NITRENDIPINE BINDING IN CONGESTIVE HEART-FAILURE DUE TO MYOCARDIAL-INFARCTION
NITRENDIPINE BINDING IN CONGESTIVE HEART-FAILURE DUE TO MYOCARDIAL-INFARCTION
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DOI：
10.1161/01.res.66.3.782
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发表时间：
1990-03-01
影响因子：
20.1
通讯作者：
DHALLA, NS
中科院分区：
文献类型：
--
作者：
DIXON, IMC;LEE, SL;DHALLA, NS
心泵功能低下是充血性心力衰竭的标志，推测心肌细胞内钙离子内流减少是导致心脏收缩功能低下的原因。由于肌膜上的钙通道被认为是钙离子进入的重要途径，我们研究了左心室游离壁心肌梗死后衰竭大鼠心脏的钙受体/通道的状态。为此，结扎左冠状动脉，并在4、8和16周后检查心脏；假手术动物作为对照。血流动力学评估显示总机械能(左心室收缩压)下降。4周、8周和16周时，实验动物的左心室舒张压升高，正、负dp/dt降低。虽然腹水在4周时明显积聚，但实验大鼠心力衰竭的其他临床症状在诱导心肌梗死后8周和16周出现肺充血和心脏扩张。用[~3H]尼群地平结合试验测定，实验8周和16周非梗死组大鼠左室壁钙离子受体/通道密度降低，但尼群地平的亲和力无明显变化。在另一种二氢吡啶化合物[~3H]PN200-110的特定结合中，类似的抑制作用在衰竭的心脏中也很明显。与右心室和肝脏不同的是，脑和骨骼肌粗膜标本显示实验动物16周时钙离子受体/通道密度下降。16周时，衰竭动物的心脏匀浆和纯化的肌膜制剂中也出现了钙通道数量的减少。这些数据支持这样一种观点，即在中到重度充血性心力衰竭阶段，心肌钙离子进入的调控机制可能被抑制，这种变化可能是充血性心力衰竭发展过程中发生的事件的结果。
Depressed cardiac pump function is the hallmark of congestive heart failure, and it is suspected that decreased influx of Ca2+ into the cardiac cell is responsible for depressed contractile function. Since Ca2+ channels in the sarcolemmal membrane are considered to be an important route for the entry of Ca2+, we examined the status of Ca2+ receptors/channels in failing rat hearts after myocardial infarction of the left ventricular free wall. For this purpose, the left coronary artery was ligated and hearts were examined 4,8, and 16 weeks later; sham-operated animals served as controls. Hemodynamic assessment revealed decreased total mechanical energy (left ventricular systolic pressure .times. heart rate), increased left ventricular diastolic pressure, and decreased positive and negative dP/dt in experimental animals at 4,8, and 16 weeks. Although accumulation of ascites in the abdominal cavity was evident at 4 weeks, other clinical signs of congestive heart failure in experimental rats were evident from the presence of lung congestion and cardiac dilatation at 8 and 16 weeks after induction of myocardial infarction. The density of Ca2+ receptors/channels in crude membranes, as assessed by [3H]nitrendipine binding assay, was found to be decreased in the uninfarcted experimental left ventricle at 8 and 16 weeks; however, no change in the affinity of nitrendipine was evident. A similar depression in the specific binding of another dihydropyridine compound, [3H]PN200-110, was also evident in failing hearts. Brain and skeletal muscle crude membrane preparations, unlike those of the right ventricle and liver, revealed a decrease in Ca2+ receptors/channels density in experimental animals at 16 weeks. Reduction in the Ca2+ channel number was also seen in heart homogenate as well as purified sarcolemmal preparations from failing animals at 16 weeks. These data support the view that mechanisms governing the entry of Ca2+ in the myocardium may be depressed in moderate to severe stages of congestive heart failure, and such changes may be a consequence of events occurring during the development of congestive heart failure.