Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin convertingenzyme inhibitor (ACEI) is the cornerstone in its treatment However, CHF continues to progress ...Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin convertingenzyme 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 shamoperated rats (Sham), MIcontrol rats (MIcontrol), MI rats treated with ramipril 3 mg/kg (MIramipril) or TCV116 2 mg/kg (MITCV116) per day, half dosage (MI1/2R&T) or full dosage (MIR&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), Btype natriuretic peptide (BNP), transforming growth factorβ1 (TGFβ1), collagen I and Ⅲ were quantified with reverse transcription polymerase chain reaction (RTPCR) 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 MIcontrol, MIramipril, MITCV116, MI1/2R&T and MIR&T, respectively, no statistical significance for all) Compared with shamoperated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P<001); while their hemodynamic parameters were significantly impaired (P<001), and in terms of spontaneous deaths survival rate shortened (P<005) Compared with MI rats without therapy, MI rats treated with each single drug showed significant attenuation of mRNA expressions of cardiac molecule genes (P<001); while their hemodynamic parameters were significantly improved (P<005 or P<001), and in terms of spontaneous deaths survival rate prolonged (P<005) 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<005 vs monotherapy); while LVEDP was further lowered (P<005 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 treatmentsConclusions 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展开更多
文摘Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin convertingenzyme 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 shamoperated rats (Sham), MIcontrol rats (MIcontrol), MI rats treated with ramipril 3 mg/kg (MIramipril) or TCV116 2 mg/kg (MITCV116) per day, half dosage (MI1/2R&T) or full dosage (MIR&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), Btype natriuretic peptide (BNP), transforming growth factorβ1 (TGFβ1), collagen I and Ⅲ were quantified with reverse transcription polymerase chain reaction (RTPCR) 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 MIcontrol, MIramipril, MITCV116, MI1/2R&T and MIR&T, respectively, no statistical significance for all) Compared with shamoperated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P<001); while their hemodynamic parameters were significantly impaired (P<001), and in terms of spontaneous deaths survival rate shortened (P<005) Compared with MI rats without therapy, MI rats treated with each single drug showed significant attenuation of mRNA expressions of cardiac molecule genes (P<001); while their hemodynamic parameters were significantly improved (P<005 or P<001), and in terms of spontaneous deaths survival rate prolonged (P<005) 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<005 vs monotherapy); while LVEDP was further lowered (P<005 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 treatmentsConclusions 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
