Low dose carvedilol inhibits progression of heart failure in rats with dilated cardiomyopathy.
The cardioprotective properties of carvedilol (a vasodilating beta-adrenoceptor blocking agent) were studied in a rat model of dilated cardiomyopathy induced by autoimmune myocarditis. Twenty-eight days after immunization, surviving Lewis rats (32/43=74%) were divided into three groups to be given 2 mg kg(-1) day(-1) (Group-C2, n=10) or 20 mg kg(-1) day(-1) (Group-C20, n=10) of carvedilol, or vehicle (0.5% methylcellulose, Group-V, n=12). After oral administration for 2 months, body weight, heart weight (HW), heart rate (HR), rat alpha-atrial natriuretic peptide (r-ANP) in blood, central venous pressure (CVP), mean blood pressure (mean BP), peak left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP), +/-dP dt(-1) and area of myocardial fibrosis were measured. Values were compared with those for normal Lewis rats (Group-N, n=10). Two out of 12 (17%) rats in Group-V died from day 28 to day 42 after immunization. No rat died in Groups-C2, -C20 and -N. Although the CVP, mean BP, LVP and +/-dP dt(-1) did not differ among the three groups, the HW, HR and r-ANP in Group-C2 (1.14+/-0.03, 339+/-16 and 135+/-31) and Group-C20 (1.23+/-0.04, 305+/-8 and 156+/-24) were significantly lower than those in Group-V (1.36+/-0.04 g, 389+/-9 beats min(-1) and 375+/-31 pg ml(-1), respectively). The LVEDP in Group-C2 was significantly lower than that in Group-V (7.4+/-1.4 and 12.2+/-1.2 mmHg, respectively, P<0. 05). The area of myocardial fibrosis in Group-C2 was smaller than that in Group-V (12+/-1 and 31+/-2%, P<0.01). These results indicate that a low dose of carvedilol has beneficial effects on dilated cardiomyopathy.
Department of Clinical Pharmacology, Niigata College of Pharmacy, Kamisin-ei-cho, Niigata 950-2081, Japan. watanabe@niigata-pharm.ac.jp
K
K
Watanabe
Y
Y
Ohta
M
M
Nakazawa
H
H
Higuchi
G
G
Hasegawa
M
M
Naito
K
K
Fuse
M
M
Ito
S
S
Hirono
N
N
Tanabe
H
H
Hanawa
K
K
Kato
M
M
Kodama
Y
Y
Aizawa
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002227:Carbazoles / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000077261:Carvedilol; D018450:Disease Progression; D004719:Endomyocardial Fibrosis / Q000503:physiopathology / Q000517:prevention & control; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009205:Myocarditis / Q000150:complications*; D009929:Organ Size / Q000187:drug effects; D011412:Propanolamines / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016277:Ventricular Function, Left
D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol