CARDIAC-HYPERTROPHY, ARRHYTHMOGENICITY AND THE NEW MYOCARDIAL PHENOTYPE .2. THE CELLULAR ADAPTATIONAL PROCESS

Ventricular fibrosis is not the only structural determinant of arrhyth mias in left ventricular hypertrophy. In an experimental model of comp ensatory cardiac hypertrophy (CCH) the degree of cardiac hypertrophy i s also independently linked to ventricular arrhythmias. Cardiac hypert rophy reflects the level of adaptation, and matches the adaptational m odifications of the myocardial phenotype. We suggest that these modifi cations have detrimental aspects. The increased action potential (AP) and QT duration and the prolonged calcium transient both favour sponta neous calcium oscillations, and both are potentially arrhythmogenic an d linked to phenotypic changes in membrane proteins. To date, only two ionic currents have been studied in detail: I-to is depressed (likely the main determinant in AP duration), and I-f, the pacemaker current, is induced in the overloaded ventricular myocytes. In rat CCH, the tw o components of the sarcoplasmic reticulum, namely Ca2+-ATPase and rya nodine receptors, are down-regulated in parallel. Nevertheless, while the inward calcium current is unchanged, the functionally linked duo c omposed of the Na+/Ca2+ exchanger and (Na+, K+)-ATPase, is less active . Such an imbalance may explain the prolonged calcium transient. The c hanges in heart rate variability provide information about the state o f the autonomic nervous system and has prognostic value even in CCH. T ransgenic studies have demonstrated that the myocardial adrenergic and muscarinic receptor content is also a determining factor. During CCH, several phenotypic membrane changes participate in the slowing of con traction velocity and are thus adaptational. They also have a detrimen tal counterpart and, together with fibrosis, favour arrhythmias. (C) 1 997 Elsevier Science B.V.