Robb-Nicholson C, Currie W D, Wechsler A S
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Circulation. 1978 Sep;58(3 Pt 2):I119-24.
This study evaluates the metabolic and physiologic effects of Verapamil on isolated, perfused rat hearts subjected to 1 hour of global ischemia. Hearts were perfused with a modified Krebs-Henseleit bicarbonate buffer with glucose. During working heart perfusion, mean aortic systolic pressure, heart rate, and aortic and coronary flows were measured. Cardiac output and minute work were calculated. In three groups of eight hearts, 60-minute global ischemia was followed by a 40-minute reperfusion to assess physiologic recovery. Three groups of 11 hearts were assayed for myocardial high-energy phosphates after ischemia. Untreated hearts recovered less than 15% of function and lost 50% of their high-energy phosphate stores. Hearts treated with Verapamil (2 microg/cc) prior to ischemia recovered greater than 85% of function and retained normal adenosine triphosphate (ATP) and 40% decreased creatine phosphate (CP) levels. The metabolic and physiologic effects of Verapamil lasted 20 minutes longer than potassium, possibly related to membrane binding and dissociation of Verapamil. Verapamil was shown to have cardioplegic and protective effects, both probably secondary to inhibition of calcium flux across the sarcolemmal membrane.
本研究评估了维拉帕米对经历1小时全心缺血的离体灌注大鼠心脏的代谢和生理效应。心脏用含葡萄糖的改良克雷布斯-亨泽莱特碳酸氢盐缓冲液灌注。在工作心脏灌注期间，测量平均主动脉收缩压、心率以及主动脉和冠状动脉血流量。计算心输出量和每分功。在三组每组8个心脏中，60分钟全心缺血后进行40分钟再灌注以评估生理恢复情况。三组每组11个心脏在缺血后检测心肌高能磷酸盐。未经处理的心脏功能恢复不到15%，其高能磷酸盐储备损失50%。缺血前用维拉帕米（2微克/立方厘米）处理的心脏功能恢复超过85%，并保留正常的三磷酸腺苷（ATP）水平，磷酸肌酸（CP）水平降低40%。维拉帕米的代谢和生理效应比钾持续长20分钟，这可能与维拉帕米的膜结合和解离有关。已证明维拉帕米具有心脏停搏和保护作用，两者可能均继发于对跨肌膜钙通量的抑制。
