Effect of Carvacrol, TRP Channels Modulator, on Cardiac Electrical Activity

Figures

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  Figure 1. Representative traces of electrical activity registered on the Langendorff-perfused rabbit hearts. (a) Pseudo-ECGs under spontaneous rhythm in control conditions (black) and at 10, 30, 100, and 300 μM cumulatively increased concentrations of CAR (light green, green, dark green, and light blue, respectively) for 5 min under each condition, followed by 10 min perfusion without the drug (grey). (b) Superimposition of pseudo-ECG traces; same data as in (a). (c) Traces obtained from a unipolar electrogram of the LV under the same experimental conditions as in (a) but during epicardial stimulation. Note: marked slowing in conduction velocity (CV) and depression in T-wave amplitude at 300 μM CAR. Asterisk means electrogram traces presented in every 30 s (not after 5 min), when perfused with CAR at the 300 μM concentration (light blue, blue, dark blue, and navy, respectively).

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  Figure 2. CAR effects on the APs of the Langendorff-perfused rabbit hearts. (a) Representative traces of APs from microelectrodes obtained with atrial, endocardial, and epicardial pacing under control conditions (i.e., Tyrode solution; black) and at 10, 30, 100, and 300 μM cumulatively increased concentrations of CAR (light green, green, dark green and light blue, respectively). Insert: CAR concentrations as indicated in μM. The broken black arrow indicates the start of the stimulus. Solid arrows denote the rightward shift in the AP activation time. (b) Superimposition of AP upstrokes from the same data as in (a). Note change in AP activation times vs. CAR concentrations as indicated. (c) Traces of dV/dtmax (in V/s) obtained at increased concentrations of CAR. AP upstroke velocity values were obtained from the same AP data as in (a). Note the marked decrease in conduction at 300 μM CAR (light blue).

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  Figure 3. Effects of CAR on the OAPs of the Langendorff-perfused rabbit hearts. (a–c) Data obtained at the LV base, middle, and apex, respectively. Superimposition of OAPs and their upstrokes on an expanded time scale (left) of time-dependent changes in AT (grey) and the duration of OAPD20 (yellow), OAPD50 (red), and OAPD90 (green) (middle) of time-dependent changes of fluorescence in a.u. (F, light blue) and changes in the voltage-sensitive fraction of fluorescence in percent (dF/F, blue) versus time (right). The arrows above the graphs of OAPDs and AT (middle) indicate start of perfusion with corresponding concentration of CAR.

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  Figure 4. CAR effects on cardiac electrical activity of rabbit heart recorded by optical mapping using the fluorescent dye di-4-ANBDQBS. Representative optical maps of activation time (AT), conduction velocity (CV), conduction vector maps (C-vector), and OAPD maps (OAPD20, OAPD50, and OAPD90) obtained under control conditions and at 10, 30, 100, 300, and 1000 μM concentrations of CAR. Endocardial pacing was set at 300 ms. The number near the isochrones shows the activation times in AT maps (in ms). The conduction velocity is shown in CV maps (in m/s). AP duration maps are shown for OAPD20, OAPD50, and OAPD90 (in ms). The interval between isochrones is 2 ms for the AT and 0.2 m/s for the CV. The AT was calculated as the time interval from stimulus to 50% depolarization. OAPD20, OAPD50, and OAPD90 were calculated at 20%, 50%, and 90% of repolarization, respectively, from the AT. Note: 1000 μM CAR was applied after the washout period with Tyrode solution without the drug. The corresponding scale bars are given in the left and at the bottom.

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  Figure 5. CAR effects on cardiac electrical activity in a human LV preparation obtained using the fluorescent dye di-4-ANBDQBS. (a) (left to right) schematic view of experimental setup, LV wedge preparation cannulated via left anterior descending coronary artery (LAD), ECG, superimposed OAPs (upper), and their upstrokes (lower); control (black) and 100 μM CAR (green) treatments. Endocardial pacing was set at a 2000 ms period. Representative optical maps obtained during control (b) and 100 μM CAR treatments (c): (left to right) activation time (AT), conduction velocity (CV), conduction vector (C-vector), and OAPD maps (OAPD20, OAPD50, and OAPD90). The corresponding scale bars are given at the bottom. Other notations are the same as in Figure 4.