Jpn. J. Pharmacol. 74 (2), 171-178 (1997)

Chronic Therapy with Nipradilol, a beta-Adrenergic Blocker, Attenuated Left Ventricular Remodeling Following Myocardial Infarction in Rats

Hiroyuki Sonoki (1), Masaki Nakamura (1) and Akira Takeshita (2)

(1) Tokyo Research Laboratories, Kowa Co., Ltd., 2-17-43 Noguchi-cho, Higashimurayama, Tokyo 189, Japan
(2) Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan

Abstract: We determined whether chronic treatment with nipradilol, a beta-blocker with vasodilating action, reduces left ventricular cavity dilation (LV remodeling) following myocardial infarction and improves cardiac performance. Myocardial infarction was produced by coronary artery ligation in 16-week-old female rats and then the rats were treated for 3-4 months with nipradilol (10 mg/kg/day) or vehicle (0.5% carboxymethylcellulose). The effect of nipradilol on LV remodeling was evaluated by assessing the left ventricular end-diastolic volume index (LVEDVI) and passive pressure-volume relation curve. Since LVEDVI depends on the infarct size, LVEDVI was compared between the vehicle- and nipradilol-treated rats with similar infarct size (10 - 40%). At 3 - 4 months after myocardial infarct production, the left ventricular end-diastolic volume index in the vehicle-treated rats with myocardial infarction was significantly increased, compared with that in the sham-operated rats without infarction. The nipradilol-treated rats had a significantly smaller left ventricular volume index than the vehicle-treated rats (2.04+/-0.16 ml/kg in the vehicle-treated group vs 1.36+/-0.10 ml/kg in the nipradilol-treated group, P < 0.01). The maximum cardiac index achieved by volume loading as an index of cardiac performance was significantly greater in the nipradilol group than the vehicle group (254.5+/-12.6 ml/min kg in the vehicle group vs 347.9+/-20.2 ml/min kg in the nipradilol group, P < 0.01). These results suggest that chronic treatment of nipradilol attenuated left ventricular cavity dilation after myocardial infarction and improved cardiac performance.

Keywords: Remodeling, Myocardial infarction, Cardiac function, Nipradilol, Left ventricular diastolic volume

Copyrightę The Japanese Pharmacological Society 1997

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