Przyklenk K, Kloner R A
Department of Internal Medicine, Harper Hospital, Detroit, Michigan 48201.
J Am Coll Cardiol. 1988 Mar;11(3):614-23. doi: 10.1016/0735-1097(88)91540-9.
Timely administration of verapamil has been shown to reduce indexes of ischemic injury in experimental models of prolonged coronary artery occlusion, yet its effect on contractile function of reversibly injured (that is, "stunned") myocardium remains unknown. The objective of the present study was to determine whether verapamil--administered either 30 min before coronary artery occlusion, at the time of reperfusion or 30 min after reperfusion--could attenuate the regional contractile dysfunction and alterations in high energy phosphate metabolism produced by 15 min of transient coronary artery occlusion in anesthetized, open chest dogs. All treatment groups exhibited passive systolic bulging during occlusion. In the control dogs receiving saline solution, segment shortening in the previously ischemic tissue averaged only 31 +/- 8% of normal baseline values after 3 h of reperfusion. In addition, endocardial adenosine triphosphate (ATP) stores were depleted by -8.7 +/- 0.8 nmol/mg cardiac protein to 26.5 +/- 1.1 nmol/mg protein, and endocardial creatine phosphate content increased by 9.6 +/- 4.3 nmol/mg cardiac protein over normal values. Pretreatment with verapamil essentially ablated the phenomenon of postischemic stunning: segment shortening was restored to 115 +/- 8% of normal after 3 h of reflow (p less than 0.01 versus control), endocardial ATP stores were partially preserved (30.6 +/- 1.2 nmol/mg protein; p less than 0.05 versus control) and creatine phosphate overshoot was blunted (endocardial creatine phosphate content decreased by -5.6 +/- 2.9 nmol/mg protein; p less than 0.05 versus control). Verapamil administered at or after reperfusion also attenuated postischemic contractile dysfunction: segment shortening for both groups recovered to 65 +/- 9% of baseline at 3 h after reperfusion (p less than 0.05 versus control). Verapamil given at or after reperfusion had no beneficial effect, however, on high energy phosphate stores. Thus, even when treatment was "delayed," that is, initiated at or after reperfusion, administration of verapamil significantly increased contractile function of the postischemic stunned myocardium.
在冠状动脉长时间闭塞的实验模型中，已证明及时给予维拉帕米可降低缺血损伤指标，但其对可逆性损伤（即“顿抑”）心肌收缩功能的影响尚不清楚。本研究的目的是确定在冠状动脉闭塞前30分钟、再灌注时或再灌注后30分钟给予维拉帕米是否能减轻麻醉开胸犬短暂冠状动脉闭塞15分钟所产生的局部收缩功能障碍和高能磷酸代谢改变。所有治疗组在闭塞期间均表现出被动收缩性膨出。在接受生理盐水的对照犬中，再灌注3小时后，先前缺血组织的节段缩短平均仅为正常基线值的31±8%。此外，心内膜三磷酸腺苷（ATP）储备减少了-8.7±0.8 nmol/mg心肌蛋白，降至26.5±1.1 nmol/mg蛋白，心内膜磷酸肌酸含量比正常值增加了9.6±4.3 nmol/mg心肌蛋白。维拉帕米预处理基本消除了缺血后顿抑现象：再灌注3小时后节段缩短恢复至正常的115±8%（与对照组相比，p<0.01），心内膜ATP储备部分得以保留（30.6±1.2 nmol/mg蛋白；与对照组相比，p<0.05），磷酸肌酸过冲现象减弱（心内膜磷酸肌酸含量减少了-5.6±2.9 nmol/mg蛋白；与对照组相比，p<0.05）。在再灌注时或再灌注后给予维拉帕米也减轻了缺血后收缩功能障碍：两组在再灌注后3小时节段缩短均恢复至基线的65±9%（与对照组相比，p<0.05）。然而，在再灌注时或再灌注后给予维拉帕米对高能磷酸储备没有有益作用。因此，即使治疗“延迟”，即在再灌注时或再灌注后开始，给予维拉帕米也能显著增强缺血后顿抑心肌的收缩功能。
