Effects of calcium channel blocking agents on reperfusion arrhythmias

The effect of the calcium antagonists nifedipine (NF) and diltiazem (DT) on reperfusion after release of circumflex coronary artery (CX) occlusion was studied in open-chest dogs. Dogs were randomized to receive a bolus of 5 micrograms/kg NF (seven dogs), 1 microgram/kg NF (nine dogs), or vehicle (nine dogs). After bolus, high and low dose NF dogs were infused with 1 microgram/kg/min NF. All dogs then underwent 30 minutes CX occlusion followed by reperfusion. Dogs that did not develop ventricular fibrillation (VF) in the first 10 minutes of reperfusion were considered survivors. NF caused a dose-related increase in CX blood flow and decrease in mean arterial pressure (MAP), significant at the higher dose. Reperfusion VF occurred in five of nine low dose NF dogs, five of seven high dose NF dogs, and five of nine controls. Another 21 dogs were randomized to receive a bolus of 0.2 mg/kg DT (11 dogs) or vehicle (10 dogs). Infusion rates (and an additional bolus injection, if necessary) were chosen to produce a 10 to 20 mm Hg drop in MAP. CX occlusion and reperfusion were performed as above. Reperfusion VF occurred in 9 of 11 DT dogs vs 8 of 10 controls. Thus neither nifedipine nor diltiazem enhanced survival during reperfusion of myocardium previously subjected to 30 minutes of ischemia.