CONTRACTILITY AND STIFFNESS OF NONINFARCTED MYOCARDIUM AFTER CORONARY LIGATION IN RATS - EFFECTS OF CHRONIC ANGIOTENSIN CONVERTING ENZYME-INHIBITION
CONTRACTILITY AND STIFFNESS OF NONINFARCTED MYOCARDIUM AFTER CORONARY LIGATION IN RATS - EFFECTS OF CHRONIC ANGIOTENSIN CONVERTING ENZYME-INHIBITION
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DOI：
10.1161/01.cir.83.3.1028
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发表时间：
1991-03-01
期刊：
影响因子：
37.8
通讯作者：
GOLDMAN, S
中科院分区：
文献类型：
--
作者：
LITWIN, SE;LITWIN, CM;GOLDMAN, S
背景既往研究表明，心肌梗死后左室整体功能下降。然而，关于心肌梗死对残余心肌的收缩性和被动弹性的影响知之甚少。我们评估了假手术或心肌梗死后6周大鼠离体非梗死左心室乳头肌的等长功能和被动心肌硬度。与对照组相比，未治疗的大面积心肌梗死大鼠的最大发展张力和张力升高峰值速率（+dT/dt）显著降低（分别为3.3 +/- 1.1 vs 4.3 +/- 0.6 g/mm 2和49.5 +/- 17.5 vs 72.5 +/- 10.5 g/mm 2/sec）。与对照组相比，未治疗的心肌梗死大鼠达到峰值张力的时间延长（120 +/- 8对102 +/- 4毫秒），心肌硬度增加（35.2 +/- 4.9对24.2 +/- 3.7）。心肌梗死面积较小的大鼠与对照组的差异仅在于达到峰值张力的时间延长。与对照组相比，大面积心肌梗死大鼠乳头肌细胞横截面积增加44%（p < 0.05），心肌羟脯氨酸含量增加160%（p < 0.05）。为了确定心肌梗死后改善左心室功能的治疗是否也改善心肌功能，在心肌梗死后3周开始用卡托普利治疗大鼠并持续3周。在心肌梗死大鼠中，用卡托普利治疗减弱了达到峰值张力时间的延长;然而，发展的张力、+dT/dt和肌肉僵硬度仍然异常。与未治疗的心肌梗死大鼠相比，卡托普利治疗的心肌梗死大鼠的心肌细胞横截面积减少了9%（p = 0.1），但心肌胶原蛋白含量持续增加。总之，大鼠大面积心肌梗死导致收缩功能障碍、僵硬度增加、肌细胞肥大和残留非梗死心肌中胶原含量增加。卡托普利治疗改变了心脏重塑和肥厚的过程，并改善了非梗死心肌收缩力的一个参数;然而，心肌胶原含量和心肌硬度仍然异常。这些结果表明，血管紧张素转换酶抑制剂在大鼠心肌梗死模型的心力衰竭改善全球心脏性能通过对心肌功能和外周循环的综合作用。
Background. Previous studies have shown that global left ventricular function is depressed after myocardial infarction. However, little is known about the effects of myocardial infarction on contractility and the passive-elastic properties of residual myocardium.Methods and Results. We evaluated isometric function and passive myocardial stiffness in isolated, noninfarcted left ventricular papillary muscle from rats 6 weeks after sham operation or myocardial infarction. Maximal developed tension and peak rate of tension rise (+dT/dt) were significantly decreased in untreated rats with large myocardial infarction compared with controls (3.3 +/- 1.1 versus 4.3 +/- 0.6 g/mm2 and 49.5 +/- 17.5 versus 72.5 +/- 10.5 g/mm2/sec, respectively). Time to peak tension was prolonged (120 +/- 8 versus 102 +/- 4 msec) and myocardial stiffness was increased in untreated myocardial infarction rats compared with controls (35.2 +/- 4.9 versus 24.2 +/- 3.7). Rats with smaller myocardial infarctions differed from controls only with respect to a prolongation of time to peak tension. Papillary muscle myocyte cross-sectional area was increased by 44% (p < 0.05), and myocardial hydroxyproline content was increased by 160% (p < 0.05) in rats with large myocardial infarctions compared with controls. To determine whether treatment that improves left ventricular function after myocardial infarction also improves myocardial function, rats were treated with captopril beginning 3 weeks after myocardial infarction and continuing for 3 weeks. Treatment with captopril attenuated the prolongation in time to peak tension in the myocardial infarction rats; however, developed tension, +dT/dt, and muscle stiffness remained abnormal. Compared with untreated myocardial infarction rats, captopril-treated myocardial infarction rats had a 9% decrease in myocyte cross-sectional area (p = 0.1) but a persistent increase in myocardial collagen content. In summary, large myocardial infarction in rats causes contractile dysfunction, increased stiffness, myocyte hypertrophy, and increased collagen content in the residual noninfarcted myocardium. Treatment with captopril alters the process of cardiac remodeling and hypertrophy and improves one parameter of contractility in noninfarcted myocardium; however, myocardial collagen content and myocardial stiffness remain abnormal.Conclusions. These findings suggest that angiotensin converting enzyme inhibition in the rat infarct model of heart failure improves global cardiac performance via combined effects on myocardial function and the peripheral circulation.