TAO Ze-wei 1HUANG Yuan-wei 2XIA Qiang 3XU Qi-wen1
作者信息
- 1. Department of Cardiology, Chinese People Armed Police Force Hospital of Hunan Province, Changsha 410006, China
- 2. Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
- 3. Department of Physiology, College of Medicine, Zhejiang University, Hangzhou 310006, China
- 折叠
摘要
Abstract
Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin converting-enzyme inhibitor (ACEI) is the cornerstone in its treatment. However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin Ⅱ (Ang Ⅱ) by alternative pathways. The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang Ⅱ type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI). Methods Congestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery. The experiment protocol included sham-operated rats (Sham), MI-control rats (MI-control), MI rats treated with ramipril 3 mg/kg (MI-ramipril) or TCV116 2 mg/kg (MI-TCV116) per day, half dosage (MI-1/2R&T) or full dosage (MI-R&T) combination of the two. At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as β myosin heavy chain (βMHC), B-type natriuretic peptide (BNP), transforming growth factor-β1 (TGF-β1), collagen I and Ⅲ were quantified with reverse transcription polymerase chain reaction (RT-PCR) in the surviving septum myocardium, and survival rates were calculated. Results There were no significant differences in MI sizes (%) among each MI related experimental groups (33±13, 34±14, 33±13, 35±13 and 33±14 for MI-control, MI-ramipril, MI-TCV116, MI-1/2R&T and MI-R&T, respectively, no statistical significance for all). Compared with sham-operated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly impaired (P<0.01), and in terms of spontaneous deaths survival rate shortened (P<0.05). Compared with MI rats without therapy, MI rats treated with each single drug showed significant attenuation of mRNA expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly improved (P<0.05 or P<0.01), and in terms of spontaneous deaths survival rate prolonged (P<0.05). Both half and full dosage combined treatments exerted more powerful effects on improvement of cardiac phenotypic changes and on attenuation of βMHC, BNP mRNA expressions (P<0.05 vs monotherapy); while LVEDP was further lowered (P<0.05 vs monotherapy). However, the total death in MI rats with full dosage combined treatment was more though there were no significant differences when compared with other treatments.Conclusions The results suggest that treatment with appropriate dosage combination of a chronic ACEI and a chronic ARB may further improve cardiac remodeling and cardiac function after MI.关键词
renin-angiotensin-aldosterone system/angiotensin Ⅱ/myocardial infarction/ventricular remodeling/congestive heart failureKey words
renin-angiotensin-aldosterone system/angiotensin Ⅱ/myocardial infarction/ventricular remodeling/congestive heart failure分类
医药卫生
