Mechanoelectrical feedback: independent role of preload and contractility in modulation of canine ventricular excitability.

Abstract

Mechanoelectrical feedback, defined as changes in mechanical state that precede and alter transmembrane potential, may have potential importance in understanding the role of altered load and contractility in the initiation and modulation of ventricular arrhythmias. To assess the independent effects of preload and contractility on myocardial excitability and action potential duration, we determined the stimulus strength-interval relationship and recorded monophasic action potentials in isolated canine left ventricles contracting isovolumically. The strength-interval relationship was characterized by three parameters: threshold excitability, relative refractory period, and absolute refractory period. The effects of a threefold increase in left ventricular volume or twofold increase in contractility on these parameters were independently assessed. An increase in preload did not change threshold excitability in 11 ventricles but significantly shortened the absolute refractory period from 205±15 to 191±14 ms (P < 0.001) (mean±SD). Similarly, the relative refractory period decreased from 220±18 to 208±19 ms (P < 0.002). Comparable results were observed when contractility was increased as a result of dobutamine infusion in 10 ventricles. That is, threshold excitability was unchanged but the absolute refractory period decreased from 206±14 to 181±9 ms (P < 0.003), and the relative refractory period decreased from 225±17 to 205±18 ms (P < 0.003). Similar results were obtained when contractility was increased with CaC12, indicating that contractility associated changes were independent of fl-adrenergic receptor stimulation.An increase in preload or contractility was associated with shortening of the action potential. A threefold increase in preload and twofold increase in contractility were associated with a decrease in action potential duration of 22 and 24 ms, respectively. There was a significant linear correlation between action potential duration and excitability (absolute refractory period). The similar effects of increased preload and contractility on threshold excitability and refractoriness can be explained by the action these perturbations have on the time course of repolarization. There-

Stretch-induced arrhythmias in the isolated canine ventricle. Evidence for the importance of mechanoelectrical feedback.

“…Previous studies demonstrate that this measurement of refractoriness is linearly related to the monophasic action potential duration at 90% repolarization, as measured by a contact electrode catheter. 29 At the completion of each study, the left ventricle was carefully trimmed, blotted dry, and weighed. The mean weight was 146±+-22 g (range, 119-180 g).…”

The effects of ventricular end‐diastolic and systolic pressures on action potential and duration in anaesthetized dogs.

“…However, in all these studies the interventions employed were always unphysiological. These include distension of balloons in the cavity of the ventricle (Lerman, Burkhoff, Yue & Sagawa, 1985;Reiter, Synhorst & Mann, 1988), constriction of the aorta (Benditt, Kriett, Tobler, Gornick, Detloff & Anderson, 1985;Dean & Lab, 1989b) and direct stretching of the ventricular wall (Gornick, Tobler, Pritzker, Tuna, Almquist & Benditt, 1986;Gornick, Tobler, Tuna & Benditt, 1989). None of these approaches allows distinction to be made between possible effects of changes in preload and those of changes in afterload, and they do not provide quantitative information on contraction-excitation feedback in the physiologically ejecting heart.…”

Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts

“…cardiac electrophysiology; mechanical stretch; Fourier analysis STRETCH induces the modulation of electrical and mechanical activity in myocytes. The modulation of electrical activity, also referred to as mechanoelectrical feedback (14,35), includes the depolarization of the resting potential (2,17,21,27,28,31,70), alterations of the shape and duration of action potentials (3,11,21,27,28,31,47,57,70), changes in refractoriness (4,7,9,11,27,36,47,48), and the induction of afterdepolarizations (16,18,34). These electrophysiological changes have been related to the generation of different types of cardiac arrhythmias (7, 9, 13-15, 24, 26, 35, 40, 47).…”