Carvedilol may alleviate late cardiac remodelling following surgical ventricular restoration

• Published in: European journal of cardio-thoracic surgery 2010-02, Vol.37 (2), p.362-367
• Main Authors: Yoshikawa, Eiji, Marui, Akira, Tsukashita, Masaki, Nishina, Takeshi, Wang, Jian, Muranaka, Hiroyuki, Ikeda, Tadashi, Komeda, Masashi
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Animals; Biological and medical sciences; Carbazoles - therapeutic use; Cardiac Catheterization; Cardiology. Vascular system; Coronary heart disease; Drug Evaluation, Preclinical - methods; Fibrosis; Gene Expression Regulation - drug effects; Heart; Heart failure; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart Ventricles - metabolism; Heart Ventricles - pathology; Heart Ventricles - surgery; Hemodynamics; Ischaemic heart disease; Male; Medical sciences; Myocardial Infarction - physiopathology; Myocardial Infarction - surgery; Myocardium - pathology; Myocytes, Cardiac - pathology; Natriuretic Peptide, Brain - biosynthesis; Natriuretic Peptide, Brain - genetics; Organ Size; Pneumology; Postoperative Care - methods; Propanolamines - therapeutic use; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Surgical ventricular restoration; Transforming Growth Factor beta1 - biosynthesis; Transforming Growth Factor beta1 - genetics; Ventricular Remodeling - drug effects
• ISSN: 1010-7940; 1873-734X
• DOI: 10.1016/j.ejcts.2009.04.072

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 β-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 mm2 vs 74 ± 11 mm2 and 76 ± 11 mm2 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-β1 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 β-adrenergic receptor may be a promising adjuvant therapy in patients following SVR.