Electrical and mechanical restitution of the human heart at different rates of stimulation.

Abstract

Action potential duration and contractility are reduced following premature excitations, and gradually increase as the stimulus interval is lengthened. To examine these phenomena of electrical and mechanical restitution in the human heart, we simultaneously measured action potential duration and the maximum rate of left ventricular pressure in five patients undergoing electrophysiological study. Test beats were introduced at varying intervals after the last of a series of steady state intervals. By plotting action potential duration and maximum rate of left ventricular pressure as a function of the test interval, we formed electrical and mechanical restitution curves. When the rate of steady state pacing was increased, there was a decrease in action potential duration and an increase in the maximum rate of left ventricular pressure for all test intervals; i.e., a change in pacing rate affected action potential duration and maximum rate of left ventricular pressure of test responses in a reciprocal fashion. In addition, a higher steady state pacing rate allowed action potentials and contractile responses to be elicited at shorter test intervals, thereby displacing the electrical and mechanical restitution curves to the left. The magnitude of the leftward shift of both curves corresponded closely to the shortening of the steady state action potential duration induced by the increase in pacing rate. These findings confirm for the human heart that both electrical and mechanical restitution occur after membrane repolarization, i.e., as a function of the electrical diastolic interval preceding a beat, and not the stimulus interval.

Mathematical analysis of dynamics of cardiac memory and accommodation: theory and experiment

“…We never saw biphasic APD restitution curves (11,21,24,50) in which the ventricular myocardial restitution curve has a local maximum at short DI. The action potentials at this peak have been referred to as supernormal premature action potentials (3) and are believed to reflect potentiation of the calcium current.…”

Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective

“…Initial conditions and the resulting dynamics may also change over intermediate time scales, such as following periods of sustained pacing, during which memory may accumulate (30, 71,75,79,106,151,206,218). Typically, accumulation of memory flattens APD restitution, an effect that results from augmented rate-dependent activation of the delayed rectifier (75,101,102) and by increased inward rectifier (221).…”

“…Beat-to-beat changes in electrophysiological properties occur over seconds during irregular or rapid cardiac activation and appear to be important determinants of the propensity to develop and sustain arrhythmias, particularly as they relate to the development of dynamical heterogeneity of refractoriness (23, 83,84,186). On a longer time scale of minutes to hours, key electrical properties such as action potential duration (APD) are importantly influenced by an accumulation and dissipation of shortterm cardiac memory, as occurs during prolonged pacing (30,71,79,106). At a still longer time scale of days to months, the heart can remodel, both structurally and functionally, in response to various stressors (3,146,196).…”

A computationally efficient electrophysiological model of human ventricular cells

“…4A). Experimental studies of restitution in human myocardium have also shown biphasic restitution curves (15,28). This phenomenon is still poorly understood and, so far, no ionic models have been developed to reproduce these nonmonotonic curves.…”