Kolodgie F D, Farb A, Litovsky S H, Narula J, Jeffers L A, Lee S J, Virmani R
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington DC 20306-6000, USA.
J Mol Cell Cardiol. 1997 Sep;29(9):2403-14. doi: 10.1006/jmcc.1997.0476.
The role of physiologic estrogen levels (pg) on post-ischemic myocardial function was studied in the isolated working rat heart without (n=28, experiment No. 1) or with (n=15, experiment No. 2) preconditioning. For experiment No. 1, female ovariectomized rats were treated with placebo (n=19) or 17beta-estradiol (E2, n=9; chronic E2), and 14 days later hearts were removed and perfused with modified Krebs-Henseleit buffer in vitro. In nine placebo-treated rats, E2 was administered at 20 min prior to ischemia (acute E2). The hearts were subjected to 15 min of global ischemia and 20 min of reflow. In experiment No. 2, ovariectomized rats were treated with placebo (n=8) or 17beta-E2 (chronic E2, n=7). In this experiment, hearts were first preconditioned and then subjected to 20 min of sustained ischemia followed by 20 min of reflow. Global ischemia was produced by clamping the aorta and restricting left atrial flow so that coronary flow was reduced to zero; hemodynamics were continuously monitored throughout the study. Aortic flow, coronary flow, cardiac output, and dP/dt were assessed at baseline, at the end of the ischemic period, and during reflow. The severity of ischemia was measured by post-ischemic release of lactate, lactate dehydrogenase, and creatine kinase and was similar among all groups in each study. In experiment No. 1, recovery of aortic flow, cardiac output, and dP/dt following reperfusion, was significantly improved in rats treated with chronic E2 (P<0.05); acute E2 had no significant benefit. Post-ischemic recovery of coronary flow was not significantly affected. In experiment No. 2, chronic E2 treatment also significantly improved post-ischemic recovery of cardiac function in preconditioned hearts when compared with controls (P<0. 05). In summary, E2 replacement in ovariectomized rats improves contractile function following global ischemia and reflow; cardioprotection by estrogen was observed over and above that conferred by ischemic preconditioning. Since the cardioprotective effect of E2 was independent of a significant improvement in coronary flow a direct effect of the hormone on the cardiac myocytes is postulated.
在离体工作大鼠心脏中，研究了生理雌激素水平（皮克）对缺血后心肌功能的作用，实验分为无预处理组（n = 28，实验1）和有预处理组（n = 15，实验2）。对于实验1，雌性去卵巢大鼠接受安慰剂治疗（n = 19）或17β - 雌二醇（E2，n = 9；慢性E2），14天后取出心脏并在体外用改良的克雷布斯 - 亨泽莱特缓冲液灌注。在9只接受安慰剂治疗的大鼠中，在缺血前20分钟给予E2（急性E2）。心脏经历15分钟的全心缺血和20分钟的再灌注。在实验2中，去卵巢大鼠接受安慰剂治疗（n = 8）或17β - E2（慢性E2，n = 7）。在该实验中，心脏先进行预处理，然后经历20分钟的持续缺血，随后是20分钟的再灌注。通过夹闭主动脉并限制左心房血流使冠状动脉血流降至零来产生全心缺血；在整个研究过程中持续监测血流动力学。在基线、缺血期末和再灌注期间评估主动脉血流、冠状动脉血流、心输出量和dP/dt。通过缺血后乳酸、乳酸脱氢酶和肌酸激酶的释放来测量缺血的严重程度，在每项研究的所有组中相似。在实验1中，慢性E2治疗的大鼠在再灌注后主动脉血流、心输出量和dP/dt的恢复显著改善（P<0.05）；急性E2没有显著益处。缺血后冠状动脉血流的恢复没有受到显著影响。在实验2中，与对照组相比，慢性E2治疗也显著改善了预处理心脏缺血后的心脏功能恢复（P<0.05）。总之，去卵巢大鼠中E2替代改善了全心缺血和再灌注后的收缩功能；观察到雌激素的心脏保护作用超过了缺血预处理所赋予的保护作用。由于E2的心脏保护作用与冠状动脉血流的显著改善无关，推测该激素对心肌细胞有直接作用。
