Effect of acute volume load on refractoriness and arrhythmia development in isolated, chronically infarcted canine hearts.

Abstract

In normal isolated, perfused canine ventricles, increased ventricular volume leads to shortening of refractoriness. To test the hypothesis that myocardium within an infarction zone is more susceptible to volume-induced changes in refractoriness than is normal myocardium, we measured strength-interval curves at low and high end-diastolic volumes at control and infarcted sites in 14 isolated, blood perfused, canine hearts with chronic (> 25 days) infarctions. In addition, the effect of volume load on inducing ventricular arrhythmias was studied at one to six sites in 11 hearts. Differences in refractoriness and inducibility at low (22±5 ml) and high (48±6 ml) with elevated wall stress, increased volume load, and regional wall motion abnormalities.4,5 The mechanism of this association between these mechanical factors and arrhythmias has not been determined. Contraction-excitation feedback, the phenomenon whereby changes in the mechanics of myocardial contraction precede and result in changes in membrane potential, may contribute to arrhythmias. Alterations in the action potential duration, diastolic potential, conduction velocity, and automaticity have all been described under different loading conditions in myocardial tissue.6-11 These studies, however, were performed primarily in normal isolated tissues or under non-steady state conditions in intact normal hearts. The purpose of our study was to investigate this phenomenon in chronically infarcted canine ventricles, a model that may simulate the abnormal, scarred hearts in which malignant arrhythmias and congestive heart failure by guest on May 11, 2018 http://circ.ahajournals.org/ Downloaded from

Structural Heterogeneity in the Ventricular Wall Plays a Significant Role in the Initiation of Stretch-Induced Arrhythmias in Perfused Rabbit Right Ventricular Tissues and Whole Heart Preparations

“…Moreover, Josephson 41 revealed that arrhythmias are often initiated from these borders. Calkins et al 8 observed that ventricular dilation shortens the refractoriness of the surviving myocardium in the infarct area rather than the healthy myocardium. Taken together, the following scenario is conceivable.…”

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).…”

Mechanoelectrical Feedback

“…The electrophysiological effects of augmented load have been primarily studied under 2 disparate conditions, ie, during transient stretch (typically Յ50 ms) 1 or steady-state increases in stretch (volume). 2,3 The mechanism underlying the electrophysiological phenomena associated with transient stretch is thought to be related to cardiac mechanosensitive or stretch-activated channels. 4,5 Activation of these channels during diastole results in an inward or depolarizing current, either prolonging action potential duration (APD) or giving rise to an afterdepolarization.…”

“…Increments in ventricular load that occur gradually and are sustained over time are associated with an increase in electrical excitability and shortening of refractoriness due to a parallel decrease in APD. 2,3,6 The cellular mechanism responsible for this form of mechanoelectrical coupling is generally unknown but has also been attributed to stretch-activated channels. 7,8 We hypothesized that an alternative mechanism was responsible for this phenomenon and was related to load-mediated activation of the ␤-adrenergic receptor (␤-AR), which in turn activates a catecholamine-sensitive K ϩ repolarization current.…”