Carvedilol may alleviate late cardiac remodelling following surgical ventricular restoration.
OBJECTIVE
Surgical ventricular restoration (SVR) can be effective to treat ischaemic cardiomyopathy or left ventricular (LV) aneurysm. However, the initial improvement in LV function does not always last long because of LV remodelling. Beta-blockers prevent LV remodelling of failing hearts; however, their effects following SVR have not been elucidated. Thus, we sought to investigate the effects of a potent beta-blocker, carvedilol, on LV remodelling and function following SVR in rats with myocardial infarction.


METHODS
Rats, which developed LV aneurysm 4 weeks after coronary artery ligation, underwent SVR. They were orally administered a vehicle (vehicle group), and low or high dose of carvedilol (20 or 50 mg kg(-1)day(-1) for C20 or C50 group) for 4 weeks following SVR (n=7 in each group).


RESULTS
Four weeks following SVR, late cardiac remodelling was alleviated only in the C50 group (LV end-diastolic area: 65+/-4 mm(2) vs 74+/-11 mm(2) and 76+/-11 mm(2) for C50, C20 and vehicle groups; p=0.039 and p=0.013, respectively). There was no difference in LV systolic function (end-systolic elastance) among the three groups; however, LV diastolic functions (LV end-diastolic pressure and the time constant of isovolumic relaxation) were significantly better in the C20 and C50 groups. Histologically, the percentage of myocardial fibrosis in the C50 group (4.1+/-0.2%) was lower than those in the C20 (6.7+/-0.4%, p<0.0001) and vehicle (7.5+/-0.6%, p<0.0001) groups. The mRNA expression of transforming growth factor-beta1 and brain natriuretic peptide in the C50 group were lower than those in the C20 and the vehicle groups.


CONCLUSIONS
High-dose carvedilol alleviated LV remodelling and diastolic dysfunction following SVR accompanying with reduction in myocardial fibrosis. Blockade of beta-adrenergic receptor may be a promising adjuvant therapy in patients following SVR.
Yoshikawa
Eiji
E
Department of Cardiovascular Surgery, Kyoto University, Graduate School of Medicine, Sakyo, Kyoto, 606-8507, Japan.
Marui
Akira
A
Tsukashita
Masaki
M
Nishina
Takeshi
T
Wang
Jian
J
Muranaka
Hiroyuki
H
Ikeda
Tadashi
T
Komeda
Masashi
M
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D002227:Carbazoles / Q000627:therapeutic use*; D006328:Cardiac Catheterization; D000077261:Carvedilol; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics; D009929:Organ Size; D011182:Postoperative Care / Q000379:methods; D011412:Propanolamines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain