S C Smart1, K B Sagar, D C Warltier. 1. Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA. ssmart@post.its.mcw.edu
Abstract
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 micrograms/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 micrograms/min during occlusion and 50 micrograms/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 micrograms/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.
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 micrograms/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 micrograms/min during occlusion and 50 micrograms/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 micrograms/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.
Authors: Marta Regueiro-Purriños; Felipe Fernández-Vázquez; Armando Perez de Prado; Jose R Altónaga; Carlos Cuellas-Ramón; Jose M Ajenjo-Silverio; Asuncion Orden; Jose M Gonzalo-Orden Journal: J Am Assoc Lab Anim Sci Date: 2011-01 Impact factor: 1.232