Mulder P, Devaux B, Richard V, Henry J P, Wimart M C, Thibout E, Macé B, Thuillez C
Department of Pharmacology, VACOMED, IFRMP 23, Rouen University Medical School, France.
Circulation. 1997 Mar 4;95(5):1314-9. doi: 10.1161/01.cir.95.5.1314.
The efficacy of ACE inhibitors in congestive heart failure (CHF) might be affected by the pathophysiological status present at the onset of treatment. We compared in a rat model the effects of ACE inhibition (lisinopril, 10 mg.kg-1.d-1) initiated early (1 week) or late (3 months) after myocardial infarction (i.e., at time points corresponding to moderate or severe CHF without or with established cardiac remodeling).
Survival was improved by early treatment at 3 months (from 76% to 95%) and by both early and delayed treatment at 9 months (placebo, 28%; early, 90%; delayed, 61%). Delayed treatment was initiated in a more severe pathophysiological context of CHF than early treatment, illustrated in untreated rats by higher left ventricular (LV) end-diastolic and central venous pressures and by increased LV weight and LV cavity circumference. After 9 months, early and delayed treatments reduced systolic, LV end-diastolic, and central venous pressures. Both treatments also similarly decreased LV weight, LV cavity circumference, and LV collagen density.
In this rat model of CHF, early and delayed ACE inhibitor treatments both increase survival and exert similar beneficial effects on cardiac hemodynamics and remodeling. Although early treatment prevents the development of ventricular dysfunction and remodeling, delayed treatment is capable of reversing cardiac hypertrophy and remodeling, as well as ventricular dysfunction. Thus, ACE inhibitors exert marked beneficial effects even when treatment is initiated late into the evolution of heart failure (ie, at a time of established ventricular dysfunction and remodeling).
血管紧张素转换酶（ACE）抑制剂在充血性心力衰竭（CHF）中的疗效可能受治疗开始时病理生理状态的影响。我们在大鼠模型中比较了心肌梗死后早期（1周）或晚期（3个月）开始使用ACE抑制剂（赖诺普利，10mg·kg⁻¹·d⁻¹）的效果（即对应于无心脏重构或有已确立心脏重构的中度或重度CHF的时间点）。
3个月时早期治疗可提高生存率（从76%提高到95%），9个月时早期和延迟治疗均可提高生存率（安慰剂组为28%；早期治疗组为90%；延迟治疗组为61%）。延迟治疗开始时的CHF病理生理状态比早期治疗时更严重，在未治疗的大鼠中表现为更高的左心室（LV）舒张末期压力和中心静脉压，以及LV重量增加和LV腔周长增加。9个月后，早期和延迟治疗均降低了收缩压、LV舒张末期压力和中心静脉压。两种治疗还同样降低了LV重量、LV腔周长和LV胶原密度。
在这个CHF大鼠模型中，早期和延迟使用ACE抑制剂治疗均可提高生存率，并对心脏血流动力学和重构产生相似的有益作用。尽管早期治疗可预防心室功能障碍和重构的发生，但延迟治疗能够逆转心脏肥大和重构以及心室功能障碍。因此，即使在心力衰竭进展后期开始治疗（即心室功能障碍和重构已确立时），ACE抑制剂仍可发挥显著的有益作用。
