Remote Perconditioning Reduces Myocardial Injury in Adult Valve Replacement: A Randomized Controlled Trial

Background

Remote perconditioning has been proved to reduce myocardial infarction and improve ventricular function in vivo. This study aims to determine the protection of remote perconditioning against cardiac reperfusion injury in patients undergoing valve replacement.

Methods

Eighty-one patients admitted for selective valve replacement were divided into three groups randomly. Control patients (con. n = 27) underwent sham placement of the tourniquet around the right thigh without inflation; the remote preconditioning group (pre. n = 26) received three cycles of 4/4 min right lower limb ischemia and reperfusion after induction of anesthesia, the limb ischemia was induced by the tourniquet inflated to 600 mmHg; the remote perconditioning group (per. n = 28) received the same stimulus immediately after aortic cross-clamping. Venous blood samples were obtained preoperatively, 5 min before declamping, 30 min, 4, 12, and 72 h after declamping for detecting troponin I (cTnI) concentration. The clinical data of inotrope requirement, drainage, ventilation. and intensive care time were routinely recorded.

Results

The remote perconditioning group had significantly lower release of cTnI 5 min before declamping (con. versus pre. versus per., 0.15 ± 0.10 versus 0.13 ± 0.08 versus 0.10 ± 0.04 ng/mL, P = 0.050) and 30 min after declamping (con. versus pre. versus per., 0.40 ± 0.24 versus 0.41 ± 0.40 versus 0.24 ± 0.13 ng/mL, P = 0.043). Less incidence of defibrillation were observed in the remote perconditioning groups.

Conclusions

Remote perconditioning, which is induced by transient lower limb ischemia after aortic cross-clamping, reduces myocardial injury over cardioplegia in adults undergoing selective valve replacement.

Introduction

Since Murry proposed the concept of ischemic preconditioning in 1986 [1], a large number of articles have focused on it and the definition has been extended to postconditioning [2]. Due to the disputed outcome of clinical researches and practical difficulties in delivering the stimulus directly to the heart, which is not favored by surgeons, ischemic conditioning has not been translated from bench to bedside. In the early 1990s, Przyklenk and his colleagues developed the idea of remote preconditioning for the first time [3]. They declared that brief ischemia of circumflex artery salvaged myocardium from subsequent sustained left anterior descending artery (LAD) occlusion. This phenomenon lends credence to the delivery of protective signal from a pretreated tissue or organ to another through circulating substrates or neural mechanism. It was definitely validated in a series of experiments showing that brief ischemia of kidney, intestine, or limb reduced extent of myocardial infarction 4, 5, 6. Especially, limb preconditioning, which is considered to be feasible, noninvasive, and as effective as local conditioning, is popular to practitioners [7].

As it is currently known, remote conditioning not only can be triggered before ischemic events of the heart, which is termed remote preconditioning; but can also be induced during and after cardiac ischemia, which is termed as remote per- and postconditioning, respectively [8]. Schmidt [9] demonstrated that brief limb ischemia during cardiac ischemia and before reperfusion provided significant protection against reperfusion injury and, thus, introduced a concept of remote perconditioning. Remote preconditioning has been proven to be protective in clinical settings 10, 11, 12; also there are studies that show benefit of remote postconditioning 13, 14; however, remote perconditioning is limited to animal study [9]. In the present study, we tested whether remote perconditioning, which was induced by brief limb ischemia promptly after aortic cross-clamping, could reduce myocardial injury in adults undergoing valvular surgery. Simultaneously, we examined whether remote pre- and perconditioning offered the same degree of protection.