Sympathetic modulation of the relation between ventricular repolarization and cycle length.

Abstract

Sympathetic influences on ventricular repolarization are not yet fully elucidated, despite their relevance to arrhythmogenesis. The sympathetic control of repolarization, measured from an endocardial monophasic action potential duration (APD) and from the QT interval, was investigated in 24 anesthetized cats. The effects of right and left stellectomy and of subsequent bilateral stellectomy or beta-blockade on the relation between APD (or QT) and cycle length (CL) at steady state, and on the kinetics of adaptation of APD to a sudden change in cycle length were studied separately. Steady-state APD/CL (or QT/CL) relations were obtained by atrial pacing at different cycle lengths. The kinetics of APD adaptation were evaluated for a sudden decrease of approximately 100 msec in pacing cycle length. The steady-state APD/CL (QT/CL) relation was fitted by the hyperbolic function APD = CL/[(a. CL) + b]. From this, two parameters were computed: 1) 1/a, that is, APD (QT) extrapolated at infinite cycle length (APDmax or QTmax) and 2) the cycle length at which 50% of the total change in APD (or QT) occurred (CL50 = b/a). Right stellectomy reduced APDmax and CL50, an effect reversed by subsequent left stellectomy or beta-blockade (propranolol, 0.5 mg/kg). Left stellectomy prolonged APDmax and CL50. Bilateral stellectomy, in both groups, caused a further increase in these variables. Results were similar for the QT/CL relation. The adaptation kinetics of APD to cycle length was described by the sum of two exponentials. The first time constant (tau fast, about three beats) was unchanged by any intervention; the second (tau slow) was shortened by right stellectomy and prolonged by left stellectomy. The further removal of the remaining stellate ganglion had the same effect in both groups, that is, an increase in tau slow. Thus, sympathetic innervation modulates both the steady-state dependence on cycle length and the kinetics of adaptation to sudden rate changes of ventricular repolarization. The effects of sympathetic influence are asymmetrical. Right stellectomy shortens APDmax and QTmax, reduces CL50, and accelerates APD adaptation to a new steady state. Because these effects are reversed by beta-blockade or left stellectomy, they are likely to be due to a reflexly enhanced sympathetic outflow to the ventricles through the left-sided nerves.