Abstract 119: Cardioprotective Effects of Whole Body Periodic Acceleration (pGz) on Hypoxia-Induced Injury of Cardiac Myocytes
Intracellular calcium homeostasis and its derangements are key determinants of hypoxic cellular injury in many cells and particularly in cardiomyocytes. Whole body periodic acceleration (pGz) is the repetitive, sinusoidal motion to the horizontally positioned body, which induces pulsatile shear stress on the endothelium, stimulating release of endothelial-derived nitric oxide (eNO), prostaglandin-E2, prostacyclin, tissue plasminogen activator, and adrenomedullin. eNO modulates or closes the sarcolemmal and/or RyR2 Ca2+channels. pGz has been shown to induce preconditioning and is cardioprotective in animal models of ischemia reperfusion injury. We hypothesized that pGz preconditioning may modulate depolarization and intracellular calcium handling in response to hypoxia.
Methods: Mice (n=30) were randomized to receive pGz (1 hr daily for 8 days) or none (CONT). Cardiac myocytes were isolated, resting membrane potentials (Vm), and intracellular Ca2+ concentration ([Ca2+]i) measured using Ca2+ selective microelectrodes under normoxic conditions, after exposure to 30 min severe hypoxia/glucose deprivation, followed by reoxygenation.
Results: Vm did not differ between the two groups. Hypoxia induced a 21% and 13% depolarization of Vm in CONT and pGz, respectively. [Ca2+]i overload secondary to hypoxia and reoxygenation was markedly decreased by pGz (-50%). L-NAME given orally with pGz abrogated its protective effects on cardiomyocytes. Thus, protection by pGz from hypoxia injury on cardiomyocytes is in part due to improved Ca2+ homeostasis that decreases the magnitude of membrane depolarization and [Ca2+]i overload with the latter in part mediated via the nitric oxide pathway. pGz is a novel, non-invasive method of eliciting cardioprotection in hypoxic injury. Data are mean ±SD † p < 0.01 vs. CONT
- © 2011 by American Heart Association, Inc.