Decreased energy reserve in an animal model of dilated cardiomyopathy - Relationship to contractile performance
Decreased energy reserve in an animal model of dilated cardiomyopathy - Relationship to contractile performance
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DOI：
10.1161/01.res.78.5.893
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发表时间：
1996-05-01
影响因子：
20.1
通讯作者：
Ingwall, JS
中科院分区：
文献类型：
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作者：
Liao, RL;Nascimben, L;Ingwall, JS
使用动物模型来检验以下假设：在心力衰竭中，通过肌酸激酶（CK）反应（我们称之为能量储备）再合成ATP的能力降低导致心脏无法维持其正常功能和收缩储备。用呋喃唑酮喂养1周龄火鸡幼雏14天，诱导扩张型心肌病。从这些肌病动物中分离的Langendorff灌注心脏显示基线等容收缩性能降低73%。增加[Ca ~（2+）]（o）和电起搏频率均不增加等容收缩性能。P-31核磁共振磁化转移和化学分析测定，ATP浓度降低23%，磷酸肌酸浓度降低42%，CK酶活性降低34%，CK反应的假一级速率常数降低50%。测得的CK反应速度下降了71%。在CK反应速度较低的心脏中，增加[Ca 2 +]（o）增加心脏性能的能力降低，部分通过喂食单独一组火鸡幼雏β-胍基丙酸来重现，以通过降低胍基底物浓度来特异性降低CK反应速度。这些心脏具有正常的基线性能，但收缩储备减弱。这些观察结果为以下假设提供了进一步的支持：通过CK系统的能量储备减少有助于衰竭心脏的心脏功能降低。
An animal model was used to test the hypothesis that in heart failure the decrease in the ability to resynthesize ATP through the creatine kinase (CK) reaction (which we call energy reserve) contributes to the inability of the heart to maintain its normal function and contractile reserve. One week-old turkey poults were fed furazolidone for 14 days to induce dilated cardiomyopathy. Isolated Langendorff-perfused hearts from these myopathic animals showed a 73% decrease in baseline isovolumic contractile performance. Neither increasing [Ca2+](o) nor electrical pacing rate increased isovolumic contractile performance, Measured by P-31 nuclear magnetic resonance magnetization transfer and chemical assay, ATP concentration was decreased by 23%, phosphocreatine concentration by 42%, CK enzyme activity by 34%, and the pseudo first-order rate constant for the CK reaction by 50%. Measured CK reaction velocity decreased by 71%. The reduced ability to increase cardiac performance in response to increasing [Ca2+](o) in hearts with lower CK reaction velocity was reproduced in part by feeding a separate group of turkey poults beta-guanidinopropionic acid to specifically reduce CK reaction velocity by decreasing guanidino substrate concentration. These hearts had normal baseline performance but blunted contractile re serve. These observations provide further support for the hypothesis that a decrease in energy reserve via the CK system contributes to reduced cardiac function in the failing heart.