Mechano-electrical feedback in ventricular myocardium

In the past, cardiac arrhythmias have been most commonly perceived as a result of eEectricaZ disorders of the heart muscle. As this issue of the journal demonstrates, there is mounting evidence that arrhythmias may also be produced by mechanical perturbations or disorders of the myocardium. Clinical data have long suggested that ventricular arrhythmias occur more frequently in patients who suffer from heart failure, dilated cardiomyopathy, ventricular volume or pressure overload, mitral valve prolapse, or dysynergistic ventricular contraction and relaxation 1 111. A potential common mechanism underlying all of these observations may be that dilatation or stretch of the myocardial tissue may lead to electrophysiologic changes which produce or facilitate arrhythmias. The phenomenon that electrophysiological changes may result from regional mechanical stretch or global hemodynamic over-load has been termed “contraction-excitation coupling” [12 or “mechano-electrical feedback” 113,141. In the past, however, this phenomenon has not been sufficiently appreciated within the mainstream of cardiovascular research. One reason may be the paucity of direct cellular data on mechano-electrical feedback. It is extremely difficult to maintain a fragile glass-microelectrode stably within a cell of a vigorously beating heart and even harder to ascertain the effects of simultaneously imposed mechanical perturbations. The body surface ECG, on the other hand, is too insensitive and nonspecific to characterize the electrophysiologic changes that result from mechanical strain and promote stretch-activated arrhythmias. Monophasic action potential (MAP) recording, which accurately depicts the time course of transmembrane action potentials while being less sensitive to motion artifacts than intracellular recordings 15,161, has been an important tool in evaluating stretch-induced electrophysiological changes in the intact heart. More recently, significant progress has been made toward identifying and characterizing myocardial stretch-activated channels (SACS) by patch clamp technique [17-201. This review summarizes the current state of knowledge on stretch-induced electrophysiological effects and arrhythmias. Some of these concepts have been expressed in a previous publication [21, and newer observations will be presented and discussed in greater detail in the original papers contained in this focus issue of Cardiovascular Research.