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
Copyright© The Japanese Pharmacological Society 1997
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