Favorable versus detrimental cardiovascular responses to intermittent hypoxia conditioning (IHC) are heavily dependent on experimental or pathological conditions, including the duration, frequency and intensity of the hypoxia exposures. Recently, we demonstrated that a program of moderate, normobaric IHC (FIO2 9.5-10% for 5-10 min/cycle, with intervening 4 min normoxia, 5-8 cycles/day for 20 days) in dogs afforded robust cardioprotection against infarction and arrhythmias induced by coronary artery occlusion-reperfusion, but this protection has not been verified in other species. Accordingly, in this investigation cardio- as well as vasoprotection were examined in male Wistar rats completing the normobaric IHC program or a sham program in which the rats continuously breathed atmospheric air. Myocardial ischemia and reperfusion (IR) was imposed by occlusion and reperfusion of the left anterior descending coronary artery in in situ experiments and by subjecting isolated, perfused hearts to global ischemia-reperfusion. Cardiac arrhythmias and myocardial infarct size were quantified in in situ experiments. Endothelial function was evaluated from the relaxation to acetylcholine of norepinephrine-precontracted aortic rings taken from in situ IR experiments, and from the increase in coronary flow produced by acetylcholine in isolated hearts. IHC sharply reduced cardiac arrhythmias during ischemia and decreased infarct size by 43% following IR. Endothelial dysfunction in aorta was marked after IR in sham rats, but not significant in IHC rats. Similar findings were found for the coronary circulations of isolated hearts. These findings support the hypothesis that moderate, normobaric IHC is cardio- and vasoprotective in a rat model of IR.
The present paper shows the arrhythmogenic effect of a direct induction of lipid peroxidation (LP) on isolated auricles; it is demonstrated that preendured stress potentiates this effect, while antioxidants prevent it. Subsequently, in studying the mechanism of the LP arrhythmogenic effect it was established that stress, like the LP induction, disorders the activity of Na, K-ATPase and accelerates thermodenaturation of this enzyme which plays a key role in maintaining the transmembrane potential and the electrical stability of the heart. Antioxidants prevent the enumerated shifts. Based on these data, the antioxidant BHT was successfully applied for prevention of the fall in cardiac fibrillation threshold in stress and experimental myocardial infarction, and also for prevention of cardiac fibrillation itself under acute ischemia and reoxygenation of the heart.
In intact August rats, the cardiac contractile function at rest was by 76% higher than in Wistar rats, while their hearts, both intact and after acute myocardial infarction, were more resistant to isometric load than the hearts of Wistar rats. Postinfarction mortality in August rats was 18% vs. 70% in Wistar rats. Adrenoreactivity of the myocardium in August rats was decreased compared to that in Wistar rats. These peculiarities can determine high resistance of August rats to myocardial infarction.
Analysis of contribution of sympathetic and parasympathetic systems into heart rate variability carried out using atenolol and atropine showed that August rats are characterized by enhanced tone of the sympathetic system and reduced tone of the parasympathetic system compared to Wistar rats. Reduced tone of the parasympathetic system is also confirmed by lower sensitivity of the baroreflex. Blockade of NO synthesis with Nw-nitro-L-arginine more markedly increased blood pressure variability in August rats compared to Wistar rats. The data attest to a certain rigidity of the autonomic cardiovascular regulation in August rats.
As differentiated from Wistar rats, myocardial ischemia and reperfusion produce no ventricular fibrillation in August rats. Pretreatment with nitric oxide synthase inhibitor Nw-nitro-L-arginine increased mortality rate in August rats with acute myocardial infarction from 20 to 40%. Under these conditions mortality rate in Wistar rats increased from 50 to 71%. Interstrain differences in the resistance of these animals to the arrhythmogenic effect of ischemia are probably associated with higher activity of the nitric oxide system in August rats compared to Wistar rats.
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