Fig 1.
Schematic illustration of simulation setup.
(A) the extracted virtual ventricular wedge and the pECG setup, (B) the orientation in longitudinal (fiber direction of the sheet), transverse (parallel to fibers of the sheet) and transmural direction (from endocardium to epicardium) and (C) helical transmural fiber orientation.
Table 1.
Heterogeneous conduction velocities (CVs) for different ventricular cell layers and directions and the corresponding calculated diffusion coefficients at 37°C estimated for 3D simulations of a ventricular cell block.
Table 2.
Calculated Q10 temperature coefficients for APD, Vmax time, AP notch and CV for epicardial, M and endocardial cells respectively.
Fig 2.
Visualization of excitation propagation of the simulated myocardial block for selected timestamps and temperatures.
The colors illustrate the cellular membrane potential, where dark blue represents repolarized cells and red the maximum depolarized cells (phase 1 of the AP). The dimension of the simulated myocardial block is 2x2x1cm where the thickness of the epicardial, midmyocardial and endocardial layers are 1mm, 3mm and 6mm, respectively. The stimulus was set in the middle of the left edge of the endocardium. The pictures include the visualized propagation of the outermost endocardial and epicardial layer respectively, the midmyocardial layer with the longest APDs (upper view each) and the transmural excitation in the middle of the block (bottom view each). At time point t = 40ms the hypothermal-induced slowed excitation propagation in all directions is evident. At t = 150ms the myocardial cells are in the plateau phase under normal and hypothermal conditions. A cooling- induced APD prolongation can be observed for the timestamps t = 350ms, t = 420ms and t = 580s where the epicardial layer reveals the shortest repolarization time followed by the endocardial and midmyocardial layer.
Fig 3.
Correlation of the voltage gradients between the myocardial layers and the T wave morphology.
Top: Transmembrane action potentials (AP) representing the outermost epicardial and endocardial layers and the midmyocardial layer with the longest APD for different temperatures of 37°C, 33°C and 27°C. Bottom: calculated pECG across the simulated block. Additionally, a coincident time behavior of the epicardial notch and electrocardiographic J wave as well as repolarization of distinct cell layers and T wave are clearly evident.
Fig 4.
Effects of temperature on APD, QT interval, DOR and TpTe.
(A-B) Temperature dependent prolongation of the APD90 compared to the calculated Q10 curves (Q10 = 0.61) of the epicardial, the midmyocardial and the endocardial layer. A hypothermia-induced prolongation of APD using the model is evident, however, this prolongation is more prominent for temperature dependent CL (Q10-CL) than for fixed CL. (C) Prolongation of the QT interval induced by falling temperatures (calculated based on the simulated pECG for fixed CL and temperature dependent Q10-CL, respectively). (D) Visualization of the transmural averaging effect of APD between coupled cells in the simulated ventricular wedge. All APDs were selected from the center of the epicardial surface to the center of the endocardial surface along the same z-axis until a steady state was reached. The transmural heterogeneity was modeled by a sub-layer of epicardial cells (10% of the total thickness of the ventricular wall, between 0 to 1mm), midmyocardial cells (30%, between 1 to 4mm) and endocardial cells (60%, between 4 to 10mm). (E-F) Indices for transmural dispersion calculated from simulated APD values (DOR) and pECG data (TpTe), showing a linear correlation with decreasing temperature levels. As expected from the simulated results for transmural heterogeneous APD, the variations of APD are higher for temperature dependent Q10-CL than for fixed CL.
Fig 5.
Effects of temperature on epicardial AP notch and J-wave.
(A) Correlation between J wave amplitude and temperature. (B) Correlation between J wave amplitude and amplitude of the epicardial notch when decreasing the temperature from 37° down to 27°C. The dotted lines indicate the linear regression curves (r = -0.99 (A), r = 0.99 (B)). In both experiments the J wave amplitudes were determined based on the simulated transmural pECG for both the fixed CL and temperature dependent Q10-CL. Notch magnitude as percentage of phase 0 amplitude (phase 1 magnitude/phase 0 amplitude ×100) (C), notch duration (D) and notch index (E) increase significantly during cooling.
Fig 6.
Effects of temperature on QRS interval and Vmax.
(A) Correlation between QRS duration and temperature. A cooling-induced prolongation of the QRS interval is evident. The dotted line represents the linear regression curve (r = -0.99, p<0.01). (B) Transmural distribution of Vmax for different temperatures (37°C, 31°C, 27°C). The cooling-induced decrease of Vmax for all cellular regions is obvious. Additionally, the heterogeneity of Vmax based on divergent cell types is shown where the M region yields the highest Vmax value followed by the endocardium and the epicardium.
Fig 7.
Impact of conduction slowing to the QT interval during hypothermia.
The difference between considering and neglecting the cooling-induced decrease in conduction related to the hypothermia-induced QT interval prolongation is displayed. The underlying QT intervals were determined based on the simulated transmural pECG (fixed CL and temperature dependent Q10-CL).