Smart S C, Sagar K B, Warltier D C
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.
Cardiovasc Res. 1997 Dec;36(3):337-46. doi: 10.1016/s0008-6363(97)00187-9.
Compare the roles of Ca2+ channels and Na+/Ca2+ exchange in reperfusion injury (reperfusion ventricular fibrillation and myocardial stunning).
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.
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).
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.
比较钙通道和钠/钙交换在再灌注损伤（再灌注性室颤和心肌顿抑）中的作用。
将接受15分钟左前降支冠状动脉闭塞和3小时再灌注的开胸犬随机分为对照组或根据五种方案进行冠状动脉内输注各自的拮抗剂，硝苯地平（50微克/分钟）或阿米洛利（5毫克/分钟）：（A）闭塞前40分钟至再灌注后30分钟；（B）再灌注前2分钟至再灌注后5分钟；（C）再灌注前10分钟至再灌注后10分钟（硝苯地平两步输注，闭塞期间仅5微克/分钟，再灌注后50微克/分钟）；以及（D）再灌注后0至30分钟。通过单独输注激动剂Bay K 8644（50微克/分钟）或与任何改变再灌注性室颤和心肌顿抑的方案B、C或D输注同时进行，进一步研究钙通道的作用。
这些药物对损伤的影响并非源于血流动力学效应或血流改变。阿米洛利对室颤无影响。仅方案A输注阿米洛利可预防心肌顿抑。相比之下，方案A和B输注硝苯地平可预防心肌顿抑（与基线相比p = 无显著差异，与对照组相比p < 0.01）和室颤（0%，p < 0.01）。方案C可预防再灌注性室颤，但不能预防心肌顿抑（与对照组相比p = 无显著差异）。方案D未改变损伤。Bay K 8644联合治疗可逆转方案B输注硝苯地平的作用。单独用Bay K 8644治疗的犬（方案B）室颤常见且缺血后功能最差。
心肌钙通道对再灌注性室颤和心肌顿抑均有作用，而钠/钙交换仅对心肌顿抑有作用。心肌钙通道抑制剂在再灌注前大剂量输注时具有保护作用，而钠/钙交换抑制剂的疗效取决于预处理。
