[The Action of Apelin-12 and Its Analog on Hemodynamics and Cardiac Contractile Function of Rats With Isoproterenol-Induced Myocardial Lesion].

Introduction of isoproterenol (beta-adrenoreceptor agonist) into rats is one of the widespread experimental models of heart failure. It is caused by diffuse ischemic damage of cardiomyocytes, followed by development of substitutive fibrosis. Apelin is a natural regulator of the myocardial contractility. The effects of apelin molecule fragment, apelin-12 and its more stable synthetic analogue, apelin-12-2 on cardiac contractile function of rats with isoproterenol-induced myocardial lesion (IML) and control animals has been studied in this work using invasive (catheterization of the left ventricle) and non-invasive (echocardiography and impedansometry) methods. Infusion of both peptides was made by sequentially increasing rate from 0.5 to 50 µg/kg/min. In the control group, efficacy of apelin-12 was low while apelin-12-2 moderately but significantly increased indices of myocardial contractility and relaxability. These changes were more pronounced in rats with IML and, in addition, the heart rate and LV systolic pressure increased in this group. These results correlate well with echocardiographic studies which showed increases of LV end diastolic volume, stroke volume and ejection fraction by 17-38%. These alterations are probably due to improved Ca2+ transport in cardiomyocytes, as in experiments on isolated cardiomyocytes both apelins have facilitated and improved Ca2+ removal from myoplasma. The results allow to conclude that apelin-12-2 seems to be a promising candidate for further development as a therapeutic agent in heart failure.

[Biomarkers in Heart Failure: Apelin Level Is Not Associated With Presence and Severity of the Disease].

We tested possibility of the use of apelin-12 as a biomarker of chronic heart failure (CHF). The study comprised 108 patients with I-IV functional class CHF of various etiology (ischemic heart disease, dilation cardiomyopathy) and 40 healthy volunteers. Blood samples were taken at hospital admission before prescription of pharmacological therapy. In all patients we carried out echocardiography with calculation of end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (EF). Blood plasma apelin-12 concentration was compared with CHF market NT-proBNP. Mean apelin-12 concentrations were 0.86 ± 0.22 hg/ml in healthy volunteers and 0.8±0.35, 0.81 ± 0.29, 0.68 ± 0.38, 0.82 ± 0.35 hg/ml in patients with CHF classes I, III, III, IV, respectively. There was no significant differences between appelin-12 concentrations in various classes of CHF. No correlations were found between apelin-12 and EF, EDV, ESV, sex, age, smoking, body mass index, and NT-proBNP level. Concentration of NT pro-BNP level correlated with CHF severity. Thus apelin-12 did not show itself as reliable biomarker of CHF.

[Biomarkers in Heart Failure: Apelin Level Is not Associated With Presence and Severity of the Disease].

We tested possibility of the use of apelin-12 as a biomarker of chronic heart failure (CHF). The study comprised 108 patients with I-IV functional class CHF of various etiology (ischemic heart disease, dilation cardiomyopathy) and 40 healthy volunteers. Blood samples were taken at hospital admission before prescription of pharmacological therapy. In all patients we carried out echocardiography with calculation of end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (EF). Blood plasma apelin-12 concentration was compared with CHF market NT-proBNP. Mean apelin-12 concentrations were 0.86+/-0.22 hg/ml in healthy volunteers and 0.8+/-0.35, 0.81+/-0.29, 0.68+/-0.38, 0.82+/-0.35 hg/ml in patients with CHF classes I, II, III, IV, respectively. There was no significant differences between appelin-12 concentrations in various classes of CHF. No correlations were found between apelin-12 and EF, EDV, ESV, sex, age, smoking, body mass index, and NT-proBNP level. Concentration of NT pro-BNP level correlated with CHF severity. Thus apelin-12 did not show itself as reliable biomarker of CHF.

[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.

[Galectin 3--a new biomarker for diagnostics and outcome of chronic heart failure].

Galectins--lectins binding ß-galactosides their properties and biological role have been described. Galectines family in mammalians consists of 15 members. Galectin-3 is atypical specimen of galectins family. Its participation in fibrosis, cardiac remodeling, immune and inflammation responses have been shown. Employment galectin-3 as new independent biomarker for diagnosis of acute heart failure and outcome predictor in patients with chronic heart failure (HF) are discussed. Diagnostic and prognostic values of galectin-3 are compared with famous and wide using HF marker NT-proBNP. Combined employing biomarkers for diagnostic and prognostic purpose of HF have been discussed. Using galectin-3 as therapeutic target in treatment of chronic HF in future is suggested.

[Modification of the FF neuropeptide enhances its hypertensive effect].

Neuropeptide FF (H-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) injected intravenously temporarily enhanced the arterial pressure (AP) and the heart rate (HR). However, its role in the regulation of blood circulation is obscure. To study the properties of the molecule, its analogue was synthesized, in which proline in position 7 was substituted with glycine, and leucine in the position 2 with norleucine. Modified neuropeptide FF (FFm) also temporarily and in a dose-dependent manner increased the AP and HR; however, the equal degree of increase was reached at doses of FFm being 5-7 times lesser as compared with the natural peptide. The application of the FFm at hemorrhagic shock excluded mortality of animals during the experiment, considerably increased the degree of AP and HR restoration in the remaining experiments, and improved the survival of animals in 24 hours. It has been found that the level of antibodies to the fragment of hFF1 receptor in the serum is lower in spontaneously hypertensive rats SHR as compared with Wistar rats, but it is increased in patients of cardiological profile as compared with donors. The findings suggest involvement of neuropeptide FF in the regulation of blood circulation; however, the precise mechanisms remain to be determined.