Received October 13, 2005
Revised November 9, 2005
Accepted after revision January 30, 2006

¹ University of Parma
² University of Geneva

^* To whom correspondence should be addressed. E-mail: donatella.stilli{at}unipr.it.

	Abstract

We have analysed alterations of alpha-skeletal actin expression and volume fraction of fibrosis in the ventricular myocardium and their functional counterpart in terms of arrhythmogenesis and hemodynamic, in rats with different degrees of compensated cardiac hypertrophy induced by infra-renal abdominal aortic coarctation. The following coarctation calibres were used: 1.3 mm (AC1,3 group), 0.7 mm (AC0,7), and 0.4 mm (AC0,4); age-matched rats were used as controls (C group). One month after surgery, spontaneous and sympathetic-induced ventricular arrhythmias were telemetrically recorded from conscious freely moving animals, while invasive hemodynamic measurements were performed in anaesthetized animals. After sacrifice, subgroups of AC and C rats were used to evaluate in the left ventricle: expression and spatial distribution of alpha-skeletal actin and amount of perivascular and interstitial fibrosis. As compared with C, all AC groups exhibited higher values of systolic pressure, ventricular weight, and ventricular wall thickness. AC0,7 and AC0,4 rats also showed larger amount of fibrosis and up-regulation of alpha-skeletal actin expression associated with a higher vulnerability to ventricular arrhythmias (AC0,7 and AC0,4) and enhanced myocardial contractility (AC0,4). Our results illustrate the progressive changes in the extracellular matrix features accompanying early ventricular remodelling in response to different degrees of pressure overload that may be involved in the development of cardiac electrical instability. We also demonstrate for the first time a linear correlation between alpha-skeletal actin expression increase and degree of compensated cardiac hypertrophy, possibly acting as an early compensatory mechanism to maintain normal mechanical performance.

Key Words: Actin, Cardiac arrhythmia, Hypertension

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