Henry P D, Wahl A M
Eur Heart J. 1983 Nov;4(11):819-22. doi: 10.1093/oxfordjournals.eurheartj.a061404.
Calcium blocking agents may protect the ischaemic heart by reducing ventricular afterload and cardiac contractility, or by augmenting myocardial perfusion. To determine whether protection is mediated in part by mechanisms unrelated to myocardial work and perfusion, we examined effects of diltiazem and nitrendipine on unperfused myocardium subjected to hypoxia. Rabbit right ventricular papillary muscles were mounted in a myograph containing Krebs buffer equilibrated at 37 degrees C with 95% O2-5% CO2. During brief electrical pacing at a frequency of 12 min-1, a preload of 1363 +/- 60 mg produced a maximal isometric force development of 4892 +/- 273 mg (SE; n = 113). After 60 min without pacing, the quiescent muscles were pre-equilibrated randomly for 20 min without drug for control (C = 38), or with 10(-6) diltiazem (n = 38) or 10(-6) mol l-1 nitrendipine (n = 38). Changes in resting force during equilibration did not exceed +/- 12 mg. Subsequent sudden de-oxygenation with 95% N2-5% CO2 evoked in controls an increase in force beginning after 16 +/- 1 min. The onset of hypoxic contracture was significantly (P less than 0.1) delayed in treated muscles and started after 31 +/- 3 min with diltiazem and after 23 +/- 2 min with nifedipine. Peak contracture was significantly (P less than 0.1) inhibited by diltiazem and nitrendipine compared to controls, respectively values averaging 264 +/- 22 mg, 480 +/- 44 mg and 895 +/- 70 mg. Thus, calcium blockers delayed and suppressed hypoxic contracture in quiescent myocardium, demonstrating that the drugs acted directly on cardiac muscle in the absence of rhythmic electrical and mechanical activity.
钙阻滞剂可通过降低心室后负荷和心肌收缩力，或通过增加心肌灌注来保护缺血心脏。为了确定这种保护作用是否部分由与心肌做功和灌注无关的机制介导，我们研究了地尔硫卓和尼群地平对缺氧未灌注心肌的影响。将兔右心室乳头肌安装在含有用95% O₂ - 5% CO₂在37℃平衡的 Krebs 缓冲液的肌动描记器中。在以12次/分钟的频率进行短暂电刺激期间，1363±60mg的前负荷产生了4892±273mg（标准误；n = 113）的最大等长力。在无刺激60分钟后，将静止的肌肉随机预平衡20分钟，一组不加药物作为对照（C = 38），一组加入10⁻⁶地尔硫卓（n = 38）或10⁻⁶mol/L尼群地平（n = 38）。平衡期间静息力的变化不超过±12mg。随后用95% N₂ - 5% CO₂突然脱氧，对照组在16±1分钟后开始出现力增加。在用药的肌肉中，缺氧挛缩的开始明显延迟（P < 0.1），用地尔硫卓的肌肉在31±3分钟后开始，用硝苯地平的肌肉在23±2分钟后开始。与对照组相比，地尔硫卓和尼群地平分别显著抑制了挛缩峰值（P < 0.1），平均峰值分别为264±22mg、480±44mg和895±70mg。因此，钙阻滞剂延迟并抑制了静止心肌中的缺氧挛缩，表明这些药物在没有节律性电活动和机械活动的情况下直接作用于心肌。
