Progressive cardiac dysfunction and fibrosis in the cardiomyopathic hamster and effects of growth hormone and angiotensin-converting enzyme inhibition.
Progressive cardiac dysfunction and fibrosis in the cardiomyopathic hamster and effects of growth hormone and angiotensin-converting enzyme inhibition.
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DOI：
10.1161/01.cir.100.16.1734
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发表时间：
1999-10
期刊：
影响因子：
37.8
通讯作者：
T. Ryoke;Yusu Gu;L. Mao;M. Hongo;R. Clark;Kirk L. Peterson;J. Ross
中科院分区：
文献类型：
--
作者：
T. Ryoke;Yusu Gu;L. Mao;M. Hongo;R. Clark;Kirk L. Peterson;J. Ross
背景生长激素（GH）可改善心肌梗塞大鼠的心功能，但其在原发性扩张型心肌病模型中的作用尚未见报道。在心肌病 (CM) 仓鼠的疾病早期（4 个月）和晚期（10 个月）阶段检查 GH 的作用，并在晚期心力衰竭中评估 GH 与慢性 ACE 抑制的组合。方法和结果 CM 仓鼠（CHF 147 系）在 4 个月时表现出严重的左心室（LV）收缩功能障碍，而左心室充盈压正常；在 10 个月时，随着心肌纤维化的加剧，出现更严重的收缩和舒张功能障碍。 4 个月时单独使用重组人 GH 3 周可增加左室壁厚度并降低收缩期壁应力，但不会改变舒张期壁应力，而在 10 个月时，壁应力和缩短分数没有改善。 GH 在两个年龄段的 LV dP/dt(max) 均得到增强，4 个月时反映收缩力增加，但 10 个月时最有可能是由于 LV 充盈压升高所致。纤维化程度的增加与左心室功能呈负相关，但不受生长激素的影响。在其他 CM 仓鼠中，单独使用高剂量 ACE 抑制剂（喹那普利），从 8 个月开始并持续 11 周，改善了左室功能并抑制了不利的重塑，但在 10 个月大时添加 GH 3 周，导致室壁厚度增加，几乎没有额外的功能益处，并增加了左室充盈压和舒张期壁应力。结论 单独使用 GH 治疗可以通过增加收缩力和减少室壁应力来改善 4 个月大的 CM 仓鼠的左心室功能障碍，但在 10 个月大时对严重的左心衰竭几乎没有有益效果。慢性 ACE 抑制后，10 个月时添加 GH 没有额外的有益作用，并且进一步增加了左心室舒张压。 GH 的这些不同作用可能与 CM 仓鼠的 LV 纤维化逐渐增加有关。
BACKGROUND Growth hormone (GH) improves cardiac function in the rat with myocardial infarction, but its effects in a model of primary dilated cardiomyopathy have not been reported. GH effects were examined at early (4 months) and late (10 months) phases of disease in the cardiomyopathic (CM) hamster, and the combination of GH with chronic ACE inhibition was assessed in late-phase heart failure. METHODS AND RESULTS CM hamsters (CHF 147 line) at 4 months showed severe systolic left ventricular (LV) dysfunction with normal LV filling pressure, and at 10 months there was more severe systolic as well as diastolic dysfunction with increasing myocardial fibrosis. Recombinant human GH alone for 3 weeks at age 4 months increased LV wall thickness and reduced systolic wall stress without altering diastolic wall stress, whereas at 10 months, wall stress and fractional shortening did not improve. The LV dP/dt(max) was enhanced at both ages by GH, which at 4 months reflected increased contractility, but at 10 months was most likely caused by elevation of the LV filling pressure. The increasing degree of fibrosis correlated inversely with LV function but was unaffected by GH. In other CM hamsters, high-dose ACE inhibition alone (quinapril), started at 8 months and continued for 11 weeks, improved LV function and inhibited unfavorable remodeling, but the addition of GH for 3 weeks at age 10 months produced increased wall thickness with little additional functional benefit and increased the LV filling pressure and diastolic wall stress. CONCLUSIONS GH treatment alone improved LV dysfunction at 4 months of age in CM hamsters by increasing contractility and reducing wall stress but had few beneficial effects at 10 months in severe LV failure. After chronic ACE inhibition, addition of GH at 10 months had no additional beneficial effects and further increased LV diastolic pressure. These differing effects of GH may relate to the progressive increase of LV fibrosis in the CM hamster.