 4 weeks doxorubicin administration (2 mg / kg weekly). RESULTS: Echocardiographic study of rats in 8 weeks from onset of doxorubicin administration showed preponderance of systolic dysfunction (67 %) with decrease of left ventricular (LV) ejection fraction (EF) by 30 %. Simultaneous registration of LV pressure and volume showed that diastolic LV volume was preserved in doxorubicin-treated rats due to considerable lengthening of the diastole, the heart rate was reduced by 22 %. These hearts also showed slowing of relaxation, reduced maximal rate of pressure development and stroke work, as well as significant reduction in peripheral arterial resistance. Diastolic dysfunction differed from the systolic one by normal systolic EF and preserved LV contractility index as well as lower diastolic LV pressure throughout the diastole. CONCLUSIONS: Based on these data, four compensatory mechanisms associated with cardiomyopathy were distinguished - 1) slowing of myocardial relaxation, prolonging myofibrillar active state, 2) reduction of peripheral arterial resistance for easier LV ejection, 3) heart rate reduction, prolonging diastolic pause and thus facilitating better LV filling and 4) increased pressure in the small circle, also contributing to the LV rapid filling.

[Metilin Improves Сardiac Function in Rabbits With Chronic Heart Failure].

AIM: To study effects of intravenous infusion of a cardioprotective drug metilin, developed at the "National Medical Research Center of Cardiology" on indices of cardiac function in rabbits in vivo after prolonged administration of doxorubicin. MATERIALS AND METHODS: Animals of the experimental group were intravenously injected with doxorubicin (2 mg / kg once a week) for 8 weeks, animals of the control group received the same volume of saline. Myocardial damage was characterized by an increase in concentration of malondialdehyde (MDA), troponin (TnI) and MB-fraction of creatine kinase (CK-MB) in venous blood and by disturbances in the left ventricle (LV) structure at morphological examination. Metilin effects on cardiac function were assessed by echocardiography and LV catheterization by the Millar catheter tip pressure transducer. RESULTS: Doxorubicin administration led to a decrease of the body mass of animals, an increase of the plasma concentration of cardiac markers CK-MB and TnI, lipid peroxidation (LPO) product MDA in venous blood, and pronounced disturbances in the structure of LV fibers and microvessels. At the same time, a significant decrease of myocardial contractility indices was observed. Manifestations of this decrease were increase of the end-diastolic and end-systolic dimensions (EDD and ESD, respectively), and decreases in the shortening fraction and ejection fraction (SF and EF, respectively) compared to baseline values. These changes indicated development of chronic heart failure (CHF) in animals of the experimental group. Against this background, intravenous infusion of metilin significantly increased SF and EF, but did not affect the heart rate. Beneficial effects of metilin on the indices of cardiac contractility and relaxation were maintained after the infusion was stopped. Noteworthy, metilin exerted greater influence on cardiac function of rabbits with CHF compared to control animals that did not receive doxorubicin. CONCLUSION: The obtained results indicate the potential of metilin to reduce LV dysfunction during chemotherapy with doxorubicin.