Allard M F, Flint J D, English J C, Henning S L, Salamanca M C, Kamimura C T, English D R
Cardiovascular Research Laboratory, St. Paul's Hospital, Vancouver, BC, Canada.
J Mol Cell Cardiol. 1994 Dec;26(12):1551-63. doi: 10.1006/jmcc.1994.1175.
In this study, calcium overload during reperfusion and the severity of morphologically evident ischemic myocardial injury were compared in hypertrophied and normal hearts. Hypertrophied hearts isolated from rats where a clip had been placed on the proximal thoracic aorta for 6 weeks were compared to those from sham-operated rats in an isolated state perfused with Krebs-Henseleit buffer containing 3% albumin, 1.2 mM palmitate and 11 mM glucose. The isolated hearts were exposed to global, no-flow, normothermic ischemia following potassium arrest and were reperfused. Following ischemia and reperfusion, left ventricular end diastolic pressure was increased (39 +/- 7 v 13 +/- 2 mmHg, P < 0.05), and percentage recovery of left ventricular systolic function was decreased (34.4 +/- 8.9 v 77.1 +/- 6.3% P < 0.05), in hypertrophied hearts compared to control hearts. Calcium overload during reperfusion was two and one-half times greater in the hypertrophied hearts than in the control hearts and showed significant relationships with recovery of left ventricular systolic function (r = -0.86, P < 0.001) and left ventricular end diastolic pressure (r = 0.78, P < 0.005). Myocardial energy charge did not differ between the two groups at the end of reperfusion. Ischemic myocardial injury was quantitated morphologically by point counting techniques in a comparable series of control and hypertrophied hearts. After ischemia, hearts were either exposed to a monoclonal antimyosin antibody to identify and measure irreversibly injured myocardium by light microscopy or fixed by perfusion with 2.5% glutaraldehyde to quantitate the morphologic changes ultrastructurally. Control and hypertrophied hearts were not significantly different in severity of myocardial injury due to ischemia as assessed morphologically. Thus, the data suggest that calcium overload during reperfusion plays a significant role in post-ischemic left ventricular dysfunction of the hypertrophied heart. The accelerated calcium overload that occurs in the hypertrophied rat heart during reperfusion cannot be explained by differences in severity of myocardial injury during ischemia which indicates that other mechanisms are responsible.
在本研究中，对肥厚心脏和正常心脏再灌注期间的钙超载情况以及形态学上明显的缺血性心肌损伤的严重程度进行了比较。将从大鼠身上分离出的肥厚心脏（这些大鼠的胸主动脉近端已放置夹子6周）与假手术大鼠的心脏进行比较，所有心脏均在离体状态下用含有3%白蛋白、1.2 mM棕榈酸盐和11 mM葡萄糖的克雷布斯 - 亨泽莱特缓冲液灌注。将离体心脏在钾停搏后进行全心、无血流、常温缺血处理，然后再灌注。缺血和再灌注后，与对照心脏相比，肥厚心脏的左心室舒张末期压力升高（39±7对13±2 mmHg，P<0.05），左心室收缩功能的恢复百分比降低（34.4±8.9对77.1±6.3%，P<0.05）。肥厚心脏再灌注期间的钙超载比对照心脏大2.5倍，并且与左心室收缩功能的恢复（r = -0.86，P<0.001）和左心室舒张末期压力（r = 0.78，P<0.005）呈显著相关。再灌注结束时，两组之间的心肌能荷没有差异。通过点计数技术在一系列可比的对照和肥厚心脏中对缺血性心肌损伤进行形态学定量。缺血后，心脏要么暴露于单克隆抗肌球蛋白抗体，通过光学显微镜识别和测量不可逆损伤的心肌，要么用2.5%戊二醛灌注固定以超微结构定量形态学变化。从形态学评估来看，对照心脏和肥厚心脏因缺血导致心肌损伤的严重程度没有显著差异。因此，数据表明再灌注期间的钙超载在肥厚心脏缺血后左心室功能障碍中起重要作用。肥厚大鼠心脏在再灌注期间发生的加速钙超载不能用缺血期间心肌损伤严重程度的差异来解释，这表明还有其他机制在起作用。
