Masson Serge, Staszewsky Lidia, Annoni Giorgio, Carlo Eleonora, Arosio Beatrice, Bai Antonio, Calabresi Carmen, Martinoli Elena, Salio Monica, Fiordaliso Fabio, Scanziani Eugenio, Rudolph Amy E, Latini Roberto
Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Card Fail. 2004 Oct;10(5):433-41. doi: 10.1016/j.cardfail.2004.02.010.
The incidence of cardiovascular diseases increases rapidly with age, and the elderly suffer higher morbidity and mortality. Aldosterone blockers have shown benefits in patients with left ventricular (LV) dysfunction and heart failure after myocardial infarction (MI). However, aldosterone blockade efficacy has not been explored in aged animals with MI. Methods and results Small-to-moderate MI was induced by coronary artery ligation in 16-month old rats, divided into 3 groups: sham-operated (control, n = 9), MI (n = 9), and MI fed a diet containing eplerenone (120 mg/kg/day, MI+Eplerenone, n = 9) given 18 days postsurgery and up to sacrifice 3 months later. At sacrifice, untreated MI rats did not show overt systolic dysfunction but they had (1) echocardiographic evidences of impaired relaxation (increase of E wave deceleration time and of isovolumic relaxation time, decrease of peak E wave velocity), (2) hemodynamically impaired LV relaxation (LV -dP/dt from 7413 +/- 720 to 4956 +/- 475 mm Hg/s, P < .05), and (3) significant increase of collagen content in LV interstitium (from 4.27 +/- 0.23 to 5.34 +/- 0.24%, P < .01) and in aorta (from 19 +/- 1 to 24 +/- 2%, P < .05). Eplerenone normalized echocardiographic and hemodynamic evidences of diastolic dysfunction, as well as myocardial interstitial collagen and aortic fibrosis (all parameters statistically different from untreated MI).
In aged rats with small to moderate MI, eplerenone normalized diastolic relaxation, possibly through a reduction of interstitial fibrosis.
心血管疾病的发病率随年龄增长而迅速上升，老年人的发病率和死亡率更高。醛固酮阻滞剂已显示出对左心室（LV）功能障碍和心肌梗死（MI）后心力衰竭患者有益。然而，醛固酮阻断在老年心肌梗死动物中的疗效尚未得到研究。
通过冠状动脉结扎在16月龄大鼠中诱导轻至中度心肌梗死，分为3组：假手术组（对照组，n = 9）、心肌梗死组（n = 9）和心肌梗死组并给予依普利酮饮食（120 mg/kg/天，心肌梗死+依普利酮组，n = 9），术后18天开始给药，直至3个月后处死。处死时，未治疗的心肌梗死大鼠未表现出明显的收缩功能障碍，但存在（1）舒张功能受损的超声心动图证据（E波减速时间和等容舒张时间增加，E波峰值速度降低），（2）血流动力学上左心室舒张功能受损（左心室 -dP/dt从7413±720降至4956±475 mmHg/s，P <.05），以及（3）左心室间质和主动脉中胶原蛋白含量显著增加（分别从4.27±0.23%增至5.34±0.24%，P <.01；从19±1%增至24±2%，P <.05）。依普利酮使舒张功能障碍的超声心动图和血流动力学证据以及心肌间质胶原蛋白和主动脉纤维化恢复正常（所有参数与未治疗的心肌梗死组在统计学上有差异）。
在轻至中度心肌梗死的老年大鼠中，依普利酮可能通过减少间质纤维化使舒张期松弛恢复正常。
