Cardioprotective efficiency of pharmacological postconditioning using lactic acid in ischemia-reperfusion of the myocardium in rats with transitional hypercholesterolemia

Cardiovascular disease is the leading cause of death all over the world: for no other reason as many people die every year as from the cardiovascular disease. Taking into account the high medical and social significance of the problem of treating patients with coronary heart disease and acute myocardial infarction, the search for new effective methods of preventing or weakening ischemic myocardial damage and revealing the mechanisms of their implementation is an urgent task of modern experimental and clinical medicine. The aim of the study was to experimentally test the cardioprotective efficiency of pharmacological postconditioning with lactic acid in myocardial ischemia-reperfusion in rats with transient hypercholesterolemia.In the course of the study, it was found that remote ischemic postconditioning (RIPostC) during myocardial ischemia-reperfusion leads to an increase in the level of lactate in the blood and has an infarction-limiting effect in rats. It was revealed that lactate, after injection into the bloodstream of animals at a dose of 10 mg/kg 25 minutes after the start of reperfusion, like RIPostC, leads to a decrease in the necrosis area in the left ventricular of the myocardium. Pharmacological postconditioning with lactate is ineffective in the limiting necrosis area in the myocardium of the left ventricle of rats with transient hypercholesterolemia. The presence of such a risk factor for cardiovascular diseases as hypercholesterolemia can serve as a criterion for excluding the use of pharmacological postconditioning with lactate as a way to reduce ischemic and reperfusion damage to the myocardium in patients with acute myocardial infarction.

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.

CpG postconditioning after reperfused myocardial infarction is associated with modulated inflammation, less apoptosis, and better left ventricular function

Cytosine-phosphate-guanine (CpG) postconditioning seems to mediate inflammation via Toll-like receptor-1 and Toll-like receptor-9 signaling. Enhanced cytokine and chemokine expressions are partly attenuated by IL-10 and matrix metalloproteinase-8 (MMP8) induction, being associated with lower macrophage infiltration and M1-monocyte differentiation. Furthermore, switch from α- to β-MHC and balanced MMP/TIMP expression led to lesser cardiomyocyte apoptosis, smaller scar size, and preserved cardiac function. Data of pharmacological postconditioning have been widely disappointing to date. Our study suggests a new pathway promoting myocardial postconditioning via Toll-like receptor activation.

Effects of resveratrol postconditioning on cerebral ischemia in mice: role of the sirtuin-1 pathway

Evidence has demonstrated that resveratrol preconditioning exhibits neuroprotection against cerebral ischemia–reperfusion (IR) injury. The current investigation aimed to explore whether pharmacological postconditioning, by administering resveratrol, after a sustained ischemia and prior to prolonged reperfusion abrogates cerebral IR injury. Cerebral IR-induced injury mice model was employed in this study to evaluate the neuroprotective effects of pharmacological postconditioning with resveratrol (30 mg/kg; i.p.) administered 5 min before reperfusion. We administered sirtinol, a SIRT1/2 selective inhibitor (10 mg/kg; i.p.) 10 min before ischemia (17 min) and reperfusion (24 h), to elucidate whether the neuroprotection with resveratrol postconditioning depends on SIRT1 activation. Various biochemical and behavioural parameters and histopathological changes were assessed to examine the effect of pharmacological postconditioning. Infarct size is estimated using TTC staining. It was established that resveratrol postconditioning abrogated the deleterious effects of IR injury expressed with regard to biochemical parameters of oxidative stress (TBARS, SOD, GSH), acetylcholinesterase activity, behavioural parameters (memory, motor coordination), infarct size, and histopathological changes. Sirtinol significantly reversed the effect of resveratrol postconditioning. We conclude that induced neuroprotective benefits of resveratrol postconditioning may be the consequence of SIRT1 activation and resveratrol can be considered, for further studies, as potential agent inducing pharmacological postconditioning in clinical situations.