Autonomic imbalance in cardiac surgery: A potential determinant of the failure in remote ischemic preconditioning

Remote ischemic preconditioning (RIPC) is a cardioprotective strategy against myocardial damage by ischemia-reperfusion. Many in-vivo and ex-vivo animal researches have demonstrated that RIPC decreases significantly the ischemia-reperfusion myocardial damage, by up to 58% in isolated rat heart. Cardiac artery bypass graft surgery (CABG) is a clinical model of myocardial ischemia-reperfusion and a clinical potential application to RIPC. However, although RIPC has shown successful results in experimental studies, clinical trials on CABG have failed to demonstrate a benefit of RIPC in humans. Strikingly, the main proposed factors associated with this translational failure also impair the balance of the autonomic nervous system (ANS), which has shown to play a key role in RIPC cardioprotection in animal models. Comorbidities, chronic pharmacological treatment and anesthesic drugs - common conditions in CABG patients - cause an ANS imbalance through parasympathetic activity decrement. On the other hand, ANS and specially the parasympathetic branch are essentials to get cardioprotection by RIPC in animal models. Consequently, we propose that ANS imbalance in CABG patients would explain the failure of RIPC clinical trials. Whether our hypothesis is true, many patients could be benefited by RIPC: a cheap, simple and virtually broad-available cardioprotective maneuver. In this paper we discuss the evidence that support this hypothesis and its clinical implications.