Smart S C, LoCurto A, el Schultz J, Sagar K B, Warltier D C
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.
J Am Coll Cardiol. 1995 Nov 1;26(5):1365-73. doi: 10.1016/0735-1097(95)00326-6.
This study sought to establish the effect of amiloride on stunned myocardium and to determine the role of hemodynamic alterations and inhibition of sodium/proton (Na+/H+) exchange and L-type cytosolic calcium (Ca2+) channels.
Amiloride is a nonspecific agent that may reduce reperfusion injury, but its effect on reversible dysfunction or stunned myocardium is unclear.
Ninety-seven open chest dogs undergoing 15 min of left anterior descending coronary artery occlusion and 3 h of reperfusion with monitoring of hemodynamic variables, systolic shortening and myocardial blood flow were randomized to seven intracoronary infusions: control dogs (5% dextrose, n = 16); low dose amiloride (1 mg/min, n = 14); high dose amiloride (5 mg/min) with (n = 12) and without (n = 16) atrial pacing; sodium nitroprusside (20 micrograms/min, n = 16); hexamethylene amiloride (a specific inhibitor of Na+/H+ exchange, 60 micrograms/min, n = 14); and nifedipine (a specific inhibitor of L-type Ca2+ channels, 5 micrograms/min, n = 9). Drug infusions were started 40 min before occlusion and stopped at 30 min after reperfusion.
Forty-three dogs were excluded because of ventricular fibrillation or high collateral flow. The incidence of ventricular fibrillation was similar in all groups to that in control dogs. Systolic shortening completely recovered (p = NS vs. baseline; p < 0.01 vs. control group) by 2 h after reperfusion in the low dose amiloride group and 30 min in the high dose group (p < 0.01 vs. low dose). High dose amiloride increased myocardial blood flow and had positive inotropic and negative chronotropic effects (p < 0.05 vs. control group). Atrial pacing did not attenuate recovery. The only effect of low dose amiloride was increased myocardial blood flow after reperfusion. Systolic shortening did not deteriorate after washout of drug effects. Sodium nitroprusside and nifedipine similarly increased myocardial blood flow, but systolic shortening never recovered. Hexamethylene amiloride had no hemodynamic effects, and systolic shortening never recovered.
Amiloride prevented the contractile dysfunction of myocardial stunning but did not prevent arrhythmias. Hemodynamic alterations, increased myocardial blood flow and inhibition of Na+/H+ exchange or L-type Ca2+ channels alone did not account for the improved function. Inhibition of Na+/Ca2+ exchange may be the mechanism of improved postischemic function.
本研究旨在确定阿米洛利对顿抑心肌的作用，并确定血流动力学改变、钠/氢（Na+/H+）交换抑制及L型胞浆钙（Ca2+）通道抑制的作用。
阿米洛利是一种非特异性药物，可能减轻再灌注损伤，但其对可逆性功能障碍或顿抑心肌的作用尚不清楚。
97只开胸犬，左前降支冠状动脉闭塞15分钟，再灌注3小时，同时监测血流动力学变量、收缩期缩短及心肌血流，随机分为7组冠状动脉内输注：对照组犬（5%葡萄糖，n = 16）；低剂量阿米洛利（1毫克/分钟，n = 14）；高剂量阿米洛利（5毫克/分钟），伴（n = 12）和不伴（n = 16）心房起搏；硝普钠（20微克/分钟，n = 16）；六亚甲基阿米洛利（Na+/H+交换特异性抑制剂，60微克/分钟，n = 14）；硝苯地平（L型Ca2+通道特异性抑制剂，5微克/分钟，n = 9）。药物输注在闭塞前40分钟开始，再灌注后30分钟停止。
43只犬因室颤或高侧支血流被排除。所有组室颤发生率与对照组相似。低剂量阿米洛利组再灌注后2小时收缩期缩短完全恢复（与基线相比p =无显著性差异；与对照组相比p < 0.01），高剂量组30分钟恢复（与低剂量组相比p < 0.01）。高剂量阿米洛利增加心肌血流，具有正性肌力和负性变时作用（与对照组相比p < 0.05）。心房起搏未减弱恢复。低剂量阿米洛利的唯一作用是再灌注后增加心肌血流。药物作用消除后收缩期缩短未恶化。硝普钠和硝苯地平同样增加心肌血流，但收缩期缩短从未恢复。六亚甲基阿米洛利无血流动力学作用，收缩期缩短从未恢复。
阿米洛利预防了心肌顿抑的收缩功能障碍，但未预防心律失常。血流动力学改变、心肌血流增加及单独抑制Na+/H+交换或L型Ca2+通道不能解释功能改善。抑制Na+/Ca2+交换可能是缺血后功能改善的机制。
