A comparison between ischemic preconditioning, intermittent cross-clamp fibrillation and cold crystalloid cardioplegia for myocardial protection during coronary artery bypass graft surgery

Teoh, Lay Kheng

doi:10.1016/s0967-2109(02)00007-8

Cited by 33 publications

(19 citation statements)

References 17 publications

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“…Meanwhile, no study has ever truly shown that remote preconditioning of human myocardium is at all feasible. Indeed, there are many studies on human myocardium showing that ischaemic preconditioning can be elicited in experimental conditions, and protects against standardised ischaemic and reperfusion insult [22][23][24]. The same was shown with various forms of pharmacological preconditioning [25][26][27][28].…”

Section: Discussionmentioning

confidence: 85%

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

et al. 2018

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A b s t r a c tBackground: Remote preconditioning has been shown to be a potent protective phenomenon in many animals. Several studies aimed to demonstrate it was feasible in humans by trying to show its protective effect during cardiac surgery. Of these, some small studies and one larger trial were positive while two other bigger studies showed no effectiveness of remote preconditioning as assessed by levels of postoperatively released cardiac markers. Recently, two large clinical trials also failed to prove the benefit of remote preconditioning in cardiac surgery. No study showed that remote preconditioning actually increases resistance of human myocardium to standardised ischaemic and reperfusion stimulus in experimental settings. In animal studies, remote preconditioning was shown to improve mitochondrial function and structure, but such data on human myocardium are scarce. Aim:The aim of the study is to determine whether remote preconditioning protects human myocardium against ischaemia-reperfusion injury in both in vivo and in vitro conditions. Methods:The trial is designed as a single-centre, double-blinded, sham-controlled trial of 120 patients. We randomise (1:1) patients referred for coronary artery bypass grafting for stable coronary artery disease to remote preconditioning or "sham" intervention. The remote preconditioning is obtained by three cycles of 5 min inflation and 5 min deflation of a blood pressure cuff on the right arm. Postoperative course including myocardial enzymes profile will be analysed. Moreover, in the in-vitro arm the clinically preconditioned myocardium will be assessed for function, mitochondria structure, and mitochondria-dependent apoptosis. The informed consent of all patients is obtained before enrolment into the study by the investigator. The study conforms to the spirit and the letter of the declaration of Helsinki. Results and conclusions:In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the effect can be confirmed in a controlled experimental setting. The study might therefore indicate future directions in trials of clinical implementation of remote preconditioning. INTRODUCTIONNo experimental study showed that human myocardium can be remotely preconditioned against standardised ischaemic/hypoxic insult. We aim to remove this major knowledge gap by applying remote preconditioning to the patient and studying ex-vivo the myocardium obtained thereafter. We assume that we will be able to show that remote preconditioning by brief periods of ischaemia of the arm protects segments of human right atrial appendage myocardium subjected to simulated hypoxia and reoxygenation in-vitro.This proof of principle is crucial. In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the e...

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Section: Discussionmentioning

confidence: 85%

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

et al. 2018

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“…Although early studies using classical IP reported reduced troponin release, 11,12 improvement in high-energy phosphate conservation and reduced inotrope requirements, these effects were replicated in some but not all studies. [13][14][15][16] The clinical effect was less obvious and in some reports detrimental, 17 and this frustrated the use of classic IP as a surgical myocardial protective adjunct.…”

Section: Discussionmentioning

confidence: 99%

Remote Ischemic Preconditioning in Human Coronary Artery Bypass Surgery

et al. 2010

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“…The study cohorts were only small, but most of these studies revealed an infarct size reduction, that is, less injury ( Figure 1). [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] Some of these small studies looked at short-term clinical outcome as secondary end point, and either no effect or a reduction of postoperative arrhythmias, 55,63 need for inotropic support, 49,52,55,59,63 and intensive care unit stay 52 were reported (Table 1). Preinfarction angina may or may not be a correlate of ischemic preconditioning, but because of its nature, only retrospective associative analyses are available.…”

Section: Ischemic Preconditioningmentioning

confidence: 99%

Time to Give Up on Cardioprotection?

Heusch

Rassaf

2016

Circulation Research

176

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Abstract:The mortality from acute myocardial infarction (AMI) remains significant, and the prevalence of postmyocardial infarction heart failure is increasing. Therefore, cardioprotection beyond timely reperfusion is needed. Conditioning procedures are the most powerful cardioprotective interventions in animal experiments. However, ischemic preconditioning cannot be used to reduce infarct size in patients with AMI because its occurrence is not predictable; several studies in patients undergoing surgical coronary revascularization report reduced release of creatine kinase and troponin. Ischemic postconditioning reduces infarct size in most, but not all, studies in patients undergoing interventional reperfusion of AMI, but may require direct stenting and exclusion of patients with >6 hours of symptom onset to protect. Remote ischemic conditioning reduces infarct size in patients undergoing interventional reperfusion of AMI, elective percutaneous or surgical coronary revascularization, and other cardiovascular surgery in many, but not in all, studies. Adequate dose-finding phase II studies do not exist. There are only 2 phase III trials, both on remote ischemic conditioning in patients undergoing cardiovascular surgery, both with neutral results in terms of infarct size and clinical outcome, but also both with major problems in trial design. We discuss the difficulties in translation of cardioprotection from animal experiments and proof-ofconcept trials to clinical practice. Given that most studies on ischemic postconditioning and all studies on remote ischemic preconditioning in patients with AMI reported reduced infarct size, it would be premature to give up on cardioprotection. (Circ Res. 2016;119:676-695.

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A comparison between ischemic preconditioning, intermittent cross-clamp fibrillation and cold crystalloid cardioplegia for myocardial protection during coronary artery bypass graft surgery

Cited by 33 publications

References 17 publications

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

Remote Ischemic Preconditioning in Human Coronary Artery Bypass Surgery

Time to Give Up on Cardioprotection?

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