Oral administration of donepezil, a centrally acting acetylcholinesterase inhibitor, improves the survival of rats with chronic heart failure (CHF). The mechanisms of cardioprotective effects of donepezil, however, remain totally unknown. To elucidate potential mechanisms, we examined whether central microinfusion of donepezil would exert cardioprotection. Intracerebroventricular microinfusion pumps with cerebroventricular cannula were implanted in rats with myocardial infarction. The rats were randomly divided into central saline treatment (CST) and central donepezil treatment (CDT) groups. We evaluated cardiac remodeling and function after a 6-week treatment and examined the 160-day survival rate. Compared to the CST, the CDT markedly improved the 160-day survival rate (68% vs. 32%, P = 0.002) through the prevention of cardiac remodeling and the lowering of plasma catecholamine, brain natriuretic peptide, and angiotensin II. These results suggest that the central mechanism plays an important role in the cardioprotective effects of donepezil.

中文翻译：

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脑室内输注多奈哌齐可预防心脏重塑并改善慢性心力衰竭大鼠的预后。


口服多奈哌齐（一种中枢作用的乙酰胆碱酯酶抑制剂）可改善慢性心力衰竭（CHF）大鼠的存活率。然而，多奈哌齐的心脏保护作用机制仍然完全未知。为了阐明潜在的机制，我们检查了多奈哌齐的中央微量输注是否会发挥心脏保护作用。将带有脑室插管的脑室内微量输液泵植入心肌梗塞大鼠体内。将大鼠随机分为中枢盐水治疗组（CST）和中枢多奈哌齐治疗组（CDT）。我们评估了 6 周治疗后的心脏重塑和功能，并检查了 160 天的存活率。与CST相比，CDT通过预防心脏重塑和降低血浆儿茶酚胺、脑钠尿肽和血管紧张素II，显着提高了160天生存率（68% vs. 32%，P = 0.002）。这些结果表明，中枢机制在多奈哌齐的心脏保护作用中发挥着重要作用。