Tissue-Level Cardiac Electrophysiology Studied in Murine Myocardium Using a Microelectrode Array: Autonomic and Thermal Modulation

Figures

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  Fig. 1. Representative UEGMs recorded from a ventricular tissue slice using the MEA. a The square wave (red) represents the stimulus at a peripheral electrode. The proximal red dot is the negative deflection on the nearest (reference) electrode to the stimulus. Linear conduction is assumed, and the AT at two distal electrodes on the opposite side of the MEA is marked by the red dots, with the arrow indicating direction of propagation. b Magnified UEGMs from a. AT is measured from the stimulus onset to the steepest part of the negative deflection, marked by a red dot. (1) was recorded at the reference electrode, and (2, 3) from the distal electrodes (Color figure online)

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  Fig. 2. Measurement of activation time. In Channel 1, the UEGM is shown with stimulus artefact and negative deflection. Channel 2 displays the first derivative of Channel 1. AT is measured from the stimulus artefact to the maximum negative derivative (grey shaded area). This time is shown in the red circle (Color figure online)

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  Fig. 3. Stability of measurements with time. There were no differences in ERP between groups at any time point during the protocol (n = 4 atria; n = 8 ventricles). And compared to baseline, there were no differences at any time point for either group. For CV, there was no significant difference between groups at baseline (p = 0.985), nor at any time point (n = 4 atria; n = 5 ventricles). Compared to baseline, atria did not differ at any time. Ventricles were significantly different at 7 min (+3.6 cm/s, *p = 0.028) and 21 min (+3.6 cm/s, *p = 0.028), and highly significantly different at 35 min (+7 cm/s, **p < 0.001). There were significant between-group differences in LAT at baseline (Δ1.4 ms, # p = 0.030), at 7 min (Δ1.89 ms, # p = 0.006) and 35 min (Δ1.36 ms, # p = 0.047) (n = 4 atria; n = 5 ventricles). Compared to baseline, there were no significant differences for either group at any time

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  Fig. 4. Response of EP parameters to temperature. Mean atrial ERP at 37 °C was 31 ms, and mean ventricular ERP was 52 ms (*p = 0.015). Compared to 34 °C, atrial ERP was not significantly different at 37 °C, though it approached significance at 40 °C (p = 0.058). Compared to 34 °C, ventricular ERP was highly significantly different at 37 °C and 40 °C (−17 ms and −28 ms, respectively, ## p < 0.001 for both). At 37 °C, mean atrial CV was 36 cm/s, and mean ventricular CV was 57 cm/s (p = 0.088). Compared to 34 °C, there were no significant differences at 37 or 40 °C for either atria or ventricles. Mean atrial LAT at 37 °C was 0.6 ms, and mean ventricular LAT was 1.6 ms (**p < 0.001). Compared to 34 °C, atrial LAT did not differ significantly at 37 °C, but did differ at 40 °C (# p = 0.022). Ventricular LAT was highly significantly different at 37 °C and at 40 °C (## p < 0.001 for both)

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  Fig. 5. Response of EP parameters to carbachol. Compared to baseline, atria had significantly shorter ERP at 10−7 M (−10 ms, # p = 0.042) and 10−6 M carbachol (−21 ms, ## p < 0.001). For ventricles, ERP was significantly shorter at 3 × 10−8 M (−8 ms, # p = 0.032), but did not differ at any other concentrations. Compared to baseline, ventricular CV was highly significantly faster at 3 × 10−8 M (+11 cm/s, ## p = 0.001) and at 10−6 M (+8.5 cm/s, # p = 0.009). There were no differences for atrial CVs. Compared to baseline, there were no significant changes for either chamber in LAT at any concentration of carbachol

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  Fig. 6. Response of EP parameters to isoprenaline. Compared to baseline, atrial ERP was significantly shorter at 10−7 M (−5 ms, # p = 0.028) and 10−6 M isoprenaline (−8 ms, ## p = 0.001); in contrast, ventricular ERP was highly significantly longer at 10−6 M only (+7 ms, # p = 0.004). There were no significant differences in CV with isoprenaline, compared to baseline, for either chamber. And neither were there any differences for atrial LAT at any concentration. For ventricles, however, there were small but significant reductions compared to baseline at each concentration

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  Fig. 7. Response of EP parameters to mexiletine. Compared to baseline, there were no differences in ERP at 10−5 M mexiletine for either chamber, though there were highly significant differences (## p < 0.001) for both atria and ventricles at 10−4 M (+73 ms and +49 ms, respectively). And there were no differences in CV for either group at 10−5 M compared to baseline, but at 10−4 M atrial CV was significantly lower (-16 cm/s, # p = 0.019), and ventricular CV was highly significantly lower (−32 cm/s, ## p < 0.001). There was no difference at 10−5 M mexiletine compared to baseline, in either atrial or ventricular LAT. But atrial LAT was significantly longer at 10−4 M (+0.9 ms, # p = 0.017) and ventricular LAT was highly significantly longer (+2.0 ms, ## p < 0.001)