Effect of age and sex on the incidence of ventricular arrhythmia in a rat model of acute ischemia.

ABSTRACT

BACKGROUND: The impact of sex and age on the arrhythmic susceptibility within the setting of acute ischemia is masked by the fact that acute coronary events result from coronary artery disease appearing with age much earlier among men than among women. METHODS AND RESULTS: LAD ligation or sham operations were performed in rats of both sexes at the age 3 and 24 months. An ECG was recorded continuously for 6 h after the operation. The number of early and late premature ventricular beats (PVBs), episodes of ventricular tachycardia (VT) and fibrillation (VF), heart rate, QRS, QT and Tpeak-Tend duration were analysed. Epicardial action potentials were recorded in vivo, Ca2+ signaling was evaluated in isolated cardiomyocytes, fibrosis and connexin-43 expression and localization were measured in the septum. PVBs, VT and VF episodes are much more common in older males than in young males and females independently from their age. Fibrosis with varying intensity in different muscle layers, hypertrophy of cardiomyocytes, reduced number of gap junctions and their appearance on the lateral myocyte membrane, QT prolongation, increase transmural dispersion of repolarisation and a decreased function of SERCA2a may increase the propensity to arrhythmia within the setting of acute ischemia. CONCLUSION: We show that the male sex, especially in case of older individuals is a strong predictor of increased arrhythmic susceptibility within the acute ischemia setting regardless of its impact on the occurrence of cardiovascular diseases. A personalized sex-dependent prevention treatment is needed to reduce the mortality in acute phases of myocardial infarction.