Effects of carvedilol on cardiac function and cardiac adrenergic neuronal damage in rats with dilated cardiomyopathy.
Metaiodobenzylguanidine (MIBG) is a reliable marker for the detection of cardiac adrenergic neuronal damage in heart failure. The cardioprotective properties of carvedilol, a vasodilating beta-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 (125)I-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%).


CONCLUSIONS
These observations indicated that carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.
Watanabe
Kenichi
K
Department of Clinical Pharmacology, Niigata College of Pharmacy, Kamisinei-cho, Niigata 950-2081, Japan. wastanabe@niigata-pharm.ac.jp
Takahashi
Toshihiro
T
Nakazawa
Mikio
M
Wahed
Mir I I
MI
Fuse
Koichi
K
Tanabe
Naohito
N
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
Ashino
Hiroki
H
Tazawa
Shusaku
S
D019797:3-Iodobenzylguanidine; D000320:Adrenergic Fibers / Q000000981:diagnostic imaging / Q000187:drug effects*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications; D001345:Autoradiography; D002227:Carbazoles / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D000077261:Carvedilol; D005355:Fibrosis; D006321:Heart / Q000294:innervation* / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D009205:Myocarditis / Q000150:complications; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D011412:Propanolamines / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D011917:Rats, Inbred Lew; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D019275:Radiopharmaceuticals; D014665:Vasodilator Agents; D000077261:Carvedilol; D019797:3-Iodobenzylguanidine