Frequency dependent effects on Cai transients and cell shortening in myocytes that survive in the infarcted heart

Abstract

Myocytes that survive in the epicardial border zone of the healing canine infarcted heart provide the substrate for inducible reentrant ventricular arrhythmias. These myocytes have been shown to have altered Ca²⁺ currents which could impact on Ca_i homeostasis in these cells. Objective and Methods: To directly measure and compare intracellular Ca²⁺ transients and cell shortening in myocytes dispersed from control noninfarcted hearts with those from epicardial border zone of 5 day infarcted canine hearts using the Ca²⁺ sensitive indicator fura-2/AM. Studies were designed to determine and compare the effects of rate and premature stimulation on intracellular Ca²⁺ in the two cell types. Results: Epicardial cells from noninfarcted hearts (1) exhibited an increase in amplitude of the fura-2 ratio with decreasing pacing cycle length (CL), while cells from the infarcted heart showed the opposite effect; (2) showed more marked acceleration of relaxation of the Ca_i transient with decreasing CL than myocytes from the infarcted heart; (3) exhibited little or no post rest potentiation in contrast to cells from the infarcted heart; and (4) showed a more rapid recovery during restitution protocols than cells from the infarcted heart. Cell shortening differences were also observed between cell populations in that most cells from the infarcted zone did not show any degree of cell shortening despite the reasonable intracellular Ca²⁺ transient. Conclusions: The handling of intracellular Ca²⁺ in myocytes that have survived in the epicardial border zone is very different from that of normal epicardial myocytes suggesting that there may exist marked heterogeneity in intracellular Ca²⁺ handling in cells in the in situ healing infarcted heart. Electrophysiologic implications of these findings are discussed.