Nayler W G, Panagiotopoulos S, Elz J S, Sturrock W J
Am J Cardiol. 1987 Jan 30;59(3):75B-83B. doi: 10.1016/0002-9149(87)90086-5.
The mammalian myocardium exhibits a spectrum of damage during an ischemic episode. After relatively short periods of ischemia the damage is reversible, but with longer periods of ischemia the number of cells that are lethally injured increases. When coronary flow is restored the lethally injured cells become overloaded with Ca++ and fail to regenerate adenosine triphosphate. The calcium antagonists provide protection under these circumstances, but only if used prophylactically. When added only upon reperfusion the calcium antagonists slow, but do not inhibit, the excessive gain in Ca++ that occurs during postischemic reperfusion. Nicotine, in a concentration equivalent to that found in the plasma of smokers (0.15 microgram/ml), exacerbates the reperfusion-induced Ca++ gain. Treatment with the long-acting calcium antagonist, anipamil, on a once-daily basis attenuates the reperfusion-induced Ca++ gain in spontaneously hypertensive rats and its exacerbation by nicotine in Sprague Dawley rats. The prolonged oral administration of at least 1 calcium antagonist, verapamil (50 mg/kg body weight/day), causes a significant (p less than 0.001) depletion of left ventricular norepinephrine.
在缺血发作期间，哺乳动物的心肌会呈现出一系列损伤。在相对较短的缺血期后，损伤是可逆的，但随着缺血时间延长，遭受致命损伤的细胞数量会增加。当冠状动脉血流恢复时，遭受致命损伤的细胞会因钙离子过载而无法再生三磷酸腺苷。在这种情况下，钙拮抗剂可提供保护作用，但前提是要预防性使用。仅在再灌注时添加钙拮抗剂，虽能减缓但无法抑制缺血后再灌注期间钙离子的过度增加。尼古丁浓度相当于吸烟者血浆中的浓度（0.15微克/毫升）时，会加剧再灌注诱导的钙离子增加。长效钙拮抗剂阿尼帕米每日一次给药，可减轻自发性高血压大鼠再灌注诱导的钙离子增加以及尼古丁对斯普拉格-道利大鼠的这种加剧作用。至少一种钙拮抗剂维拉帕米（50毫克/千克体重/天）长期口服会导致左心室去甲肾上腺素显著（p＜0.001）耗竭。
