Short- and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy.
- Author:
Guo-Tian MA
1
;
Xiu-Mei XIE
;
Xiang-Hong WU
;
Xiao-Bin CHEN
;
Ye-Qing FANG
;
Jin HE
Author Information
1. Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Biphenyl Compounds;
therapeutic use;
Cardiomyopathy, Dilated;
chemically induced;
drug therapy;
Creatinine;
blood;
Doxorubicin;
adverse effects;
Drug Therapy, Combination;
Irbesartan;
Male;
Myocardium;
pathology;
Natriuretic Peptide, Brain;
metabolism;
Perindopril;
therapeutic use;
Potassium;
blood;
Rats;
Rats, Sprague-Dawley;
Tetrazoles;
therapeutic use;
Treatment Outcome
- From:
Journal of Central South University(Medical Sciences)
2007;32(4):594-598
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To evaluate the short-term, and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy (DCM).
METHODS:Sprague-Dawley rats were administered adriamycin intraperitoneally to develop DCM. Grouping of rats: Group A contained normal rats, and Group B contained DCM rats. Both Group A and B were not given drug treatment. Group C and D contained DCM rats, however, Group C was administered perindopril 2mg/(kg x d) while Group D was administered perindopril 1mg/(kg x d) and irbesartan 25mg/(kg x d). Brain natriuretic peptide (BNP) was determined by enzyme linked immunosorbent assay; plasma potassium and creatinine were measured; the pathological lesions of cardiac muscle tissues were evaluated after HE staining; and the survival time of each rat during the intervention was recorded.
RESULTS:After the three-week intervention, the plasma concentrations of BNP in Group D were lower than those in Group C (P<0.05). In each group, plasma concentrations of potassium and creatinine showed no significant differences between pre-intervention and post-intervention (P>0.05); pathological lesions of cardiac muscle tissues in both Group C and D were attenuated compared with those in Group B (P<0.01), but pathological lesions of cardiac muscle tissues showed no significant differences between Group C and Group D (P>0.05). Log-rank test showed that the life span of Group C was shorter than that of Group D (P<0.05); Cox regression analysis showed that both combination therapy and monotherapy with perindopril could prolong the survival time, but the effect of combination therapy was more obvious.
CONCLUSION:Combination therapy with perindopril and irbesartan in a rat model of DCM can more effectively improve the cardiac function and long-term prognosis than those monotherapy with perindopril. Both these two treatment plans can attenuate the pathological lesions of cardiac muscle tissues, without elevating the concentrations of plasma potassium and creatinine.
