[Short- and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy].
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.


CONCLUSIONS
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.
Ma
Guo-Tian
GT
Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, China.
Xie
Xiu-Mei
XM
Wu
Xiang-Hong
XH
Chen
Xiao-Bin
XB
Fang
Ye-Qing
YQ
He
Jin
J
D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000188:drug therapy*; D003404:Creatinine / Q000097:blood; D004317:Doxorubicin / Q000009:adverse effects; D004359:Drug Therapy, Combination; D000077405:Irbesartan; D008297:Male; D009206:Myocardium / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D020913:Perindopril / Q000627:therapeutic use*; D011188:Potassium / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
D001713:Biphenyl Compounds; D013777:Tetrazoles; D020097:Natriuretic Peptide, Brain; D004317:Doxorubicin; D003404:Creatinine; D000077405:Irbesartan; D011188:Potassium; D020913:Perindopril