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A course of treatment (16 mg/kg orally during 5 days) by Aralia mandshurica or Rhodiola rosea extracts reduced the incidence of ischemic and reperfusion ventricular arrhythmias during 10-min ischemia and 10-min reperfusion. Extracts of Eleutherococcus senticosus, Leuzea carthamoides, and Panax ginseng did not change the incidence of ischemic and reperfusion arrhythmias. Chronic treatment by aralia, rhodiola, and eleutherococcus elevated the ventricular fibrillation threshold in rats with postinfarction cardiosclerosis. Ginseng and leuzea did not change this parameter in rats with postinfarction cardiosclerosis.

It has been established that pretreatment with the selective mu-opioid receptor (OR) agonist DALDA (0.1 mg/kg, i.v.) or the selective delta1-OR agonists DPDPE (0.09 mg/kg) and/or (-)-TAN-67 (0.08 mg/kg) has no effect on the incidence of ventricular arrhythmias induced by a 10-min coronary artery occlusion and a 10-min reperfusion in ketamine-anesthetized rats. In contrast, the pretreatment with the selective delta2-OR agonist deltorphin II (0.12 mg/kg) and the proposed delta2-OR agonists deltorphin D (0.3 mg/kg) and/or dermorphin H (0.23 mg/kg) increases cardiac resistance to the arrhythmogenic action of acute ischemia and reperfusion. Administration of the mixed mu- and delta-OR agonist dalargin (0.12 mg/kg) 15 min before the coronary artery ligation abolished only the reperfusive ventricular fibrillation. It is concluded that peptidergic stimulation of delta2-ORs can be used as a new means of increasing cardiac tolerance to the arrhythmogenic effects of acute ischemia and reperfusion.

Preliminary selective blockade of micro, delta1, delta2, kappa1, and kappa2 opioid receptors proved to have no effect on the incidence of ventricular arrhythmias during a 10-min coronary occlusion and subsequent reperfusion in ketamine-anesthetized rats. We propose that the endogenous opioid system has no considerable role in regulation of heart resistance to the arrhythmogenic effect of short-term local ischemia and subsequent reperfusion.

Preliminary selective block of mu-, delta1-, delta2-, and kappa-opioid receptors had no effect on the incidence of ventricular arrhythmias during 10-min coronary occlusion-reperfusion in ketamine-narcotized rats. Repetitive short-term immobilization of rats for 2 weeks improved heart resistance to the arrhythmogenic action of coronary occlusion and reperfusion. Selective mu-opioid receptor antagonist CTAP completely abolished, while selective delta- and kappa-opioid receptor antagonists did not modulate the antiarrhythmic effect of adaptation. Probably, endogenous agonists of mu-opioid receptors play an important role in the adaptive improvement of heart resistance to arrhythmogenic factors, but are insignificant for the modulation of heart resistance to the arrhythmogenic action of short-term local ischemia-reperfusion in non-adapted animals.

Pretreatment with a selective kappa1 opioid receptor (OR) agonist (-)-U-50,488 (1 mg/kg, i.v.) prevented the development of arrhythmias induced by occlusion (10 min) and reperfusion (10 min) in ketamine anesthetized rats, while the treatment with a less active enantiomer (+)-U-50,488 in the same dose produced no such effects. Preliminary intravenous administration of a selective kappa1 OR antagonist norbinaltorphimine (9 mg/kg) fully abolished the antiarrhythmic effect of (-)-U-50,488, while the kappa2 OR antagonist quadazocine (3 mg/kg) did not eliminate this effect. The injections of norbinaltorphimine or quadazocine alone did not influence the incidence of model arrhythmias caused by the occlusion and reperfusion. It was concluded that kappa1 OR stimulation favors an increase in cardiac tolerance to the arrhythmogenic action of occlusion and reperfusion.

It has been found that pretreatment with ATP-dependent potassium channel (KATP-channel) opener, BMS 180448 (3 mg/kg, intravenously), increases cardiac resistance against arrhythmogenic action of coronary artery occlusion and reperfusion in anaesthetized rats. However, BMS 180448 induced a decrease in ventricular fibrillation threshold in rats postinfarction cardiac fibrosis. This effect was completely abolished by administration of the KATP-channel inhibitor, glibenclamide. By contrast, coadministration of BMS 180448 and selective sarcolemmal KATP-channel inhibitor, HMR 1098, promoted an increase in ventricular fibrillation threshold in rats with postinfarction cardiac fibrosis before normal value. The selective mitochondrial KATP-channel opener, diazoxide, also exacerbated a decrease in ventricular fibrillation threshold induced by postinfarction cardiac sclerosis. But after depletion of endogenous catecholamine storage by pretreatment with guanthidine, diazoxide, on the contrary, elevated the ventricular fibrillation threshold. It has been suggested that stimulation of mitochondrial ATP-sensitive potassium channels promotes an elevation in electrical stability of the heart, whereas opening of sarcolemmal KATP-channel increases a possibility of ventricular arrhythmias.