Sanbe A, Tanonaka K, Hanaoka Y, Katoh T, Takeo S
Department of Pharmacology, Tokyo College of Pharmacy, Japan.
J Mol Cell Cardiol. 1993 Sep;25(9):995-1013. doi: 10.1006/jmcc.1993.1113.
To elucidate the relationship between functional alterations and disturbances in myocardial energy metabolism of rats with heart failure following coronary artery ligation, the left coronary artery of the rat was ligated and the time course of changes in cardiac function and myocardial energy state of the animal were examined for 12 weeks after the ligation. Coronary artery ligation resulted in approximately 40% infarction of the left ventricle, an increase in the right ventricular weight, a decrease in left ventricular developed pressure, an increase in left ventricular end-diastolic pressure throughout the experiment, suggesting the development of cardiac failure after the operation. Cardiac output and stroke volume indices were not altered during the first 4 weeks, but were significantly decreased on the 8th and 12th weeks, suggesting that cardiac function had further aggravated by 8 weeks after the operation. Myocardial energy profiles of the scar tissue, the remaining left ventricle and interseptum, and the right ventricle were determined. Tissue ATP (27.54 +/- 0.82 to 26.38 +/- 1.58 mumol/g dry tissue; n = 8-10) and creatine phosphate (26.73 +/- 1.63 to 24.38 +/- 1.83 mumol/g dry tissue; n = 8-10) of the remaining viable left ventricle were lower than control (33.17 +/- 0.73 and 40.04 +/- 1.07 mumol/g dry tissue; n = 8) throughout the experiment. A marked decrease in tissue ATP and CP was seen in the scar tissue throughout the experiment. Increases in tissue lactate of the remaining left ventricle and the right ventricle were detected from 1 to 2 weeks after the operation, but returned to the control levels thereafter. Mitochondrial oxygen consumption rates of isolated myocardial bundles from the 8th and 12th weeks (21.03 +/- 2.22 and 17.79 +/- 3.24 ng oxygen/min/mg dry tissue; n = 8) were lower than control (33.15 +/- 1.95 ng oxygen/min/mg dry tissue; n = 5), and those of the interseptum (23.71 +/- 1.33 ng oxygen/min/mg dry tissue; n = 8) and the right ventricle (22.44 +/- 2.73 ng oxygen/min/mg dry tissue; n = 8) on the 12th week after the operation were lower than control (33.58 +/- 2.80 and 34.83 +/- 2.64 ng oxygen/min/mg dry tissue; n = 5). The results provide evidence for a decline in myocardial energy store and energy producing ability associated with the development of cardiac failure.
为阐明冠状动脉结扎所致心力衰竭大鼠心肌能量代谢紊乱与功能改变之间的关系，结扎大鼠左冠状动脉，并在结扎后12周观察动物心脏功能和心肌能量状态的时间变化过程。冠状动脉结扎导致左心室约40%梗死，右心室重量增加，左心室舒张末压降低，实验全程左心室舒张末压升高，提示术后发生心力衰竭。心输出量和每搏量指数在最初4周未改变，但在第8周和第12周显著降低，提示术后8周心脏功能进一步恶化。测定瘢痕组织、剩余左心室和室间隔以及右心室的心肌能量谱。实验全程，剩余存活左心室的组织ATP（27.54±0.82至26.38±1.58μmol/g干组织；n = 8 - 10）和磷酸肌酸（26.73±1.63至24.38±1.83μmol/g干组织；n = 8 - 10）均低于对照组（33.17±0.73和40.04±1.07μmol/g干组织；n = 8）。实验全程瘢痕组织中组织ATP和CP显著降低。术后1至2周检测到剩余左心室和右心室组织乳酸增加，但此后恢复至对照水平。第8周和第12周分离的心肌束线粒体氧消耗率（21.03±2.22和17.79±3.24 ng氧/min/mg干组织；n = 8）低于对照组（33.15±1.95 ng氧/min/mg干组织；n = 5），术后第12周室间隔（23.71±1.33 ng氧/min/mg干组织；n = 8）和右心室（22.44±2.73 ng氧/min/mg干组织；n = 8）的线粒体氧消耗率低于对照组（33.58±2.80和34.83±2.64 ng氧/min/mg干组织；n = 5）。这些结果为心力衰竭发展过程中心肌能量储备和能量产生能力下降提供了证据。
