Long-term effects of beta-adrenergic blocking agent treatment on hemodynamic function and left ventricular remodeling in rats with experimental myocardial infarction: importance of timing of treatment and infarct size.
OBJECTIVE
This study was designed to assess the long-term effects of a beta1-selective beta-adrenergic blocking agent on mortality, in vivo hemodynamic function, left ventricular volume and wall stress in post-myocardial infarction (MI) rats.


BACKGROUND
Beta-blockers have shown beneficial results in clinical studies after MI. However, the underlying mechanism is not yet understood, and experimental studies have shown conflicting results.


METHODS
Bisoprolol (60 mg/kg body weight per day) was given 30 min or 14 days after MI or sham operation.


RESULTS
The mortality rate was reduced only in early bisoprolol-treated rats (29% vs. 46% in untreated rats, p < 0.05). Heart rate was equally reduced in all treatment groups, and the maximal rate of rise of left ventricular systolic pressure (dP/dt(max)) decreased in sham rats and in rats with a small to moderate infarct size. Stroke volume index was unchanged in sham rats and in rats with a small to moderate infarct with early or late bisoprolol treatment and increased in rats with a large infarct in the late bisoprolol group. Left ventricular volume was increased by bisoprolol in sham rats and rats with a small infarct but not in rats with a large infarct.


CONCLUSIONS
Treatments starting early (30 min) or late (14 days) after coronary artery ligation with bisoprolol increased left ventricular volume in sham rats and in rats with a small infarct but not in rats with a large infarct. Late bisoprolol treatment improved stroke volume index, and early bisoprolol treatment reduced diastolic wall stress, in rats with a large myocardial infarct. Thus, bisoprolol effects on remodeling and cardiac performance after myocardial infarction strongly depend on infarct size and timing of treatment. This finding may explain previous controversial results that did not consider infarct size and timing of treatment.
Hu
K
K
Medizinische Klinik II, Klinikum Mannheim der Universität Heidelberg, Germany.
Gaudron
P
P
Ertl
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017298:Bisoprolol / Q000494:pharmacology*; D001835:Body Weight; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D016019:Survival Analysis
D000319:Adrenergic beta-Antagonists; D017298:Bisoprolol