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

Figures

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  Figure 1. Representative ventricular histology and baseline electrophysiology. (a) Representative Masson’s trichrome-stained ventricular sections from Control and isoproterenol (ISO)-treated hearts. The ISO-treated example shows mild interstitial collagen staining and qualitative alterations in myocardial architecture. (b) Representative activation maps across the mapped ventricular surface. The ISO-treated example shows later completion of ventricular activation. (c,d) Baseline global action potential duration at 90% repolarization (APD90; (c)) and calcium-transient duration at 90% recovery (CTD90 (d)). (e,f) Total ventricular activation time (e) and action potential (AP) upstroke time (f). Data are presented as mean ± standard error of the mean (SEM), with individual hearts shown (n = 5 per group). Between-group comparisons were performed using two-tailed unpaired Welch’s t tests.

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  Figure 2. Global optical responses during acute cardiac contractility modulation. (a) Representative continuous calcium-transient (CaT) fluorescence recordings from Control and ISO-treated hearts during Base, CCM-ON, and CCM-OFF. (b) Representative superimposed optical action-potential (AP) and CaT waveforms. (c,d) Relative optical AP amplitude (c) and CaT amplitude (d), normalized to the corresponding mean Base value within each heart. For each metric and group, one-sample comparisons with 1.0 were Šídák-adjusted across CCM-ON and CCM-OFF. For each metric, phase-specific between-group comparisons using Welch’s t tests were Šídák-adjusted across CCM-ON and CCM-OFF. (e,f) Global APD90 (e) and CTD90 (f). APD90 and CTD90 were analyzed using two-way repeated-measures ANOVA. For each metric, within-group phase comparisons were Tukey-adjusted within each group, and phase-specific between-group comparisons were Šídák-adjusted across the three phases. Data are presented as mean ± SEM, with individual-heart values connected across phases (n = 5 per group). Only statistically significant comparisons are annotated. For panels c and d, * p < 0.05, ** p < 0.01, and *** p < 0.001 versus 1.0 after…

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  Figure 3. Regional CTD90 and AP–CaT delay. (a) Schematic of CCM electrode locations and predefined proximal and distal regions of interest (ROIs). Red circles indicate stimulation electrodes, green squares proximal ROIs, purple squares distal ROIs, and the dashed red outline the mapped field of view. RA, right atrium; LA, left atrium. (b,c) CTD90 in proximal (b) and distal (c) ROIs. (d,e) AP–CaT delay in proximal (d) and distal (e) ROIs. Regional data were analyzed using three-way repeated-measures ANOVA with group, phase, and region, followed by prespecified region-specific comparisons. Within-group phase comparisons were Tukey-adjusted within each group, and between-group comparisons were Šídák-adjusted across phases. Data are mean ± SEM with individual hearts connected across phases (n = 5 per group). Brackets denote significant within-group phase comparisons; # p < 0.05 for ISO versus Control at the corresponding phase after adjustment. Exact results are reported in Section 3.3.

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  Figure 4. Spatial heterogeneity of CTD90, AP–CaT delay, and APD90. (a) Spatial standard deviation (SD) of pixel-wise CTD90 across the mapped ventricular surface. (b) Absolute difference in AP–CaT delay between proximal and distal ROIs. (c) Spatial SD of pixel-wise APD90. Data were analyzed using two-way repeated-measures ANOVA. Within-group phase comparisons were Tukey-adjusted within each group, and between-group comparisons were Šídák-adjusted across phases. Data are mean ± SEM with individual hearts connected across phases (n = 5 per group). Only statistically significant within-group comparisons are annotated. Exact results are reported in Section 3.4.