The influence of old age on cardioprotective efficiency of pharmacological postconditioning using lactic acid in ischemia-reperfusion of the myocardium in experiment

Not only the prevalence, but also the death rate from the coronary heart disease, including myocardial infarction, is higher in older people than among young people. A demographic shift towards an aging population will lead to a further increase in the prevalence of cardiovascular diseases among the elderly population. Therefore, one of the urgent aims of modern experimental and clinical medicine is to develop methods aimed at limiting reversible and irreversible damage to the myocardium, including in elderly patients. There are a lot of the data supporting the cardioprotective efficiency of such phenomena as ischemic and pharmacological pre- and postconditioning that reduce ischemic and reperfusion damage in young hearts. However, the information on the effectiveness of these phenomena in experiments on old animals is very scarce, contradictory, and not fully understood. The aim of the study was to experimentally evaluate the influence of old age on the reproducibility of the cardioprotective efficiency of pharmacological postconditioning using lactic acid in ischemia-reperfusion of the myocardium. In the course of the study, it was found that neutral lactate, after being administered into the blood flow of animals at a dose of 10 mg/kg 25 minutes after the onset of reperfusion, leads to a decrease in the infarct size of the left ventricle of the myocardium in old rats. Pharmacological postconditioning using lactate is not effective in reducing the duration of cardiac arrhythmias in ischemia-reperfusion of the myocardium in old rats; however, there is a tendency to reduce the incidence of reperfusion arrhythmias and the total duration of cardiac arrhythmias. The obtained data suggest that the presence of such a risk factor for cardiovascular diseases as old age is not a criterion to exclude the use of pharmacological postconditioning with lactate as a way to reduce ischemia and reperfusion injury of myocardium.

Ivabradinum supplements the clinical efficacy of percutaneous coronary intervention in patients with coronary heart disease with stable angina

The review is devoted to the role of ivabradinum in the procedure of percutaneous coronary intervention (PCI) in patients with ischemic heart disease with stable angina. It is reported that reperfusion of the myocardium with PCI, even in combination with modern drug therapy, does not have a complete clinical effect. The authors substantiate the possibility of completing the clinical effect of PCI in such patients by prescribing ivabradinum. The drug reduces the heart rate more than with medication without it.

Phenylephrine and sustained acidosis activate the neonatal rat cardiomyocyte Na+/H+ exchanger through phosphorylation of amino acids Ser770 and Ser771

The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitously expressed membrane protein that regulates intracellular pH in the myocardium. NHE1 is also important in mediating myocardial hypertrophy, and the blockage of NHE1 activity prevents hypertrophy and reduces ischemia-reperfusion injury in animal models. We recently demonstrated that extracellular-regulated kinase (ERK)-mediated activation of NHE1 occurs during ischemia-reperfusion of the myocardium. To understand the regulation of NHE1 in the myocardium by phosphorylation, we expressed a series of adenoviruses that express wild-type and mutant cDNA for NHE1. All exogenous cDNA for NHE1 had additional mutations [Leu163Phe/Gly174Ser], which increases NHE1 resistance to EMD-87580 (a specific blocker of NHE1) 100-fold, and allowed the measurement of exogenous NHE1 while inhibiting endogenous NHE1. By examining the effects of a series of mutations of the NHE1 cytosolic region, we determined that the amino acids Ser770 and Ser771 were essential for the acute activation of NHE1 activity in rat cardiomyocytes. The specific mutation of either residue prevented the rapid activation of exchanger activity by a sustained intracellular acidosis through ERK-dependent pathways. The same amino acids were critical to phenylephrine-mediated, ERK-dependent activation of NHE1 activity and increased the phosphorylation in intact rat cardiomyocytes. The results demonstrate that both sustained intracellular acidosis and phenylephrine rapidly activate the NHE1 protein in intact cardiac cells through ERK-dependent pathways that act on a common pathway mediated by amino acids Ser770 and Ser771 of the cytosolic tail of the protein.

Estrogen diminishes postischemic hydroxyl radical production

Reperfusion of blood flow to an ischemic myocardium is imperative to survival; ironically, it may also manifest several pathophysiological conditions. The most important of these are reperfusion arrhythmias and tissue injury and/or death. The mechanisms involved in reperfusion arrhythmias remain to be fully elucidated; however, increasing evidence indicates that reperfusion-induced arrhythmias are a free radical-mediated phenomenon. Acute administration of conjugated equine estrogen to dogs attenuates ischemia- and reperfusion-induced arrhythmias. The cardioprotective effect of estrogens in postmenopausal women is well documented, and recent studies suggest that estrogens possess strong antioxidant properties, with equine estrogens most potent. In this study we show that administration of conjugated equine estrogen to fully anesthetized dogs abolishes the burst of ⋅ OH radicals typically produced on reperfusion of the myocardium. This indicates that estrogen might attenuate reperfusion-induced ventricular arrhythmias by virtue of its antioxidant properties, suggesting a novel cardioprotective effect of the hormone.

Evaluation of phospholipid peroxidation as malondialdehyde during myocardial ischemia and reperfusion injury

Peroxidation of membrane phospholipid polyunsaturated fatty acids is considered a major mechanism of the damage occurring on reperfusion of the myocardium after a prolonged period of ischemia. The evidence in support of this mechanism of damage is based on tissue malondialdehyde quantitation by the thiobarbituric acid test (TBA test). In an attempt to verify this topic, we have subjected isolated and Langendorff-perfused rabbit hearts to a period of 60 min of severe ischemia plus 30 min of reperfusion. At appropriate time points, malondialdehyde was determined in the tissue by means of TBA test and directly by reversed-phase, high-pressure liquid chromatography (HPLC). We have found no correlation between the two compared assays. During reperfusion, there was the formation of non-lipid-related, malondialdehyde-like, TBA-reactive substance that leads to overestimation of the extent of lipid peroxidation. On the contrary, by direct HPLC quantitation, there was a decrease of tissue malondialdehyde during ischemia and during the early phases of reperfusion. Our results demonstrate that TBA test is not a reliable index of lipid peroxidation in organ systems.