INHIBITION OF THE CREATINE-KINASE REACTION DECREASES THE CONTRACTILE RESERVE OF ISOLATED RAT HEARTS
INHIBITION OF THE CREATINE-KINASE REACTION DECREASES THE CONTRACTILE RESERVE OF ISOLATED RAT HEARTS
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DOI：
10.1152/ajpheart.1995.269.3.h1030
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发表时间：
1995-09-01
影响因子：
4.8
通讯作者：
INGWALL, JS
中科院分区：
文献类型：
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作者：
HAMMAN, BL;BITTL, JA;INGWALL, JS
为了确定磷酸转移通过肌酸激酶（CK）和完整的跳动的心脏做工作的能力之间的关系，我们化学抑制CK的活性，然后测量在生理和急性应激条件下的心脏性能。离体灌注大鼠心脏暴露于碘乙酰胺（IA），并进行三种心脏应激之一：高钙（Ca 2 + = 3 mM）缓冲液灌注（n = 7），去甲肾上腺素（2 μ mol/min）输注（n = 6），或缺氧缓冲液灌注（n = 5）。IA降低CK活性至接近零，测量在完整的心脏P-31磁化转移，和2%的控制CK活性，测量在心肌匀浆。CK同工酶谱无变化，表明所有同工酶的非选择性IA抑制。从IA处理的心脏中分离的线粒体具有正常的ADP：O比率，状态3呼吸速率，和不变的受体和呼吸控制比率。肌动球蛋白腺苷三磷酸酶和腺苷酸激酶活性均未改变。IA暴露后，舒张末期压，左心室发展的压力，和心率不变，至少30分钟，在生理灌注压，但在应力条件下观察到大的变化。高钙灌注和去甲肾上腺素输注引起的左心室发展压升高分别降低了39%和54%。在缺氧过程中，磷酸肌酸消耗率降低了57%，左心室发展压力下降，舒张末期压增加速度比对照组快。这些结果表明，通过IA将CK抑制至对照活性的< 2%使收缩储备减少了约50%。我们得出结论，CK活性是必不可少的表达的全动态范围的心肌性能。
To define the relation between phosphoryl transfer via creatine kinase (CK) and the ability of the intact beating heart to do work, we chemically inhibited CK activity and then measured cardiac performance under physiological and acute stress conditions. Isolated perfused rat hearts were exposed to iodoacetamide (IA) and subjected to one of three cardiac stresses: hypercalcemic (Ca2+ = 3 mM) buffer perfusion (n = 7), norepinephrine (2 mu mol/min) infusion (n = 6), or hypoxic buffer perfusion (n = 5). IA decreased CK activity to near zero, measured in intact hearts by P-31 magnetization transfer, and to 2% of control CK activity, measured in myocardial homogenates. The CK isoenzyme profile was unchanged, suggesting nonselective IA inhibition of all isoenzymes. Mitochondria isolated from IA-treated hearts had normal ADP:O ratios, state 3 respiratory rates, and unchanged acceptor and respiratory control ratios. Neither actomyosin adenosinetriphosphatase nor adenylate kinase activities were changed. After IA exposure, end-diastolic pressure, left ventricular developed pressure, and heart rate were unchanged for at least 30 min at physiological perfusion pressures, but large changes were observed during stress conditions. The increase in left ventricular developed pressure induced by hypercalcemic perfusion and by norepinephrine infusion decreased by 39 and 54%, respectively. During hypoxia, the rate of phosphocreatine depletion was decreased by 57%, left ventricular developed pressure declined, and end-diastolic pressure increased faster than in controls. These results show that inhibition of CK to < 2% of control activity by IA reduced contractile reserve by similar to 50%. We conclude that CK activity is essential for the expression of the full dynamic range of myocardial performance.