1-3-dimethylthiourea and Arrhythmias--Cardiac

The role of oxygen-derived free radicals in reperfusion arrhythmias was investigated in open-chest anesthetized dogs. The left anterior descending coronary artery was cannulated and perfused by an arterial bypass shunt. Ischemia was produced for 15 min by shunt occlusion and retrograde diversion of collateral blood flow. Dogs (n = 12) were treated with saline, N-(2-mercaptopropionyl)glycine (50 mg/kg), deferoxamine (10 mg/kg), superoxide dismutase (15,000 U/kg) plus catalase (55,000 U/kg), or dimethylthiourea (500 mg/kg). All agents were infused intravenously for 1 h starting 30 min before occlusion and continuing for 5 min of reperfusion. There were no differences in mean arterial blood pressure, heart rate, antegrade coronary flow, retrograde coronary flow, or size of the risk region among the five treatment groups. None of the dogs developed ventricular fibrillation during occlusion, whereas 88% of the 60 dogs fibrillated upon reperfusion. The antioxidant interventions did not alter the incidence of reperfusion-induced ventricular fibrillation compared with the saline-treated controls. The results suggest that free radicals do not play a role in lethal canine reperfusion arrhythmias.

Topics: Animals; Antioxidants; Arrhythmias, Cardiac; Blood Pressure; Catalase; Coronary Circulation; Coronary Vessels; Deferoxamine; Dogs; Electrocardiography; Female; Free Radicals; Heart Rate; Male; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Superoxide Dismutase; Thiourea; Time Factors; Tiopronin; Ventricular Fibrillation

The effects of perfusate calcium reduction, allopurinol and dimethylthiourea on reperfusion-induced arrhythmias and purine wash-out in isolated rabbit and rat hearts were compared. The overall incidence of reperfusion-induced ventricular tachycardia (VT) was 88% and 94% and that of ventricular fibrillation (VF) was 44% and 88% in the control rabbit and rat hearts, respectively. VF was reduced to 10% and 0% in rat and rabbit hearts subjected to perfusate calcium reduction (0.4 mM for 1 min before ischemia and for 1 min before and throughout reperfusion), respectively. In allopurinol, 1 mM, perfused rat hearts the overall incidence of VF was not changed and only the incidence of a sustained VF (that lasting for at least 10 min) was reduced. VT and VF were prevented in allopurinol-perfused rabbit hearts. Dimethylthiourea, 10 mM, reduced the incidence of VF in rat hearts to 16% and did not significantly affect VT and VF in rabbit hearts. In untreated rat hearts, the major purine compounds washed out upon reperfusion were inosine, hypoxanthine, xanthine and urate. Allopurinol augmented the wash-out of adenosine and abolished that of xanthine and urate. In untreated rabbit hearts, the major purine washed out were inosine, adenosine and hypoxanthine. Allopurinol did not cause further increase in adenosine wash-out in rabbit hearts. We speculate that: (1) calcium mediated arrhythmogenic mechanism is operating both in reperfused rat and rabbit heart; (2) free radical mediated mechanism is of an importance only in rat heart; (3) neither a decreased free radical production secondary to xanthine oxidase inhibition nor the augmentation of adenosine wash-out is a likely explanation for the antiarrhythmic effect of allopurinol in reperfused hearts; and (4) high level of myocardial adenosine accumulation during ischemia, probably secondary to low xanthine oxidase activity, may play a role of a natural defence mechanism in ischemic/reperfused rabbit heart.

Topics: Adenosine; Allopurinol; Animals; Arrhythmias, Cardiac; Calcium; Female; Free Radicals; Heart; Incidence; Male; Myocardium; Oxidation-Reduction; Purines; Rabbits; Rats; Rats, Wistar; Receptors, Purinergic P1; Reperfusion Injury; Tachycardia, Ventricular; Thiourea; Xanthine Oxidase