Cellular and molecular remodeling in a heart failure model treated with the beta -blocker carteolol

• Published in: American journal of physiology. Heart and circulatory physiology 1999-05, Vol.276 (5), p.H1678-H1690, Article H1678
• Main Authors: Gwathmey, Judith K, Kim, Catherine S, Hajjar, Roger J, Khan, Farid, DiSalvo, Thomas G, Matsumori, Akira, Bristow, Michael R
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1999.276.5.H1678

1  Integrated Physiology Research Laboratories, Boston University School of Medicine, Cambridge, Massachusetts 02138; 2  Whitaker Cardiovascular Institute, Boston, Massachusetts 02118; 3  Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts 02114; 4  Division of Cardiology, University of Colorado, Denver, Colorado 80262; and 5  Third Division, Department of Internal Medicine, Kyoto University, Kyoto 606, Japan Broad-breasted white turkey poults fed furazolidone developed dilated cardiomyopathy (DCM) characterized by ventricular dilatation, decreased ejection fraction, 1 -receptor density, sarcoplasmic reticulum (SR) Ca 2+ -ATPase, myofibrillar ATPase activity, and reduced metabolism markers. We investigated the effects of carteolol, a -adrenergic blocking agent, by administrating two different dosages (0.01   and 10.0 mg/kg) twice a day for 4 wk to control and DCM turkey poults. At completion of the study there was 59% mortality in the nontreated DCM group, 55% mortality in the group treated with the low dose of carteolol, and 22% mortality in the group treated with the high dose of carteolol. Both treated groups showed a significant decrease in left ventricle size and significant restoration of ejection fraction and left ventricular peak systolic pressure. Carteolol treatment increased -adrenergic receptor density, and the high carteolol dose restored SR Ca 2+ -ATPase and myofibrillar ATPase activities, along with creatine kinase, lactate dehydrogenase, aspartate transaminase, and ATP synthase activities, to normal. These results show that -blockade with carteolol improves survival, reverses contractile abnormalities, and induces cellular remodeling in this model of heart failure. -receptor antagonist; turkey; cellular mechanisms