Effect of cellular inhomogeneity on cardiac tissue mechanics based on intracellular control mechanisms

Our earlier description of the intracellular control (IC) of contraction of a single cell, based on coupling calcium kinetics with cross-bridge cycling, is extended here to study the performance of a multicellular inhomogeneous tissue common in pathophysiological situations. Inhomogeneity in calcium affinity or in cross-bridge kinetics is first simulated by analyzing two fiber segments connected as parallel or serial duplexes. The calculated characteristics of the parallel duplex are tested against our experimental data with two parallel nonuniform rat papillary fibers. The predicted serial duplex behavior is compared with reported experimental data of the effects of segmental hypoxia along a papillary fiber. Fiber inhomogeneity leads to polyphasic contraction of the fiber segments, reduces muscle length shortening, and affects the control of relaxation. We next investigated the force generated by a nonuniform tissue containing small areas of necrosis, evident in subendocardial infarction. Theoretical analysis suggests that the IC mechanism decreases the extension of cell necrosis by lowering the energy consumption of the viable cells in the ischemic zone. The study emphasizes the importance of IC in determining the global and local function of the inhomogeneous myocardium.