AimsWhole body periodic acceleration (pGz) is achieved with a motorized platform that moves the supine body with repetitive, sinusoidal head to foot motion. This increases pulsatile shear stress to the endothelium thereby activating endothelial nitric oxide synthase (eNOS) to produce increased release of nitric oxide (eNO). The current investigation was undertaken to determine whether or not pGz preconditioning can induce second window of protection (SWOP) cardioprotective affects in an in-vivo rat model of myocardial infarction. Main methodsRats received 1, 3 or 7 daily pGz treatments of 60minutes, or no pGz (CONT). Twenty-four hours after the last pGz treatment, ischemia reperfusion injury was produced by ligation of the left coronary artery (LCA) for 30minutes followed by 90minutes of reperfusion. Key findingsAll pGz preconditioned animals survived 90minutes. Three and 7days of pGz preconditioning reduced myocardial infarct size by 41 and 38% respectively, with better left ventricular function. Additionally, pGz preconditioning increased eNOS, p-eNOS, Akt and p-Akt, HSP70 and nNOS proteins. L-NAME (NOS inhibitor) or Wortmannin (PI3/Akt inhibitor) 15minutes prior to LCA ligation abolished pGz's cardioprotective effects. SignificancepGz preconditioning provides SWOP, with increased survival, infarct size reduction, and improved contractility, in part due to up regulation of HSP70 and the PI3/Akt/eNOS , which last at least 72hours.