[Prospects of clinical application of pharmacological imitation of the phenomenon of ischaemic postconditioning of the heart]. / O perspektivakh klinicheskogo primeneniia farmakologicheskoi imitatsii fenomena ishemicheskogo postkonditsionirovaniia serdtsa.

Pharmacological imitation of the phenomenon of ischaemic postconditioning of the heart appears to exert a cardioprotective effect in the reperfusion period. It was determined that the protective effect may be carried out resulting from activation of the adenosine, opioid and bradykinin receptors. However, there is yet no common point of view concerning the question as to the activation of what subtypes of the receptors the cardioprotective effect of adenosine, opioids and bradykinin is associated with. The clinical findings strongly suggest that further studies are required, since the data obtained in the hitherto carried out trials are ambiguous, scarce, and sometimes yield contradicting results. Several clinical trials of adenosine have been conducted and in the majority of cases positive results were obtained. Adenosine administered in a dropwise manner was found to exert a cardioprotective effect. However, not all researchers succeeded in demonstrating this protective effect. Only one clinical trial was carried out with the opioid receptor agonist - morphine, yielding positive results, with morphine exerting a cardioprotective effect. Feasibility of the clinical application of bradykinin as a cardioprotector is not of current relevance because of its numerous side effects.

[[Role of dyslipidemia in pathogenesis of vascular events among Arctic Circle population].

Habitation within the polar circle increases cardiovascular mortality rate and particularly increases mortality as a result of coronary events. The main reason of elevation of mortality from these diseases is a dyslipidemia which developed more among alien population residing long time in Far North. Dyslipidemia is less found among aboriginal population of Arctic Circle keeping traditional way of life and respectively it is low rate of mortality from coronary heart disease. The data showed that low rate of dyslipidemia among aboriginal population of North regions depends on fish consumption which is high content of Ω3-polyunsaturated fatty acids.

[Opioids--triggers of adaptive phenomenon of ischemic preconditioning of heart].

It was established that short-term ischemia/reperfusion evokes an increase in myocardial tissue of enkephalin levels. A blockade of delta-opioid receptors abolishes the cardioprotective effect of ischemic preconditioning both in vivo and in vitro. An inhibition of kappa-opioid receptors abolishes the cardioprotective effect of ischemic preconditioning only in vitro. Agonists of mu-, delta1- delta- and kappa1-opioid receptors mimic the cardioprotective effect of preconditioning. Consequently, it can be argued that endogenous opioid peptides are triggers of ischemic preconditioning.

[Trigger mechanism of adaptive phenomenon of ischemic heart postconditioning].

Analysis of published data indicates on trigger role of protons, adenosine, opioids, bradykinin, calcitonin gene-related peptide, nitric oxide, epoxyeicosatrienoic acid, reactive oxygen species, hydrogen sulfide in ischemic heart postconditioning. It is shown that B-type natriuretic peptide, transforming growth factor-beta1, cardiotrophin-1, urocortin, acetylcholine, insulin and carbon monoxide can mimic postconditioning phenomenon.

[Significance of opioid receptors in regulation of cardiac tolerance in pathogenic impact of long-term ischemia-reperfusion in vivo].

The study aimed at investigation of the role of opioid receptor (OR) in regulation of cardiac tolerance to ischemia-reperfusion. Opioid receptor ligands and inhibitors were administered in vivo prior to coronary artery occlusion (45 min) and reperfusion (2 hrs). Occurring infraction size/area at risk (IS/AAR) ratio was determined. Pretreatment with the micro-OR agonists DAMGO and dermorphin H exerted no effect on the IS/AAR ratio. Activation of delta 1-OR by DPDPE did not alter cardiac tolerance in ischemia-reperfusion either. Pretreatment with the delta 2-OR agonists deltorphin D and deltorphin E or ORL1 receptor agonist nociceptin exerted no effect on the IS/AAR ratio. Stimulation of K-OR by selective agonists did not modify cardiac tolerance to ischemia-reperfusion. The delta 2-OR agonist deltorphin II significantly reduced the IS/AAR index. This effect was prevented by treatment with naltrexone, naloxone methiodide and the delta 2-OR antagonist naltriben but not by the delta 1-OR antagonist BNTX. The infarction-limiting effect of deltorphin II was also abolished by inhibition of protein kinase C (PKC) and mitochondrial Katp channels. Thus, the agonists of micro, delta 1, kappa, and ORL1 receptors in used doses did not affect cardiac tolerance in ischemia-reperfusion injury in vivo. The peripheral delta 2-OR activation induces infarction size reduction. Its infarction-reducing effect of deltorphin II is mediated via PKC activation and mitochondrial Katp, channel opening.