© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Differential roles of myocardial Ca2+ channels and Na+/Ca2+ exchange in myocardial reperfusion injury in open chest dogs: relative roles during ischemia and reperfusion
Division of Cardiology/Hypertension, Department of Medicine and the Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
* Corresponding author. Medical College of Wisconsin, Department of Medicine, Division of Cardiovascular Medicine, 9200 W. Wisconsin Ave., Milwaukee, WI 53226. Tel. (414) 2576697, Fax (414) 2577291, E-mail ssmart@post.its.mcw.edu
Objective: Compare the roles of Ca2+ channels and Na+/Ca2+ exchange in reperfusion injury (reperfusion ventricular fibrillation and myocardial stunning). Methods: Open chest dogs undergoing 15 minutes of left anterior descending coronary artery occlusion and 3 hours of reperfusion were randomized to controls or intracoronary infusions of the respective antagonists, nifedipine (50 µg/min) or amiloride (5 mg/min), according to five protocols: (A) 40 minutes before occlusion to 30 minutes after reperfusion; (B) 2 minutes before to 5 minutes after reperfusion; (C) 10 minutes before to 10 minutes after reperfusion (two step infusion for nifedipine only 5 µg/min during occlusion and 50 µg/min after reperfusion); and (D) 0 to 30 minutes after reperfusion. The role of Ca2+ channels was further investigated by infusing the agonist, Bay K 8644 (50 µg/min), alone or simultaneously with any protocol B, C, or D infusions altering both reperfusion ventricular fibrillation and myocardial stunning. Results: Effects of the agents on injury did not result from hemodynamic effects or alterations in blood flow. Amiloride had no effect on ventricular fibrillation. Only protocol A infusion of amiloride prevented myocardial stunning. In contrast, protocol A and B infusions of nifedipine prevented both myocardial stunning (p = ns vs. baseline, p<0.01 vs. control) and ventricular fibrillation (0%, p<0.01). Protocol C prevented reperfusion ventricular fibrillation, but not stunning (p = ns vs. control). Protocol D did not alter injury. Bay K 8644 co-treatment reversed the effects of Protocol B infusion of nifedipine. Ventricular fibrillation was common and postischemic function worst in dogs treated with Bay K 8644 alone (protocol B). Conclusion: Myocardial Ca2+ channels contribute to both reperfusion ventricular fibrillation and stunning, whereas Na+/Ca2+ exchange contributes only to stunning. Inhibitors of myocardial Ca2+ channels are protective when infused in high doses just before reperfusion, whereas the efficacy of Na+/Ca2+ exchange inhibitors is dependent on pretreatment.
KEYWORDS Dogs; Amiloride; Nifedipine; Myocardial contraction; Myocardial ischemia; Reperfusion arrhythmias; Reperfusion injury; Stunned myocardium
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