Thoracic dorsal root ganglion stimulation reduces acute myocardial ischemia induced ventricular arrhythmias

FIGURE 1. Experimental design. (A) Timeline of experimental protocol; Twenty-three Yorkshire pigs were randomized to two groups with or without dorsal root ganglion stimulation (DRGS). Single DRGstim catheter was placed at the left T2 DRG and the DRG was stimulated at 1 kHz of frequency. Acute myocardial ischemia was induced by ligating left anterior descending artery (LAD) for 1 h, followed by 2 h of reperfusion. DRGS was initiated 30-min before ischemia and continued throughout the experiment. Photographs of DRGS lead electrodes and representative placement of DRGS lead. DRGS lead was placed along with the spinal dorsal root. CONTROL: LAD ischemia (n = 13). DRGS: LAD ischemia + dorsal root ganglion stimulation (n = 10). (B) 56-electrodes heart mapping and representative cardiac electrogram; Polar map of 56-electrode heart mapping placed around the heart for measuring ventricular electrograms on the left and representative image on the right. (C) Representative cardio electrogram; ARI was measured as the difference between repolarization time (RT) and activation time (AT).

FIGURE 2. Change in electrophysiological parameters at 30 minutes of ischemia - (A) Numbers of ST elevation leads were comparable between the groups (p = 0.367). (B) Representative polar global activation recovery interval maps comparing before and after myocardial ischemia between the groups. (C) At 30 min after ischemia onset, change in activation recovery interval (ARI) was reduced by DRGS. DRGS attenuated cardiac sympathetic excitation in global heart (*p = 0.050). (D) Especially, in the ischemic region it was reduced by DRGS (*p = 0.020). (E) Change in ARI in the remote region of the heart from the ischemia was not reduced by DRGS (p = 0.741). (F) Change in global DOR was reduced by DRGS (*p = 0.016). DOR: dispersion of ARI. LAD: LAD ischemia (n = 11). DRGS: LAD ischemia + dorsal root ganglion stimulation (n = 9). Data are presented as mean ± SEM.

FIGURE 3. Tp-Te interval and Ventricular Arrhythmia assessment. (A) Methods of evaluating Tp-Te interval in the surface ECG based on the tangent method (Left). (B) DRGS reduced change in Tp-Te interval with significant difference (*p = 0.0407). (C) Representative tracings showing ventricular tachycardia (VT) and ventricular fibrillation (VF). (D) DRGS reduced ventricular arrhythmia score which demonstrates that DRGS had physiological effect on reducing cardiac arrhythmias during ischemia (*p = 0.038). (E) Episodes of ventricular fibrillation (VF) were reduced by DRGS during ischemia (*p = 0.024). CONTROL: LAD ischemia (n = 13). DRGS: LAD ischemia + dorsal root ganglion stimulation (n = 10). Data are presented as mean ± SEM.

FIGURE 4. Double labeling of cFos with NeuN expressions in the T2 spinal cord. (A) DRGS decreased double positive cells with cFos and NeuN induced by myocardial ischemia (*p = 0.0476). (B) The representative images from both CONTROL and DRGS groups illustrate NeuN double-labeled cells with cFos. Small arrows indicate single-antibody marked cells, whereas big arrows indicate NeuN co-labeled with CC3 in the “merged” panels. CONTROL: LAD ischemia (n = 4). DRGS: LAD ischemia + dorsal root ganglion stimulation (n = 4). Data are presented as mean ± SEM. Image magnification, 20x and Scale bar, 50 μm.

FIGURE 5. CC3 expressions in the left T2 DRG. (A) CC3 positive cells were significantly reduced with DRGS (A, *p = 0.0084). (B) The representative images from both CONTROL and DRGS groups illustrate NeuN double-labeled cells with CC3. Small arrows indicate single-antibody marked cells, whereas big arrows indicate NeuN co-labeled with CC3 in the “merged” panels. CONTROL: LAD ischemia (n = 5). DRGS: LAD ischemia + dorsal root ganglion stimulation (n = 5). Data are presented as mean ± SEM. Image magnification, 20× and Scale bar, 50 μm.