Abstract 15777: Preconditioning With Whole Body Periodic Acceleration (pGz) Protects Cardiomyocytes From Hypoxia-Reoxygenation Injury
Hypoxia and Reoxygenation (H-R) injury of the heart induces increase in diastolic Ca2+ ([Ca2+]d, and reactive oxygen species (ROS) leading to cellular death and myocardial dysfunction. pGz is the repetitive head-foot motion of the body inducing pulsatile shear stress, activating endothelial nitric oxide synthase (eNOS) to produce small quantities of eNO. eNO is cardioprotective and active in varied signaling pathways. We showed that preconditioning with pGz (pre-pGz) decreased myocardial injury from focal myocardial injury (MI) and cardiac arrest and increases the level and activity of endogenous antioxidants
Hypothesis: pre-pGz confers cardioprotection in a cellular model of H-R injury.
Methods: Mice (n=30) were randomized to pGz (f=480cpm, Gz 3.0mt/sec2,1 hr /d for 8 days) or none (CONT). Cardiomyocytes were isolated and exposed to 45 min hypoxia, followed by 15min reoxygenation (H-R). Resting membrane potentials (Vm) and [Ca2+]d were measured with microelectrodes. Intracellular ROS and glutathione peroxidase activity (GPx) were measured during normoxia and after H-R. In a separate group of mice, L-NAME was administered for 5 days along with pre-pGz prior to H-R (L-NAME+pGz+H-R).
Results: Resting membrane potentials (Vm) were decreased by H-R and restored by pre-pGz. A 15x (fold) increase in [Ca2+]d and 5x increase in ROS production occurred in H-R that was blunted by pre-pGz. GPx activity was decreased but pre-pGz restored it. Pretreatment with L-NAME to pre-pGz animals abolished the effects of pGz. (FigureM±SD***p<0.001)
Conclusion: Cardioprotection by pGz from H-R injury is in part due to a decrease in membrane depolarization, improved Ca2+ homeostasis and reduction of ROS as well as increasing the level and activity of antioxidants. Such benefits are partially mediated via NO pathway. pGz is a novel, method of eliciting cardioprotection in hypoxic injury.
Author Disclosures: J.R. Lopez: None. J. Kolster: None. A. Uryash: None. F. Altamirano: None. J.A. Adams: Ownership Interest; Modest; Stock options totaling < $10,000.
- © 2015 by American Heart Association, Inc.