In Vivo Reduction of Reperfusion Injury to the Heart with Apelin-12 Peptide in Rats

Abstract

Apelin-12 (A-12) peptide was synthesized by automated solid phase method and purified by reverse phase HPLC. Its homogeneity and structure were confirmed by HPLC, (1)H-NMR spectroscopy, and mass spectroscopy. Acute myocardial infarction was induced by 40-min occlusion of the left coronary artery with subsequent 60-min reperfusion in narcotized Wistar rats. Peptide A-12 was injected (intravenous bolus, 0.07 or 0.35 μmol/kg) to experimental animals simultaneously with the beginning of reperfusion. Injections of A-12 in these doses led to reduction of systolic BP to 67 and 85% of the initial level, respectively, which was virtually restored completely by the end of reperfusion, and to a significant reduction of the infarction focus in the myocardium (by 21 and 34% in comparison with the control, respectively). Injection of A-12 in a dose of 0.35 μmol/kg led to reduction of plasma concentrations of necrosis markers in comparison with the control by the end of reperfusion: MB-creatine kinase by 56%, lactate dehydrogenase by 30%. The results attest to vasodilatory effects of A-12 under conditions of heart reperfusion in vivo; the peptide injected after local ischemia limits the myocardial infarction size and reduces damage to cardiomyocyte membrane.

Apelin could reduce risk of contrast-induced nephropathy in patients with congestive heart failure

“…The antioxidant activity of apelin-13 were verified by decrease of malondialdehyde (MDA) and ROS formation with a concurrent increase in superoxide dismutase activity in several experimental studies [14,[29][30][31][32].…”

The role of inhibition of NO formation in the metabolic recovery of ischemic rat heart by apelin-12

“…In order to test correctness of our hypothesis we have synthesized apelin 12 identical to C terminal fragment of animal and human apelin. Using isolated perfused rat heart in situ we demon strated that administration of A 12 improved func tional and metabolic recovery of reperfused heart and restricted sizes of myocardial infarction [12,13].…”

“…Decreased cardiomyocyte death and closure of mitochondrial permeability transition pore induced by apelin 13 and apelin 12 [3,4,13] suggests the effects of these peptides on energy metabolism of ischemic myocardium and increased expression of eNOS may be one of key mechanism of this effect [4,14]. However, there are just a few reports on the effect of apelin 13 on eNOS expression and NO formation in ischemic myocardium and results are rather contra dictory [3,4].…”

The protective effect of apelin on ischemia/reperfusion injury

“…As we know, I/R injury could induce myocardial infarction [31]. Under conditions of heart reperfusion in vivo, apelin-12 induced vasodilatory effects, and apelin-12 injected after local ischemia limited the myocardial infarction size and reduced damage to cardiomyocyte membrane [23]. The action of apelin-12 in myocardial protection against I/R damage involved NO-dependent mechanisms [22].…”