Bush L R, Li Y P, Shlafer M, Jolly S R, Lucchesi B R
J Pharmacol Exp Ther. 1981 Sep;218(3):653-61.
The protective effects of diltiazem, a calcium channel blocker, were studied in isolated, blood-perfused cat hearts subjected to 60 or 90 min of global ischemia, followed by reperfusion of 60 or 120 min, respectively. Ischemia-induced alterations of left ventricular (LV) developed pressure (DP) and compliance, measured with an intraventricular fluid-filled latex balloon, were correlated with respiratory activity in vitro of mitochondria isolated from ischemic-reperfused LV myocardium. Nontreated isolated hearts sustained severe declines of LVDP as a result of 60 (-50 +/- 8%) and 90 min (-83 +/- 7%) of ischemia, whereas diltiazem-treated hearts demonstrated only minor losses of LVDP (-17 +/- 8 and -26 +/- 2%). Diltiazem prevented losses of compliance caused by 60 or 90 min of ischemia, which were severe in nontreated hearts after the latter period of ischemia. The progressive deterioration of mechanical function observed in nontreated hearts was paralleled by depressed mitochondrial oxygen consumption and respiratory control. The respiratory activity of mitochondria isolated from cat heart mitochondria. Diltiazem also prevented significant elevations of tissue and mitochondria Ca++ content, reflecting inhibition of Ca++ influx during ischemia and reperfusion. Also, recovery of ATP levels was greater after 60 min each of ischemia and reperfusion in diltiazem-treated hearts. Thus, diltiazem exerts direct, cardioprotective effects during myocardial ischemia, presumably by inhibiting transmembrane Ca++ fluxes.
研究了钙通道阻滞剂地尔硫䓬对离体、血液灌注的猫心脏的保护作用，这些心脏分别经历60或90分钟的全心缺血，随后分别再灌注60或120分钟。用室内充满液体的乳胶气球测量的缺血诱导的左心室（LV）舒张末压（DP）和顺应性改变，与从缺血再灌注的LV心肌分离的线粒体在体外的呼吸活性相关。未经处理的离体心脏由于60分钟（-50±8%）和90分钟（-83±7%）的缺血而导致LVDP严重下降，而地尔硫䓬处理的心脏仅表现出LVDP的轻微下降（-17±8和-26±2%）。地尔硫䓬可防止60或90分钟缺血引起的顺应性丧失，在后期缺血后未经处理的心脏中这种丧失很严重。在未经处理的心脏中观察到的机械功能的逐渐恶化与线粒体氧消耗和呼吸控制的降低平行。从猫心脏线粒体分离的线粒体的呼吸活性。地尔硫䓬还可防止组织和线粒体Ca++含量的显著升高，这反映了在缺血和再灌注期间对Ca++内流的抑制。此外，地尔硫䓬处理的心脏在缺血和再灌注各60分钟后ATP水平的恢复更大。因此，地尔硫䓬在心肌缺血期间发挥直接的心脏保护作用，可能是通过抑制跨膜Ca++通量。
