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Unlabelled: The mechanisms of the protective effect of oligonucleotides (OGN) during pathological processes are poorlyunderstood. The goal of this work was to study the effect of OGN on arrhythmias induced by myocardial ischemia and reperfusion, and the HSP70 level in the heart. As a source of OGN was used the drug "Derinat" ("Technomedservis", Russia). In male Wistar rats were pre-treated the drug for 7 days (i/m, 7.5 mg/kg).The intensity of the arrhythmias was assessed by ECG during 10 min occlusion of the left coronary artery and subsequent 5 min of reperfusion. Protein HSP70 determined in the left ventricle of the heart by Western-blot analysis. During ischemia, this drug reduced duration of extrasystolia by 13 times and the incidence of ventricular tachycardia by 1.5 times. During reperfusion the drug reduced the incidence of ventricular fibrillation, a more than 2-fold, as compared with the control (respectively 23% vs 56%) and by 5 times its duration (8,4 ± 2,3 48,1 ± sec vs 18 7 sec). "Derinat" increased the HSP70 level in the heart by 65% compared with control., Conclusion: These data support the fact that the activation of HSP70 synthesis, induced by OGN is one of the mechanisms that increases the heart resistance to the ischemic and reperfusion damages.

Previously we have shown that adaptation to hypoxia (AH) is cardio- and vasoprotective in myocardial ischemic and reperfusion injury and this protection is associated with restriction of nitrosative stress. The present study was focused on further elucidation of NO-dependent mechanisms of AH by identifying specific NO synthases (NOS) that could play the major role in AH protection. AH was performed in a normobaric hypoxic chamber by breathing hypoxic gas mixture (9.5-10% O2) for 5-10 min with intervening 4 min normoxia (5-8 cycles daily for 21 days). Expression of neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) protein was measured in the left ventricular myocardium using Western blot analysis with respective antibodies. AH educed iNOS protein expression by 71% (p < 0.05) whereas eNOS protein expression tended to be reduced by 41% compared to control (p < 0.05). nNOS protein expression remained unchanged after AH. Selective iNOS inhibition can mimic the AH-induced protection. Therefore protective effects of AH could be at least partially due to restriction of iNOS and, probably, eNOS expression.

Diabetes mellitus (DM) increases the risk of sudden cardiac death, which suggests the involvement of arrhythmogenic mechanisms. Among other changes, DM causes cardiac autonomic neuropathy (CAN), but its role in electrophysiological myocardial remodeling is unclear. The objective of the present study was to test the effects of β-adrenergic blockade regarding ventricular spatiotemporal electrophysiological properties in an experimental DM model. Epicardial mapping (64-lead sock electrode array) was done in 13 control and 11 alloxan-induced DM rabbits. Activation times (AT), end of repolarization times (RT), and activation-repolarization intervals (ARI) were determined as dV/dt min during QRS, dV/dt max during T-wave, and RT-AT difference, respectively. The β-adrenergic blockade was produced by esmolol infusion (0.5 mg/kg, i.v.). It was found that the early-stage DM in rabbits was characterized by relatively mild changes in ventricular myocardium, which did not involve ventricular activation and the average duration of repolarization. The signature of this stage was the local prolongation of repolarization, which pertained to the RV apical region. The blockade of β-adrenergic receptors in healthy animals produced a ventricular spatiotemporal repolarization pattern similar to that observed in diabetic rabbits with the local apical prolongation of repolarization. On the other hand, the blockade of β-adrenergic receptors in diabetics prolonged the relatively short basal repolarization. It can be concluded that β-adrenergic blockade in healthy animals reproduced the early-stage DM effects on the spatiotemporal electrophysiological properties of the ventricular myocardium. This demonstrated the role which CAN could play in the electrical remodeling of ventricular myocardium in early-stage DM. [ABSTRACT FROM AUTHOR]