Elsevier

The Lancet

Volume 370, Issue 9587, 18–24 August 2007, Pages 575-579
The Lancet

Articles
Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial

https://doi.org/10.1016/S0140-6736(07)61296-3Get rights and content

Summary

Background

Whether remote ischaemic preconditioning, an intervention in which brief ischaemia of one tissue or organ protects remote organs from a sustained episode of ischaemia, is beneficial for patients undergoing coronary artery bypass graft surgery is unknown. We did a single-blinded randomised controlled study to establish whether remote ischaemic preconditioning reduces myocardial injury in these patients.

Methods

57 adult patients undergoing elective coronary artery bypass graft surgery were randomly assigned to either a remote ischaemic preconditioning group (n=27) or to a control group (n=30) after induction of anaesthesia. Remote ischaemic preconditioning consisted of three 5-min cycles of right upper limb ischaemia, induced by an automated cuff-inflator placed on the upper arm and inflated to 200 mm Hg, with an intervening 5 min of reperfusion during which the cuff was deflated. Serum troponin-T concentration was measured before surgery and at 6, 12, 24, 48, and 72 h after surgery. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00397163.

Findings

Remote ischaemic preconditioning significantly reduced overall serum troponin-T release at 6, 12, 24, and 48 h after surgery. The total area under the curve was reduced by 43%, from 36·12 μg/L (SD 26·08) in the control group to 20·58 μg/L (9·58) in the remote ischaemic preconditioning group (mean difference 15·55 [SD 5·32]; 95% CI 4·88–26·21; p=0·005).

Interpretation

We have shown that adult patients undergoing elective coronary artery bypass graft surgery at a single tertiary centre could benefit from remote ischaemic preconditioning, using transient upper limb ischaemia.

Introduction

Several studies have shown that myocardial injury, as indicated by the release of perioperative cardiac enzymes, is associated with worse patient morbidity and mortality after coronary artery bypass graft surgery.1, 2, 3, 4, 5 One potential strategy for reduction of myocardial injury sustained during this surgery is ischaemic preconditioning, which describes the cardioprotection obtained from application of one or more non-lethal episodes of myocardial ischaemia and reperfusion before the index myocardial ischaemic event.6 However, since an ischaemic preconditioning protocol cross-clamps the aorta, this particular intervention is both invasive and impractical to apply.7, 8

A more amenable and less invasive approach to cardioprotection might be achieved by remote ischaemic preconditioning, whereby brief ischaemia in one region or organ protects distant tissue or organs from a sustained episode of ischaemia. In 1993, Przyklenk and colleagues9 showed that a brief circumflex artery occlusion could reduce the myocardial infarct size induced by the subsequent sustained occlusion of the left anterior descending artery. This notion was further advanced in subsequent studies which reported that brief ischaemia of non-cardiac tissue such as the kidney,10 the intestine,11 or skeletal muscle12 could also protect the heart against a subsequent myocardial infarction. Remote ischaemic preconditioning induced by transient ischaemia of one arm has been shown to protect the contralateral arm against endothelial dysfunction mediated by a sustained ischaemic episode.13, 14 This particular protocol has also modified myocardial gene expression by upregulation of cytoprotective genes and suppression of proinflammatory genes that are potentially involved in the pathogenesis of ischaemia-reperfusion injury.15, 16 Furthermore, it has been used to attenuate myocardial injury in a porcine model of coronary artery bypass graft surgery17 and in children undergoing corrective cardiac surgery for congenital heart disease.18

We aimed to assess whether this remote ischaemic preconditioning protocol is effective in reducing myocardial injury in adults with coronary artery disease undergoing elective coronary artery bypass graft surgery.

Section snippets

Patients

Between February, 2006, and February, 2007, we recruited consecutive adult patients with coronary artery disease referred for elective coronary artery bypass graft surgery. We excluded patients older than 80 years, those with unstable angina, left main stem disease, or hepatic, renal, or pulmonary disease, and those with peripheral vascular disease affecting the upper limbs. Additionally, patients taking the antidiabetic sulphonylurea, glibenclamide, were excluded since this agent has been

Results

Figure 1 shows the trial profile. 66 patients were assessed for eligibility, of whom 57 were actually recruited and randomly assigned to remote ischaemic preconditioning group (n=27) or control group (n=30). Table 1 shows baseline characteristics. There was no difference in the details of coronary artery bypass graft surgery between patients in both treatment groups (table 2). The time taken from the termination of the remote ischaemic preconditioning protocol to the first aortic cross-clamp

Discussion

Our study has shown that remote ischaemic preconditioning, mediated by transient upper limb ischaemia, can reduce troponin T in the perioperative period in adult patients undergoing elective coronary artery bypass graft surgery.

Several studies have shown that the release of troponin T,3, 4 troponin I,2, 5 and CK-MB1 is associated with poor short-term and long-term clinical outcomes after surgery. Lehrke and colleagues3 reported in a case series of 204 patients undergoing elective coronary

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