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Effects of Carvedilol on Cardiac Function and Cardiac Adrenergic Neuronal Damage in Rats with Dilated Cardiomyopathy

¹ Department of Clinical Pharmacology, Niigata College of Pharmacy, Niigata, Japan
² Radioisotope Center, Niigata University School of Medicine, Niigata, Japan
³ Department of Medical Technology, School of Health Sciences, Niigata University School of Medicine, Niigata, Japan
⁴ First Department of Medicine, Niigata University School of Medicine, Niigata, Japan
⁵ Daiichi Radioisotope Laboratories, Ltd., Chiba, Japan

Metaiodobenzylguanidine (MIBG) is a reliable marker for the detection of cardiac adrenergic neuronal damage in heart failure. The cardioprotective properties of carvedilol, a vasodilating ß-adrenoceptor–blocking agent, were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Methods: Twenty-eight days after immunization, surviving rats (41/55, or 75%) were divided into 2 groups treated with carvedilol, 2 mg/kg/d (group C, n = 19), or vehicle alone (0.5% methylcellulose, group V, n = 22). After oral administration for 2 mo, heart weight, heart rate, left ventricular end-diastolic pressure (LVEDP), and myocardial fibrosis were measured and compared with those in untreated rats (group N, n = 19). Myocardial uptake of ¹²⁵I-MIBG (differential absorption ratio) in the left ventricle was measured by autoradiography at 10, 30, or 240 min after tracer injection. Results: Four (18%) of 22 rats in group V died between days 28 and 84 after immunization. None of the rats in group C or N died. Heart weight, heart rate, LVEDP, and area of myocardial fibrosis in group C (1.14 ± 0.04 g, 345 ± 16 beats per minute, 7.6 ± 1.5 mm Hg, and 12% ± 1%) were significantly lower than those in group V (1.34 ± 0.04 g, 389 ± 10 beats per minute, 12.3 ± 1.3 mm Hg, and 31% ± 2%). Although the differential absorption ratio was lower at all time points in group V than in group N, uptake after treatment increased in group C, compared with group V, at 10 min (12.5 ± 1.0 vs. 7.6 ± 0.8, not significant), 30 min (10.1 ± 1.1 vs. 6.3 ± 0.9, not significant), and 240 min (6.5 ± 0.5 vs. 2.5 ± 0.2, P < 0.05). The late washout ratio from myocardial radioactivity between 30 and 240 min in group C was lower than that in group V (36% vs. 60%). Conclusion: These observations indicated that carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.

Key Words: ¹²⁵I-MIBG • carvedilol • ß-blocker • dilated cardiomyopathy • heart failure

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