Global and Regional Voltage and Calcium-Transient Responses to Acute Cardiac Contractility Modulation in Isoproterenol-Treated Rat Hearts with Features Compatible with Early Remodeling

Abstract

Background: Cardiac contractility modulation (CCM) improves cardiac performance in heart failure, but its acute spatial effects on myocardial voltage and calcium-transient behavior remain incompletely characterized, particularly in the setting of early myocardial remodeling. Methods: In this exploratory, fixed-sequence study, isolated Langendorff-perfused hearts from Control and isoproterenol (ISO)-treated rats (n = 5 per group) underwent simultaneous voltage and calcium optical mapping during a 40-s protocol consisting of pre-stimulation (Base), active CCM stimulation (CCM-ON), and post-stimulation (CCM-OFF) phases. Global metrics were derived across the mapped ventricular surface and regional metrics from predefined regions proximal and distal to the stimulation electrodes. No time-matched sham-stimulation condition was included. Results: Relative optical action-potential (AP) and calcium-transient (CaT) amplitudes were approximately 5–6% higher during CCM-ON and CCM-OFF than during Base in both groups. Global AP duration at 90% repolarization (APD90) showed modest phase-dependent prolongation, whereas global CaT duration at 90% recovery (CTD90) showed modest shortening. Global CTD90 was longer overall in ISO-treated hearts, without a group-by-phase interaction. Three-way repeated-measures analyses identified phase-by-region interactions for CTD90 and AP–CaT delay (the interval from the 50% AP upstroke to the 50% CaT upstroke) and a group-by-region interaction for CTD90, with no significant phase-by-group-by-region interactions. CTD90 spatial dispersion and the absolute proximal–distal difference in AP–CaT delay showed phase effects, whereas mapped-surface APD90 dispersion did not change detectably. Conclusions: During the acute CCM sequence, CaT recovery and AP–CaT timing showed spatially nonuniform phase-associated patterns in Control hearts and ISO-treated hearts with features compatible with early remodeling, without a parallel detectable increase in mapped-surface APD90 dispersion. These exploratory, hypothesis-generating findings support a spatial dissociation between calcium-related temporal responses and mapped-surface APD90 dispersion under the present experimental conditions.