McDonald K M, Rector T, Carlyle P F, Francis G S, Cohn J N
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
J Am Coll Cardiol. 1994 Dec;24(7):1762-8. doi: 10.1016/0735-1097(94)90185-6.
This study was designed to assess the effect of angiotensin-converting enzyme inhibition and beta-adrenoreceptor blockade on established ventricular remodeling.
Angiotensin-converting enzyme inhibitor therapy attenuates the development of ventricular remodeling when given shortly after myocardial infarction. However, regression of established ventricular remodeling after infarction has received little attention.
The relative effects of angiotensin-converting enzyme inhibitor therapy and beta-adrenoceptor blockade on established ventricular remodeling were assessed in a canine model characterized by increased left ventricular mass and chamber dilation as a result of localized myocardial necrosis produced by transmyocardial direct current shock. Dogs were randomly assigned to 3 months of therapy with captopril (25 mg twice daily, n = 7) or metoprolol (100 mg twice daily, n = 7) or to a control group with no intervention (n = 6), 11 +/- 4 (mean +/- SD) months after acute myocardial damage.
Compared with the control group, dogs in both the captopril and metoprolol groups had reduced left ventricular mass as measured by magnetic resonance imaging (-8.1 +/- 3.8 vs. 1.7 +/- 2.8 g, p = 0.003 and -9.6 +/- 5.6 vs. 1.7 +/- 2.8 g, p = 0.001), respectively. Captopril and metoprolol also produced a reduction in left ventricular end-diastolic volume (-7.6 +/- 6.0 and -6.0 +/- 5.8 ml, respectively) compared with the control value (-1.6 +/- 3.8 ml) (p = 0.14 [NS]). Both agents reduced mean arterial pressure but had disparate effects on pulmonary wedge pressure and right atrial pressure. There was no significant correlation between change in ventricular mass or volume and change in any measured hemodynamic or neurohormonal variable.
These data suggest that pharmacologic intervention with angiotensin-converting enzyme inhibition or beta-adrenoceptor blockade can result in regression of established ventricular remodeling. The mechanism of this response will require further study, but these data did not support a close association between regression of remodeling and hemodynamic unloading of the ventricle or systemic neuroendocrine factors.
本研究旨在评估血管紧张素转换酶抑制和β-肾上腺素能受体阻滞对已发生的心室重构的影响。
血管紧张素转换酶抑制剂治疗在心肌梗死后短期内应用可减轻心室重构的发展。然而，梗死发生后已形成的心室重构的逆转很少受到关注。
在一个犬类模型中评估血管紧张素转换酶抑制剂治疗和β-肾上腺素能受体阻滞对已发生的心室重构的相对作用，该模型的特征是由于经心肌直流电休克导致局部心肌坏死而出现左心室质量增加和心腔扩张。在急性心肌损伤后11±4（平均±标准差）个月，将犬随机分为三组，分别接受卡托普利治疗3个月（25mg，每日两次，n = 7）、美托洛尔治疗3个月（100mg，每日两次，n = 7）或不进行干预的对照组（n = 6）。
与对照组相比，卡托普利组和美托洛尔组犬经磁共振成像测量的左心室质量均降低（分别为-8.1±3.8 vs. 1.7±2.8g，p = 0.003和-9.6±5.6 vs. 1.7±2.8g，p = 0.001）。与对照值（-1.6±3.8ml）相比，卡托普利和美托洛尔还使左心室舒张末期容积减少（分别为-7.6±6.0和-6.0±5.8ml）（p = 0.14[无显著性差异]）。两种药物均降低平均动脉压，但对肺楔压和右心房压有不同影响。心室质量或容积的变化与任何测量的血流动力学或神经激素变量的变化之间无显著相关性。
这些数据表明，血管紧张素转换酶抑制或β-肾上腺素能受体阻滞的药物干预可导致已发生的心室重构逆转。这种反应的机制需要进一步研究，但这些数据不支持重构逆转与心室血流动力学负荷减轻或全身神经内分泌因素之间存在密切关联。
