EFFECT OF CELLULAR INHOMOGENEITY ON CARDIAC TISSUE MECHANICS BASED ONINTRACELLULAR CONTROL MECHANISMS

Our earlier description of the intracellular control (TC) of contracti on of a single cell, based on coupling calcium kinetics with cross-bri dge cycling, is extended here to study the performance of a multicellu lar inhomogeneous tissue common in pathophysiological situations. Inho mogeneity in calcium affinity or in cross-bridge kinetics is first sim ulated by analyzing two fiber segments connected as parallel or serial duplexes. The calculated characteristics of the parallel duplex are t ested against our experimental data with two parallel nonuniform rat p apillary 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 su bendocardial infarction. Theoretical analysis suggests that the IC mec hanism decreases the extension of cell necrosis by lowering the energy consumption of the viable cells in the ischemic zone. The study empha sizes the importance of IC in determining the global and local functio n of the inhomogeneous myocardium.