Cholinergic stimulation improves electrophysiological rate adaptation during pressure overload-induced heart failure in rats

Figures

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  Fig. 1.. Optical mapping and signal analysis. A: schematic of RH237 fluorescence image acquisition showing excitation and emission wavelengths, the location of the pacing electrode, and LV epicardial region that was mapped. B: illustration of beat analysis for the last five beats of each PCL within the dynamic pacing protocol. After signal measurement for each pixel, per-pixel means were computed from the last four beats. Global means were then computed from per-pixel means. C: APD60 vs. DI dispersion analysis diagrams. Left: scatterplot showing APD60 vs. DI at one PCL and the predicted relationship PCL = APD + DI (blue dotted line). APD60 vs. DI radial distance (black arrow) and radial angle (θ) were measured to quantify the location of each pixel’s APD60 vs. DI point from the global mean APD60 vs. DI restitution point (large filled circle). Middle: scatterplot showing low APD60 vs. DI dispersion (top), with most points falling along the predicted line. Radial distance vs. radial angle plots of low APD60 vs. DI dispersion (bottom) have most points falling within 10° segments centered at 135° (crosses) and 315° (open circles). Right: scatterplot showing high APD60 vs. DI dispersion (top),…

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  Fig. 2.. Heterogeneous APD60 maps. A: per-pixel APD60 mean maps with insets showing the last optical AP of the 250 ms PCL. In the insets, circles mark onset of the AP upstroke (red), AP activation (blue), and 60% of AP repolarization (green). Axes units are pixels, with 118 µm/pixel. B: per-pixel APD60 mean maps at 150 ms PCL. C: histograms of APD60 maps shown in A and B. Global mean and standard deviation are marked with dotted lines in each histogram. APD60, action potential duration at 60% repolarization; AP, action potential; PCL, pacing cycle length.

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  Fig. 3.. APD60 restitution analysis. A: global APD60 mean values for each PCL, with sample size listed below datapoints. B: APD60 restitution plot for captured PCLs using global APD60 (seen in A) and DI mean values. The dotted rectangle denotes the window of data shown in E. C: fitted APD60 restitution curves plotted with restitution points for each PCL. D: APDss computed from each heart’s fitted APD60 restitution curve. P values for group comparisons are listed in Table 1. E: restitution points for 175 ms and 150 ms PCL expanded from the dotted rectangle region shown in B. The definition of restitution vector angle (θ) is shown in the diagram above. F: APD60 restitution vector angles computed from 175 ms PCL to 150 ms PCL (Sham n = 7, TAC n = 5, and TAC + CNO n = 6). P values for group comparisons are listed in Table 1. G: representative APD60 restitution vector angle maps for each group. Axes units are pixels, with 118 µm/pixel. All error bars indicate standard error of the mean (SEM). APD60, action potential duration at 60% repolarization; APDss, APD60 steady state; CNO, clozapine N-oxide; DI, diastolic interval; PCL, pacing cycle length; TAC, transverse-ascending aortic constriction.

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  Fig. 4.. Disrupted conduction continuity. A: AT map with overlaid CV vectors for the last AP of 250 ms and 150 ms PCLs. Axes units are pixels, with 118 µm/pixel. B: CV histograms for the per-pixel means of the last four beats of 250 ms and 150 ms PCLs for the hearts shown in A. Global mean and standard deviation are marked with dotted lines in each histogram. C: conduction loss maps representing the number of values used at each per-pixel APD60 mean for both 250 ms and 150 ms PCLs. Axes units are pixels, with 118 µm/pixel. D: percent change between 250 ms and 150 ms in the number of pixels with four values used for per-pixel APD60 mean. Sham, n = 6; TAC, n = 5; and TAC + CNO, n = 5. E: CV global mean values for each captured PCL. F: CV restitution plot for captured PCLs using global CV (seen in E) and DI mean values. Sample size for E and F same as Fig. 3A. All error bars indicate standard error of the mean (SEM). APD60, action potential duration at 60% repolarization; AP, action potential; AT, activation time; CNO, clozapine-N-oxide; CV, conduction velocity; PCL, pacing cycle length.

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  Fig. 5.. APD60 vs. DI dispersion analysis. A: APD60 vs. DI dispersion two-dimensional histograms for 150 ms PCL using each pixel’s per-pixel APD60 and DI mean value. Concentric dotted circles represent 25 ms radial distance from global mean restitution point. Dotted diagonal line represents the predicted PCL = APD + DI line. Schematic inset refreshes Fig. 1C concepts of radial distance (black arrow) and radial angle (θ). B: radial distance maps at 150 ms PCL. C: radial angle maps for 150 ms PCL. Axes units are pixels, with 118 µm/pixel. D: radial distance vs. radial angle scatter plots for 150 ms PCL with line marked for PCL = APD + DI. APD60, action potential duration at 60% repolarization; DI, diastolic interval; PCL, pacing cycle length.

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  Fig. 6.. Segment analysis for rate responsive tissue. A: per-pixel APD60 mean maps for PCLs 250 ms and 150 ms with markers for pixels that are within the APD60 vs. DI 10° segments centered at 135° (crosses) and 315° (circles) along the predicted PCL = APD + DI line. Red box and corresponding inset for TAC highlights a region of increased APD60 vs. DI dispersion due to loss of pixels in 10° segments at 150 ms PCL. Axes units are pixels, with 118 µm/pixel. B: schematic of segment markers refreshing Fig. 1C. C and D: percent of total pixels lying within these 10° segments of the APD60 vs. DI dispersion for PCLs 250 and 150 ms. P values for group comparisons are listed in Table 1. Sample size for (C) Sham, n = 6; TAC, n = 5; and TAC + CNO, n = 6. Sample size for (D) Sham, n = 7; TAC, n = 5; and TAC + CNO, n = 6. All error bars indicate standard error of the mean (SEM). APD60, action potential duration at 60% repolarization; CNO, clozapine-N-oxide; DI, diastolic interval; PCL, pacing cycle length; TAC, transverse-ascending aortic constriction.