The effects of diltiazem and reduced serum ionized calcium on ischemic ventricular fibrillation in the dog.
Calcium influx blockers reportedly suppress ventricular arrhythmias during acute ischemia. We therefore studied the effects of diltiazem and reduced serum ionized calcium on ventricular fibrillation (VF) in a reversible ligation model. VF was produced at 15-minute intervals by simultaneous occlusion of the left anterior descending and circumflex arteries of 31 dogs. Time from coronary occlusion to onset of VF showed no significant variation during 15 consecutive trials in six dogs that received saline alone. Intravenous infusion of diltiazem (0.02 mg/kg per min) markedly delayed the onset of VF in each of 10 dogs (P less than 0.0001). Mean VF latency increased from 138 to 295 seconds during a 45-minute diltiazem infusion, declined exponentially when the infusion ceased, and was strongly correlated with serum diltiazem concentration (r = 0.96, P less than 10(-6)). In five dogs, hemodynamic measurements, including coronary venous blood flow, were performed during each occlusion. The increase in VF latency by diltiazem was not due to increased coronary flow during occlusion or to reduction of left ventricular (LV) mechanical work. In six dogs, mean serum ionized calcium, [Ca++], was reduced from 1.11 to 0.59 mM by infusion of sodium citrate. Citrate infusion increased mean VF latency from 155 to 243 seconds, and the increase observed in each dog was correlated (r = 0.84, P less than 10(-6)) with the reduction in [Ca++]. VF latency was unaffected by lidocaine in nine dogs. The antifibrillatory effect of diltiazem during global LV ischemia may be an electrophysiological phenomenon related to reduction of cellular calcium influx.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000503:physiopathology; D008012:Lidocaine / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology*
D001552:Benzazepines; D002951:Citrates; D019343:Citric Acid; D008012:Lidocaine; D004110:Diltiazem; D002118:Calcium