PubMed2001
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). CONCLUSION: Carvedilol in no matter what dose effectively and dose-dependently prevent LV remodeling after AMI and improve hemodynamics and LV function in rats.
Adrenergic beta-Antagonists↗