CardiothoracicRemote Perconditioning Reduces Myocardial Injury in Adult Valve Replacement: A Randomized Controlled Trial
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.
Section snippets
Patients Selection
This study was approved by our hospital research committee. Between July and October 2009, we recruited consecutive patients aged from 18 to 65 y with rheumatic heart valve disease. Exclusion criteria included infective endocarditis, previous cardiac surgery, and complications with diabetes, coronary artery disease, hypertension, or peripheral vascular disease affecting the lower limbs. Patients receiving aspirin, corticosteroids, angiotensin-converting enzyme inhibitors, or statin were
Patients' Demography and Intraoperative Data
Ninety-three patients were assessed for eligibility, of whom 12 patients were excluded: three congenital valve abnormalities; three infective endocarditis; two received angiotension-converting enzyme inhibitors; two combined with coronary artery bypass surgery, and two over 65 y old. Eighty-one patients were actually studied and randomized to three groups. The preoperative variables were comparable among the groups (Table 1). There was no significant difference with respect to cardiac ischemic
Discussion
This study is the first randomized controlled trial of remote perconditioning in clinical procedure. The major finding of this study is that three cycles of 4/4 min lower limb ischemic perconditioning significantly reduced cTnI peak level by 40% in adult valve replacement. In addition, only 25% of patients required defibrillation in the remote perconditioning group, while more than 50% patients received defibrillation in the control or remote preconditioning group. The idea of remote
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