Abstract 15532: Chronic Autonomic Regulation Therapy Mitigates Adverse Cardiac Remodeling Induced by Myocardial Infarction in the Guinea Pig Heart
Background: Myocardial infarction (MI) is associated with adverse remodeling of the cardiac neurohumoral control systems as well as ventricular structure and function. The objective of this study was to determine whether chronic autonomic regulation therapy (ART) could attenuate MI stress-induced remodeling of cardiomyoctes, thereby preserving contractile function.
Methods: Guinea pigs were implanted with a vagus nerve stimulation (VNS) system on the right cervical vagus (n=6). Two weeks later, MI was produced by ligation of one coronary artery. The ART treatment group was stimulated at 20 Hz, 0.9 ± 0.2 mA pulse amplitude, with duty cycle of 14 s ON, 48 s OFF for 90 days and compared to time matched MI guinea pigs that received no VNS therapy (MI Control, n=6). Echo cardiograms were performed before MI and at 90 days post MI. At termination, the left ventricle was divided in 3 different sections (infarct, border and peripheral zones). Western blots were performed to determine the ratio of pGS/GS and pGSK-3β/GSK-3β, as well as the level of pro-apoptotic BAX protein.
Results: Left ventricular end systolic volume (LVESV) for MI controls increased 30% (p=0.027) and LV ejection fraction (EF) decreased 7% (p<0.001) at 90 days post MI, compared their baseline level. In the ART group, adverse remodeling of LV function as assessed by echo was mitigated; LVESV and LV EF at 90 days post MI were not different from baseline levels. A significant reduction in the p-GS/GS was detected after MI in both the necrotic and border zones. ART preserved this ratio at a control state. A pro-apoptotic state was established after MI with a threefold reduction in the p-GSK/GSK ratio and a twofold increase of the BAX protein level; both of these levels were preserved at levels comparable to the sham MI controls with ART.
Conclusion: Chronic ART after MI abolished adverse LV functional remodeling and promoted an anti-apoptotic state at the myocyte level.
- © 2013 by American Heart Association, Inc.