Effects of some radical scavengers on reperfusion-induced arrhythmias in the canine heart

Summary

In this study, using electron spin resonance (ESR), we investigated the relation at the time of reperfusion between free radicals originating from the mitochondria of the canine myocardium and arrhythmias induced by reperfusion as well as the effect of radical scavengers on both. The left anterior descending artery was ligated just below the first diagonal branch and then reperfused for 10 minutes in 48 adult mongrel dogs. The dogs were divided into six groups consisting of: 1) control group administered no radical scavengers (n=8), 2) SOD group (n=6) receiving superoxide dismutase (15,000 U/kg), 3) SOD+CAT group (n=6) receiving SOD (15,000 U/kg) and catalase (45,000 U/kg), 4) L-SOD group (n=6) receiving liposomal-encapsulated SOD (30,000 U/kg), 5) CV-3611 (2-O-octadecylascorbic acid) group (n=8) receiving CV-3611 (10 mg/kg), and 6) CoQ₁₀ group (n=6) receiving coenzyme Q₁₀ (10 mg/kg). SOD, SOD+CAT, L-SOD, CV-3611, and CoQ₁₀ were administered into the left atrium prior to reperfusion. The second lead of the electrocardiogram was continuously monitored during the experiment. The following results were obtained. 1) The relative intensity (RI) of the electron spin resonance signal of the mitochondria of the reperfused portion of the myocardium was smaller (p<0.025) in the SOD, SOD+CAT, L-SOD, CoQ₁₀ groups (1.08±0.36, 0.92±0.19, 0.91±0.11, and 0.81 ±0.09, respectively) than in the control group (1.70±0.20). 2) Effects of radical scavengers on ventricular arrhythmias: The disappearance time was (p<0.025) shorted in the SOD, SOD+CAT, L-SOD, and CoQ₁₀ groups (82±16, 86±10, 82 ±19, and 131±63 sec, respectively) as compared to the control group (304±71 sec). Also, SOD, SOD+CAT, L-SOD, and CoQ₁₀ reduced the number of episodes of ventricular tachycardia (VT) and total ventricular premature contractions compared to that of the controls, and also significantly shortened the maximum VT duration. In addition, the time in normal sinus rhythm was prolonged. 3) RI and the time for disappearance of ventricular arrhythmias were positively correlated (r=0.7827, p<0.05). The above results suggest that the administration of various kinds of radical scavengers such as SOD can limit the development of reperfusion arrhythmias, and that the generation of free radicals in the mitochondria of the myocardium is suppressed by these interventions, resulting in attenuation of cellular injury and preservation of mitochondrial function.