Intra-Myocardial Slow Force Response in Heterogeneous Myocardium

Abstract

Recently we have reported on an intra-myocardial slow force response (SFR_IM) of myocardium to changes in the mechanical environment (Markhasin ea, PBMB, 2012). In contrast to SFRs referred to changes in cardiac muscle contractility in response to external (to the heart) mechanical stimuli, SFR_IM ensued from internal mechanical interactions of muscle segments in heterogeneous myocardium. We revealed SFR_IM in two interacting myocardial elements, referred to as the muscle duplex, presenting a simplest possible model of heterogeneous myocardium. We found beat-to-beat changes in the overall duplex force developed by end-to-end coupled muscles upon duplex formation. After duplex disconnection, the individual force produced by each muscle differed significantly from the baseline level prior to muscle coupling, thus pointing out to changes in muscle contractility. SFR_IM in muscle duplexes were accompanied with slow and opposite changes in the action potential and Ca2+ transient in the cardiomyocytes of interacting muscle elements. The SFR_IM phenomena were initially identified by means of mathematical modeling, and subsequently confirmed in physiological experiments involving native cardiac muscles. The SFR_IM were specified for isometric contractions of in-series duplexes where cyclic deformations of muscle segments under a constant length of the pair governed intracellular mechano-chemical and mechano-electrical mechanisms of excitation-contracting coupling contributing to the SFR_IM. Here we present effects of the mechanical load on the SFR_IM in isotonic and physiological modes of contraction of in-series muscle duplexes. We showed that muscle interaction during the isometric phase of duplex contraction determine the amplitude and duration of subsequent duplex shortening, depending on the load value. SFR_IM modifies the force-length and force-velocity dependences in interacting muscles depending on the duplex activation sequence. The results suggest the essential role of SFR_IM in the isovolumetric phase of ventricular contraction in the intact heart. Supported by UB RAS (12-M-14-2009, 12-П-4-1067).