[Comparative effects of carvediol in large, middle, and small dose in preventing left ventricular remodeling after acute myocardial infarction in rats].
OBJECTIVE
To compare the effects of carvedilol in large, middle, or small dose in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats.


METHODS
AMI were conducted by ligating left coronary artery in female SD rats. Twenty-four hours after the procedure, 142 surviving rats were randomly assigned to one of the following groups: AMI control (n = 35), large dose carvedilol (10 mg.kg-1.d-1, n = 37), middle dose carvediol (1 mg.kg-1.d-1, n = 35), and small dose carvediol(0.1 mg.kg-1.d-1, n = 35) Sham-operated rats (n = 16) were selected randomly as non-infarction control. Carvedilol was administered by direct gastric gavage for four weeks. Then hemodynamic studies were performed, and the hearts of the rats were taken out and fixed with 10% formalin and pathologic analysis was performed. Exclusive of the rats with infarct size < 35% or > 55%, complete experimental variables were obtained in 58 rats.


RESULTS
No significant difference was found in MI size (44.5-46.3%, all P > 0.05) among the four AMI groups. Compared with the sham-operated group, a significant increase could be seen in left ventricular end diastolic pressure (LVEDP, 24.5 mm Hg +/- 5.3 mm Hg), left ventricular volume (LVV, 0.92 ml +/- 0.11 ml), left ventricular absolute weight (LVAW, 730 mg +/- 79 mg) and left ventricular relative weight (LVRW) (LVEDP: vs.; LVV: vs.; LVAW: vs. 730 mg +/- 79 mg; P < 0.05-0.001), and a significant decrease could be seen in sphericity index and LV pressure maximal rate of rise and fall (+/- dp/dt) as well as their corrected values (+/- dp/dt/LVSP) among AMI groups (P < 0.01-0.001). In comparison with AMI groups, a dose-dependent and significant decrease could be seen in LVEDP (7.7 mm Hg +/- 1.9 mm Hg, 12.1 mm Hg +/- 2.0 mm Hg, 14.5 mm Hg +/- 4.6 mm Hg), LVV(0.72 ml +/- 0.10 ml, 0.79 ml +/- 0.08 ml, 0.82 ml +/- 0.10 ml), LVAW (589 mg +/- 57 mg, 622 mg +/- 70 mg, 666 mg +/- 57 mg) and LVRW among large, middle, and small dose carvediol groups (all P < 0.01), while a significant increase could be seen in +/- dp/dt and +/- dp/dt/LVSP (all P < 0.05-0.01) among the three carvedilol groups without significant difference among different doses. The sphericity index was significantly increased only in large-dose carvedilol group (1.71 +/- 0.19 vs 1.96 +/- 0.25, P < 0.05).


CONCLUSIONS
Carvedilol in no matter what dose effectively and dose-dependently prevent LV remodeling after AMI and improve hemodynamics and LV function in rats.
Yang
Y
Y
Department of Coronary Heart Disease, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100037, China.
Tang
Y
Y
Zhang
P
P
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage* / Q000494:pharmacology; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D011412:Propanolamines / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol