Anti-Inflammatory Effect of Atorvastatin on Primary Human Endothelial Cells Incubated under Genotoxic Load.

The level of cytokine expression was measured in human coronary artery (HCAEC) and internal thoracic artery (HITAEC) endothelial cells exposed to 500 ng/ml alkylating mutagen mitomycin C (MMC) and 5 µM atorvastatin. It was found that treatment of MMC-exposed HCAEC with atorvastatin decreased secretion of macrophage migration inhibitory factor (MIF), IL-8, and IL8 gene expression, but increased the expression of SERPINE1 gene encoding the PAI-1 protein. In atorvastatin-treated HITAEC, the concentration of MIF protein and the expression of the IL8 and SERPINE1 genes were reduced. We can conclude that atorvastatin prevents proinflammatory activation of endothelial cells cultured under conditions of genotoxic load. However, the molecular mechanisms of this effect require further research.

Effects of Deltorphin II and Its Retroenantio Analog on Cardiac Tolerance to Ischemia and Reperfusion.

Selective agonist of δ2-opioid receptors deltorphin II and its retroenantio analog (0.12 mg/kg intravenously) were preventively injected to male Wistar rats 15 min prior to 45-min coronary occlusion or 5 min before 120-min reperfusion. Administration of deltorphin II before artery occlusion and before reperfusion decreased the infarct size/area at risk ratio. Deltorphin II prevented the appearance of ischemia-provoked ventricular arrhythmias and exerted no effect on HR and BP (systolic and diastolic). The retroenantio analog of deltorphin II produced no antiarrhythmic or infarct-limiting effects, but reduced HR without affecting BP. Deltorphin II can be viewed as a promising prototype for a medicinal remedy to treat acute myocardial infarction.

[Prospects of Application of Remote Preconditioning at Heart Revascularization].

Remote ischemic preconditioning of the heart exerts anti-necrotic, antiarrhythmic, inotropic effects that have been demonstrated in clinical trials in cardiac surgery both in adults and children. However, so far there is no consensus between cardiologists regarding the impact of remote preconditioning on the incidence of intraoperative myocardial infarctions and mortality in the postoperative period. Until now there is no unanimity concerning choice of remote preconditioning protocol and timing of its application before cardiac surgery.

CB-Receptor Agonist HU-210 Mimics the Postconditioning Phenomenon of Isolated Heart.

CB receptor agonist HU-210 exhibits an infarction-limiting effect during in vitro reperfusion of the heart after focal ischemia. This effect is paralleled by a decrease in left-ventricular developed pressure and double product. In addition, HU-210 reduces end-diastolic pressure during the reperfusion period, which indirectly attests to reduced Ca2+ overload of cardiomyocytes.

[Neuroprotective and nephroprotective effects of remote postconditioning: Prospects for clinical use]. / Neiroprotektornyi i nefroprotektornyi éffekty distantnogo prekonditsionirovaniia. Perspektivy klinicheskogo primeneniia.

The results of experimental and clinical studies strongly suggest that remote ischemic preconditioning (RIP) has no neuroprotective effect during cardiac surgery performed under extracorporeal circulation. Remote preconditioning (RP) has no neuroprotective effect in hemorrhagic stroke. A randomized multicenter study is needed to evaluate the efficiency RIP in patients with ischemic stroke. RP reduces the severity of ischemia/reperfusion kidney injury during transplantation. RIP has been established to prevent contrast-induced nephropathy. There is a need for a multicenter trial to evaluate the efficiency of RIP in patients with abdominal aortic aneurysm repair. Analysis of the presented data indicates that RIP fails to prevent cardiorenal syndrome in infants and children during cardiac surgery. The data available in the literature on the capacity of RIP to provide nephroprotective effect in patients after coronary artery bypass surgery are discordant and indicative of the advisability of a multicenter study.

[CARDIOPROTRECTIVE EFFECT OF REMOTE POSTCONDITIONING: MECHANISMS AND POSSIBILITIES OF CLINICAL APPLICATION].

Experimental data indicate that postconditioning at a distance is an effective method for cardiac protection against reperfusion injury. Remote postconditioning prevents reperfusion necrosis and apoptosis of cardiomyocytes, decreases a probability of postinfarction remodeling of the heart. Cardioprotective effect of remote postconditioning depends on the release of tissue factor(s) increasing cardiac tolerance to long-term ischemia-reperfusion after transient ischemia. Clinical investigations show that postconditioning at a distance is an effective method for the prevention of reperfusion injury of the heart during coronary artery bypass surgery.

[Remote preconditioning phenomenon. prospects for use in pathology of lung and gastrointestinal tract].

The literature data on the effectiveness of remote ischemic preconditioning (RIP) in the prevention of lung injury are contradictory. Authors of some works argue that RIP prevents lung damage during surgical interventions, the authors of other publications claim that the RIP does not protect lung against pathological processes. It is obvious that there is an urgent need for multicenter, randomized trials aimed at studying RIP protective effects against pathological processes in lung. Also required is clinical evaluation of the effectiveness of RIP in the thromboembolism of pulmonary arteries, the transplantation of the lungs and intestinal infarction. Remote preconditioning prevents the intestine injury associated with abdominal aortic aneurysm repair. Experimental data indicate that RIP has the hepatoprotective effect during ischemia and reperfusion injury of liver, septic or haemorrhagic shock. The question of whether the DIP has a protective effect during ischemia-reperfusion of the pancreas remains open.

The cytokine response of human coronary artery endothelial cells treated with doxorubicin: results of an in vitro experiment.

The cytokine profile of primary coronary artery endothelial cells cultivated in the presence of doxorubicin (2 µg/ml and 6 µg/ml) was evaluated using enzyme-linked immunosorbent assay and qPCR. Cultivation of cells in the presence of these concentrations of doxorubicin for 24 h, upregulated expression of the following genes: IL6 (by 2.30 and 2.66 times, respectively), IL1B (by 1.25 and 3.44 times), and CXCL8 (by 6.47 times and 6.42 times), MIF (2.34 and 2.28 times), CCL2 (4.22 and 3.98 times). Under these conditions the following genes were downregulated: IL10, IL1R2, TNF. Cultivation of cells in the presence of doxorubicin (2 µg/ml and 6 µg/ml) for 24 h also increased the secretion of IL-6.

[PHENOMENON OF REMOTE PRECONDITIONING THE HEART AND ITS MAIN MANIFESTATIONS].

Remote ischemic preconditioning prevents reperfusion cardiomyocyte apoptosis and has the infarct-limiting effect which is maintained in the experiments on the isolated perfused heart. Remote preconditioning promotes to recovery the contractility of the heart during reperfusion, but did not affect the incidence of occlusion and reperfusion of ventricular arrhythmias. Remote preconditioning has a mild anti-inflammatory effect. Presented article is a review and formulated conclusions based on the published literature data.

[CHRONIC CONTINUOUS NOR-MOBARIC HYPOXIA AUGMENTS CELL TOLERANCE TO ANOXIA(REOXYGE-NATION: THE ROLE OF PROTEIN KINASES].

The study evaluated the role of protein kinase C, PI3-kinase and tyrosine kinases in the cardi-oprotective effect of the chronic continuous normobaric hypoxia (CCNH). Adaptation to CCNH was provided by placing the rats in an atmosphere with a low content of O2 (12 %) during 21 days. Anoxia-reoxygenation of isolated cardiomyocytes of intact rats caused the deaths of 16.5 % of the cells and the lactate dehydrogenase (LDH) release of them. A similar effect on isolated cardiomyocytes of adapted rats caused the death of only 6.8 % of the cells and less pronounced increase in LDH release. Preincubation of cells for 25 minutes with one of the protein kinases inhibitors: che-lerythrine (10 |mM/l); rottlerin (1 |j.M/l); genistein (50 |mM/l) eliminated the adaptive increase in cell survival and reduction of LDH release. Incubation of cells with PI3-kinase blocker wortman-nin (100 nM/l) had no effect on the percentage of cell death of adapted animals and LDH release from them after anoxia-reoxygenation. The authors believe that the cytoprotective effect of chronic normobaric hypoxia is realized through activation of protein kinase C-5 and tyrosine kinases. Kinase PI3 - is not involved in the implementation of protective actions CCNH.