Preconditioning but not postconditioning treatment with resveratrol substantially ameliorates post-resuscitation myocardial dysfunction through the PI3K/Akt signaling pathway

Post-resuscitation myocardial dysfunction (PRMD) is a severe complication that arises in patients after cardiac arrest (CA). However, there are no safe or effective treatment strategies that are currently available to treat these patients. In the present study, it was investigated whether resveratrol administration could inhibit myocardial nitrative stress to alleviate PRMD. CA was induced in Sprague-Dawley rats by trans-oesophageal alternating electrical stimulation, followed by cardiopulmonary resuscitation. Rats were then randomly divided into a preconditioning or a postconditioning group. Left ventricular function (+dP/dt(max) and -dP/dt(min)) was recorded for 4 h after the return of spontaneous circulation (ROSC), after which the animals were euthanized. Myocardial nitrative stress was analysed using enzyme-linked immunosorbent assay, western blotting and immunohistochemistry. Wortmannin (a PI3K inhibitor) was used to investigate the involvement of the PI3k/Akt signalling pathway in the cardio-protective activity of resveratrol. After ROSC, resveratrol improved PRMD compared to the vehicle control; however, resveratrol administration significantly improved PRMD in the preconditioning group compared to the postconditioning group. Likewise, resveratrol preconditioning significantly decreased the expression of iNOS and nitrotyrosine in rat hearts but did not significantly ameliorate myocardial nitrative stress. Wortmannin partially inhibited the protective effect of resveratrol preconditioning and resulted in the deterioration of cardiac function and increase in iNOS and nitrotyrosine levels. Resveratrol preconditioning could alleviate PRMD by inhibiting myocardial nitrative stress. The PI3K/Akt signalling pathway may be partially involved in the process.