Progressive loss of myocardial ATP due to a loss of total purines during the development of heart failure in dogs - A compensatory role for the parallel loss of creatine

Progressive loss of myocardial ATP due to a loss of total purines during the development of heart failure in dogs - A compensatory role for the parallel loss of creatine
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DOI:
10.1161/01.cir.100.20.2113
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发表时间:
1999-11-16
期刊:
影响因子:
37.8
通讯作者:
Ingwall, JS
Ingwall, JS
中科院分区:
医学1区
文献类型:
--
作者:
Shen, WQ;Asai, K;Ingwall, JS

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心力衰竭时心肌ATP含量是否福尔斯是一个长期存在且有争议的问题。机制(S),以解释任何减少ATP含量在heart failure.Methods和Results-Cardiac功能障碍,心力衰竭,心力衰竭和一个长期的稳定状态的心力衰竭诱导慢性右心室起搏1至2周,3至4周,7至9周的狗。在清醒状态下测定心功能和心肌耗氧量(MVo(2))。ATP,总嘌呤,肌酸在每个阶段获得的活检标本进行测量。ATP和总嘌呤池以0.12和0.15 nmol mg蛋白(-1).d(-1)的速率逐渐下降,尽管MVo增加(2)。肌酸的损失率为1.06nmol·mg蛋白(-1)·d(-1),比总嘌呤的消耗快7倍。(2)肌酸的丢失是心力衰竭的早期标志,可能是一种代偿机制,使衰竭心脏中总嘌呤池的减少最小化。
Background-Whether myocardial ATP content falls in heart failure is a long-standing and controversial issue. The mechanism(s) to explain any decrease in ATP content during heart failure have not been identified.Methods and Results-Cardiac dysfunction, heart failure, and a prolonged steady state of heart failure were induced by chronic right ventricular pacing for 1 to 2 weeks, 3 to 4 weeks, and 7 to 9 weeks in dogs. Cardiac function and myocardial O-2 consumption (MVo(2)) were measured with the dogs in the conscious state. ATP, total purine, and creatine were measured in biopsy specimens obtained at each stage. ATP and the total purine pool progressively fell at rates of 0.12 and 0.15 nmol mg protein(-1).d(-1), despite an increase in MVo(2). The rate of loss of creatine was 1.06 nmol mg protein(-1).d(-1), 7 times faster than the depletion of total purine.Conclusions-(1) ATP contents progressively decreased during heart failure as a result of a loss of the total purine pool. The loss of purines may be due to inhibition of de novo purine synthesis, (2) Loss of creatine is an early marker of heart failure and mmay serve as a compensatory mechanism minimizing the reduction of the total purine pool in the failing heart.