Experimental and computational studies of strain–conduction velocity relationships in cardiac tissue

Abstract

Velocity of electrical conduction in cardiac tissue is a function of mechanical strain. Although strain-modulated velocity is a well established finding in experimental cardiology, its underlying mechanisms are not well understood. In this work, we summarized potential factors contributing to strain-velocity relationships and reviewed related experimental and computational studies. We presented results from our experimental studies on rabbit papillary muscle, which supported a biphasic relationship of strain and velocity under uni-axial straining conditions. In the low strain range, the strain-velocity relationship was positive. Conduction velocity peaked with 0.59 m/s at 100% strain corresponding to maximal force development. In the high strain range, the relationship was negative. Conduction was reversibly blocked at 118+/-1.8% strain. Reversible block occurred also in the presence of streptomycin. Furthermore, our studies revealed a moderate hysteresis of conduction velocity, which was reduced by streptomycin. We reconstructed several features of the strain-velocity relationship in a computational study with a myocyte strand. The modeling included strain-modulation of intracellular conductivity and stretch-activated cation non-selective ion channels. The computational study supported our hypotheses, that the positive strain-velocity relationship at low strain is caused by strain-modulation of intracellular conductivity and the negative relationship at high strain results from activity of stretch-activated channels. Conduction block was not reconstructed in our computational studies. We concluded this work by sketching a hypothesis for strain-modulation of conduction and conduction block in papillary muscle. We suggest that this hypothesis can also explain uni-axially measured strain-conduction velocity relationships in other types of cardiac tissue, but apparently necessitates adjustments to reconstruct pressure or volume related changes of velocity in atria and ventricles.

Cardiac contraction induces discordant alternans and localized block

“…Indeed, there exists experimental and numerical evidence showing that this is the case for moderate values of stretch [25,28], although the relation has often been observed to be biphasic [28]. At larger values of stretch the increase in the resting potential inactivates the sodium channels, resulting in slower conduction and even conduction block.…”

Interstitial volume modulates the conduction velocity-gap junction relationship

“…Cellular excitability is also a major determinant of , but has not been demonstrated to change AR (27,36,45). Albumin and mannitol preferentially changed T and thereby AR , suggesting that cellular excitability may not be the principal mechanism involved.…”

“…It is possible that increased V IS causes G j uncoupling due to increased mechanical stress (27). Likewise, decreasing V IS may facilitate G j formation by bringing cells closer together (8).…”

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

“…The Q-T interval of the electrocardiogram, a measure of the delay between ventricular depolarization and repolarization, has been observed to lengthen, and the Twave to flatten, when ventricular contraction occurs rapidly against a reduced afterload, in animal tissue preparations and in the human heart [42,43]. Commonly this affect is attributed to changes in action potential duration that lead to dispersion of the repolarization gradient, though the nature of these changes is unsettled and is likely dependent on heart rate [44][45][46][47][48].…”

“…Experiments in intact and perfused rabbit hearts have shown conduction slowing with ventricular volume loading, a change which would increase apparent ventricular repolarization time [48,49]. Experiments in a variety of tissue preparations have yielded acceleration, deceleration, or biphasic changes in conduction velocity under several modalities of tissue stretch [47,49]. Such electrophysiological changes may contribute to susceptibility to reentrant arrhythmia in tissue regionally affected by disease or dyssynchrony [36,45,46,49,50].…”