Conduction Block in the Human Ischemic Myocardium: Insights from a 1D Electromechanical Model.

Acute myocardial ischemia, caused by a sudden reduction in coronary blood flow, initiates metabolic disturbances that lead to severe pathophysiological consequences. These include electrophysiological alterations, such as changes in action potential morphology and impaired electrotonic coupling between cardiomyocytes, and mechanical dysfunction, characterized by reduced contractile force and subsequent mechanical discoordination across the ventricular wall. This study employs multi-scale mathematical modeling to investigate the effects of acute ischemia on the electromechanical activity of a single human cardiomyocyte and a one-dimensional myocardial tissue. We identify the conditions for conduction block initiation and the parameters governing conduction restoration in ischemic tissue, and analyze the underlying mechanisms. Our simulations demonstrate that conduction slowing in the one-dimensional strand under ischemia directly results from the hyperkalemia-induced reduction in the fast sodium current (iNa). This iNa reduction is enhanced by direct electromechanical coupling and mechano-electric/mechano-calcium feedback in the mechanically and electrically interacting cardiomyocytes of the one-dimensional tissue. Under 15 min ischemia conditions, iNa decreases to a level insufficient to sustain excitation propagation, causing conduction block. Under the conditions of this simulation, where gap junction conductance was held unchanged, the block occurred via the iNa reduction which is itself amplified by mechano-calcium feedback. Furthermore, our model suggests a potential compensatory mechanism against conduction block in ischemic myocardium. Experimental evidence indicates that ischemia can disrupt gap junctions. A moderate reduction in the electrodiffusion coefficient along the strand, simulating reduced gap junction conductance, can convert persistent conduction block into a transient form and even eliminate it completely, facilitating the maintenance of excitation wave propagation.