Increased susceptibility to atrial tachyarrhythmia in spontaneously hypertensive rat hearts

Abstract

Although hypertension is the most prevalent risk factor for atrial fibrillation, there is currently no information available from animal models of hypertension regarding the development of atrial remodeling or increased susceptibility to atrial tachyarrhythmia. Therefore, we examined the susceptibility to atrial tachyarrhythmia and the development of atrial remodeling in excised perfused hearts from male spontaneously hypertensive rats in comparison with age-matched male Wistar-Kyoto normotensive controls at age 3 and 11 months, corresponding with early hypertension and pre-heart failure stages, respectively. The incidence and duration of left atrial tachyarrhythmia induced by burst pacing was greater in hearts from 11-month-old hypertensive animals than either in age-matched controls or in 3-month-old hypertensive rats, although there was no difference between hypertensive and normotensive hearts at 3 months. Thus, hypertension was associated with the development of an arrhythmic substrate. Atrial effective refractory period and the duration of monophasic action potentials recorded from the left atrium were not altered with either hypertension or age, although there were changes in the whole-cell Ca2+ current density of isolated left atrial myocytes. On the other hand, Masson's trichrome staining of wax-embedded sections of left atrium revealed markedly greater interstitial fibrosis in 11-month-old hypertensive rats compared with controls. These data constitute the first experimental evidence that hypertension is associated with the development of a substrate for atrial tachyarrhythmia involving left atrial fibrosis without changes in the atrial effective refractory period and demonstrate that the spontaneously hypertensive rat represents a suitable model for investigating hypertension-associated atrial remodeling.