Remote Ischemic Preconditioning for Cardioprotection in Patients Undergoing Cardiac Surgery: A Systemic Review

Abstract

A short period of sublethal ischemia can provide cardioprotection against ischemia/reperfusion injury. As direct application of ischemic to the heart is impractical, remote ischemic preconditioning (RIPC) is usually preferred. The mechanism through which the cardioprotective effect is transferred from the remote organ or tissue to the heart remains unclear. Neurogenic, hormonal, and systemic factors have been proposed. Although RIPC has been applied in clinic with different modes, its effect on major cardiac outcomes, especially among diabetic patients, is still controversial. Therefore, further studies are still needed to identify its exact role in clinical practice and also investigate more specific mechanisms. has been considered as more feasible and promising than IPC due to its non-invasiveness. RIPC utilizes transient ischemia and reperfusion of one vascular bed, organ or tissue away from the heart to precondition another vascular bed. It has been applied before the onset of sustained myocardial ischemia [5]. However, the effect of RIPC on clinical outcome among different patients is controversial [6-8]. The differences and complications of patient population involved or differences in the RIPC procedures or the timing of application in different studies may be possible explanations for the controversies observed. However, the major reason for the uncertainty of RIPC cardiopropection is likely the lack of a clear understanding of the mechanism RIPC. Definition and Differences of Conditionings IPC, RIPC and APC that are Applicable during Cardiac Surgery Ischemic preconditioning (IPC), defined as several brief periods of ischemia and reperfusion of the target organ before prolonged ischemia [9], is regarded as a protective means capable of resisting myocardial ischemia-reperfusion injury (IRI). During cardiac surgery such as coronary artery bypass surgery (CABG), coronary artery is inaccessible for IPC [9]. The alternative to IPC is remote ischemic precondition (RIPC), a noninvasive simple method, which is induced by several rounds of short-term remote organ (e.g. upper limbs) ischemia and reperfusion before prolonged myocardial ischemia [6,10-11]. There have been trials confirming that RIPC can significantly reduce cardiac specific enzymes troponin I (cTnI) [10] and cTnT [11] levels in the serum within 72 hours after surgery, as well as decrease myocardium infarct size [7] and promote post-operative patient recovery [12]. However, whether or not it can improve long term cardiovascular outcomes still remains controversial [7,13], despite that the beneficial effect of RIPC on new onset Myocardial Ischemia and Reperfusion Injury Myocardial ischemia is a major cause of myocardial injury and may result in myocardial infarction. Reperfusion therapies or interventions to restore blood flow to ischemic myocardium are needed to limit infarct size, but, return of blood flow can cause additional cardiac damage and complications which is known as reperfusion injury. Nevertheless, myocardium possesses adaptive mechanisms which can resist potentially lethal ischemia and reperfusion injury. Ischemic preconditioning (IPC), a short period of sublethal ischemia intervention prior to a prolonged ischemic event, was discovered over 30 years ago by Reimer and Murry, et al. [1,2] and was believed to be capable of providing myocardial protection against ischemia/reperfusion (I/R) injury. Although IPC is a reproducible cardioprotective intervention [3], it has not been fully translated into clinical practice. The major limitation of myocardial IPC is that it requires a protective stimulus to be applied to the heart directly, which is usually invasive with unpredictable adverse effect [4] and thus infeasible. Accordingly, remote ischemic preconditioning (RIPC)