Markedly different effects on ventricular remodeling result in a decrease in inducibility of ventricular arrhythmias.
OBJECTIVE
The purpose of this study was to determine whether the type and extent of ventricular remodeling after infarction influence inducibility of ventricular arrhythmias after infarction.


BACKGROUND
Although serious ventricular arrhythmias after infarction are related to ventricular dysfunction, the relation between inducibility of ventricular arrhythmias and ventricular remodeling remains incompletely understood.


METHODS
Rats that survived ligation of the left anterior descending coronary artery (n = 218) were randomized to receive placebo (saline solution) or captopril or propranolol therapy and were followed up for 5 weeks. Hemodynamic and neurohumoral blood measurements were obtained, and therapy was stopped. Two days later, susceptibility to ventricular arrhythmias was assessed by programmed electrical stimulation, and hearts were prepared for pathologic studies.


RESULTS
Placebo-treated rats with a large myocardial infarction had ventricular dysfunction, marked neurohumoral activation, ventricular enlargement (endocardial circumference 16 +/- 3 [mean +/- SD] to 20 +/- 4 mm, p < 0.05) and increased cardiac fibrosis (volume density of collagen 2.3 +/- 0.8% to 5.6 +/- 2.4%, p < 0.05). In many rats this resulted in easily inducible ventricular arrhythmias (inducibility quotient 4.9 +/- 2.2). Captopril attenuated the development of ventricular dysfunction, neurohumoral activation, ventricular hypertrophy and dilation (endocardial circumference 18 +/- 3 mm) and cardiac fibrosis (3.1 +/- 0.8%, p < 0.05). These modifications were accompanied by decreased inducibility of ventricular arrhythmias (inducibility quotient 1.1 +/- 2.0, p < 0.05). Propranolol did not prevent ventricular dysfunction, had variable effects on neurohumoral activation and led to increased ventricular dilation (endocardial circumference 25 +/- 4 mm, p < 0.05) and cardiac fibrosis (7.7 +/- 1.2%, p < 0.05). Nevertheless, these morphologic changes led to decreased inducibility of ventricular arrhythmias (inducibility quotient 2.2 +/- 2.5%, p < 0.05).


CONCLUSIONS
This study indicates that the inducibility of ventricular arrhythmias can be reduced as a result of markedly different effects on ventricular remodeling, indicating that the relation between ventricular remodeling, arrhythmias and survival is more complex than previously thought.
Bélichard
P
P
Centre de Recherche de l'Hôpital du Sacré-Coeur de Montréal, Québec, Canada.
Savard
P
P
Cardinal
R
R
Nadeau
R
R
Gosselin
H
H
Paradis
P
P
Rouleau
J L
JL
D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D002304:Cardiac Pacing, Artificial; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000188:drug therapy; D011433:Propranolol / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017180:Tachycardia, Ventricular / Q000209:etiology* / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology
D002216:Captopril; D011433:Propranolol