Kimura Y, Engelman R M, Rousou J, Flack J, Iyengar J, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110.
Heart Vessels. 1992;7(4):189-95. doi: 10.1007/BF01744603.
Intracellular Ca2+ accumulation is implicated in the pathogenesis of myocardial reperfusion injury. To study approaches designed to modify Ca2+ uptake during coronary revascularization after acute infarction, a pig heart surgical infarct model (left anterior descending artery occlusion for 60 min) was subjected to 60 min hypothermic potassium cardioplegic arrest, followed by 60 min of global reperfusion. Four groups of six hearts each were studied in a randomized manner, i.e., cardioplegia alone (control), cardioplegia + 10 microM diltiazem (Ca2+ slow channel blocker), cardioplegia + 10 microM trifluoperazine (TFP), (a Ca(2+)-calmodulin antagonist), and cardioplegia+diltiazem (10 microM) + TFP (10 microM). Left ventricular contractility (global and segmental), metabolism (coronary blood flow and O2 consumption), and creatine kinase generation were measured during reperfusion. Both the Ca2+ channel blocker, diltiazem, and the calmodulin antagonist, TFP, improved myocardial global and regional function as well as myocardial metabolism. While diltiazem better restored global and regional contractility, trifluoperazine had a greater effect on coronary blood flow and myocardial oxygen consumption. Enzyme release and lipid peroxidation were equally moderated by both drugs. From this study it can be concluded that Ca2+ influx does play a role in ischemic and reperfusion injury. The mechanisms of its effect are complex, but can be successfully antagonized by Ca2+ blockers as well as by calmodulin antagonists, with improved myocardial preservation.
细胞内钙离子蓄积与心肌再灌注损伤的发病机制有关。为了研究旨在改变急性梗死冠状动脉血运重建期间钙离子摄取的方法，对猪心脏手术梗死模型（左前降支动脉闭塞60分钟）进行60分钟低温钾停搏，随后进行60分钟全心再灌注。以随机方式研究四组，每组六只心脏，即单纯停搏液（对照组）、停搏液+10微摩尔地尔硫䓬（钙离子慢通道阻滞剂）、停搏液+10微摩尔三氟拉嗪（TFP，一种钙调蛋白拮抗剂）以及停搏液+地尔硫䓬（10微摩尔）+TFP（10微摩尔）。在再灌注期间测量左心室收缩性（整体和节段性）、代谢（冠状动脉血流量和氧消耗）以及肌酸激酶生成。钙离子通道阻滞剂地尔硫䓬和钙调蛋白拮抗剂TFP均改善了心肌整体和局部功能以及心肌代谢。虽然地尔硫䓬能更好地恢复整体和局部收缩性，但三氟拉嗪对冠状动脉血流量和心肌氧消耗的影响更大。两种药物对酶释放和脂质过氧化的抑制作用相当。从这项研究可以得出结论，钙离子内流在缺血和再灌注损伤中确实起作用。其作用机制复杂，但可通过钙离子阻滞剂以及钙调蛋白拮抗剂成功拮抗，从而改善心肌保护。
