BackgroundRemote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. MethodsWe conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. ResultsA total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patie...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1413579

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery

Remote Ischemic Conditioning

Mitochondria have emerged as key participants in and regulators of myocardial injury during ischemia and reperfusion. This review examines the sites of damage to cardiac mitochondria during ischemia and focuses on the impact of these defects. The concept that mitochondrial damage during ischemia leads to cardiac injury during reperfusion is addressed. The mechanisms that translate ischemic mitochondrial injury into cellular damage, during both ischemia and early reperfusion, are examined. Next, we discuss strategies that modulate and counteract these mechanisms of mitochondrial-driven injury. The new concept that mitochondria are not merely stochastic sites of oxidative and calcium-mediated injury but that they activate cellular responses of mitochondrial remodeling and cellular reactions that modulate the balance between cell death and recovery is reviewed, and the therapeutic implications of this concept are discussed.

Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion: Implications for Novel Therapies

https://www.internationaljournalofcardiology.com/article/S0167-5273(14)01085-7/pdf

Remote preconditioning and major clinical complications following adult cardiovascular surgery: Systematic review and meta-analysis

A wealth of evidence has revealed that the heart can be “conditioned” and rendered less vulnerable to ischemia–reperfusion injury via the upregulation of endogenous protective signaling pathways. Three distinct conditioning strategies have been identified: (1) preconditioning, the phenomenon where b

Reduction of myocardial infarct size with ischemic "conditioning": physiologic and technical considerations.

Aims Transient ischaemia of non-vital tissue has been shown to enhance the tolerance of remote organs to cope with a subsequent prolonged ischaemic event in a number of clinical conditions, a phenomenon known as remote ischaemic preconditioning (RIPC). However, there remains uncertainty about the efficacy of RIPC in patients undergoing cardiac surgery. The purpose of this report is to describe the design and methods used in the "Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart)-Study". Methods We are conducting a prospective, randomized, double-blind, multicentre, controlled trial including 2070 adult cardiac surgical patients. All types of surgery in which cardiopulmonary bypass is used will be included. Patients will be randomized either to the RIPC group receiving four 5 min cycles of transient upper limb ischaemia/reperfusion or to the control group receiving four cycles of blood pressure cuff inflation/deflation at a dummy arm. The primary endpoint is a composite outcome (all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure) until hospital discharge. Conclusion The RIPHeart-Study is a multicentre trial to determine whether RIPC may improve clinical outcome in cardiac surgical patients.

Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study

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Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study