Effects of high- and low-dose amiodarone on mortality, left ventricular remodeling, and hemodynamics in rats with experimental myocardial infarction.
We examined the effect of high- (AHD) and low-dose (ALD) amiodarone on survival, hemodynamics, and left ventricular remodeling in rats with experimental myocardial infarction (MI). Thirty minutes after coronary artery ligation or sham operation, amiodarone (100 or 20 mg/kg/d) or placebo was given by gavages daily for 8 weeks. Eight weeks later, hemodynamic measurements were performed and left ventricular (LV) volume was determined after KCl-induced cardiac arrest. Early after MI, mortality was lower after both doses of amiodarone. However, excess mortality beginning 15 days after MI outweighed reduced early mortality in rats treated with AHD. Body weight and heart rate were reduced significantly and maximal stroke volume index improved by AHD. In rats with MI, AHD significantly shifted LV pressure-volume curves to the right and increased LV operating volume (2.84 +/- 0.10 versus 2.20 +/- 0.07 mL/kg, P < 0.05). In conclusion, high-dose amiodarone aggravated LV remodeling in rats with large experimental chronic MI probably by lowering heart rate. An early beneficial effect on mortality was probably also lost later by this mechanism. Low-dose amiodarone improved survival without effect on LV remodeling.
Hu
Kai
K
Medizinische Universitätsklinik, Würzburg, Germany.
Gaudron
Peter
P
Ertl
Georg
G
D000638:Amiodarone / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone