The Effect of Remote Ischemic Conditioning and Glyceryl Trinitrate on Perioperative Myocardial Injury in Cardiac Bypass Surgery Patients: Rationale and Design of the ERIC‐GTN Study

Abstract

Remote ischemic conditioning (RIC) using transient limb ischemia/reperfusion has been reported to reduce perioperative myocardial injury in patients undergoing coronary artery bypass grafting and/or valve surgery. The role of intravenous glyceryl trinitrate (GTN) therapy administered during cardiac surgery as a cardioprotective agent and whether it interferes with RIC cardioprotection is not clear and is investigated in the ERIC-GTN trial (http://www.clinicaltrials.gov: NCT01864252). The ERIC-GTN trial is a single-site, doubleblind, randomized, placebo-controlled study. Consenting adult patients (age > 18 years) undergoing elective coronary artery bypass grafting ± valve surgery with blood cardioplegia will be eligible for inclusion. Two hundred sixty patients will be randomized to 1 of 4 treatment groups following anesthetic induction: (1) RIC alone, a RIC protocol comprising three 5-minute cycles of simultaneous upper-arm and thigh cuff inflation/deflation followed by an intravenous (IV) placebo infusion; (2) GTN alone, a simulated sham RIC protocol followed by an IV GTN infusion; (3) RIC + GTN, a RIC protocol followed by an IV GTN infusion; and (4) neither RIC nor GTN, a sham RIC protocol followed by IV placebo infusion. The primary endpoint will be perioperative myocardial injury as quantified by the 72-hour area-under-the-curve serum high-sensitivity troponin T. The ERIC-GTN trial will determine whether intraoperative GTN therapy is cardioprotective during cardiac surgery and whether it affects RIC cardioprotection.

Remote Ischemic Conditioning in Cardiovascular Surgery

“…We need better, more focused trials that explicitly avoid propofol anesthesia and concomitant valve surgery and also observe all other established confounders, such as sulfonylureas 30 and possibly nitrates. 33,34 The potential benefit from remote ischemic conditioning is great as seen from all available studies in patients with acute myocardial infarction, 7,35 and we must work hard to make such potential protection available for clinical practice in patients undergoing cardiovascular surgery. The protection from remote ischemic conditioning may relate not only to the heart but also to other organs suffering from cardiovascular surgery such as the kidneys, 9,36 given that remote conditioning is a systemic response.…”

9th Hatter Biannual Meeting: position document on ischaemia/reperfusion injury, conditioning and the ten commandments of cardioprotection

“…Therefore, despite the neutral outcomes of RIPHeart and ERICCA, important questions remain unanswered in the context of cardiac surgery and the optimal anaesthetic management in the pre-, peri- and post-operative phases. Moreover, various peri-operative anaesthetic management strategies, from propofol anaesthesia to the administration of nitric oxide donors [e.g., intravenous glyceryl tri-nitrate (GTN) [ 42 ]; currently prospectively investigated in the ERIC-GTN trial [ 26 ]], require systematic careful investigation. In the presence of a cocktail of anaesthetic agents that may both inhibit canonical conditioning and are themselves cardioprotective, it is perhaps unsurprising that the demonstration of additional protection has become extremely difficult and perhaps also unnecessary.…”

Co‐morbidities and co‐medications as confounders of cardioprotection—Does it matter in the clinical setting?

“…In a retrospective analysis of another study, nitroglycerin did not interfere with protection, as determined from troponin release, by RIC (Kleinbongard, Thielmann et al, 2013). An ongoing prospectively designed, randomized controlled trial “Effect of RIC and Glyceryl Trinitrate on Perioperative Myocardial Injury in Cardiac Bypass Surgery Patients (ERIC‐GTN trial)” (Hamarneh et al, 2015) aims to resolve this controversy.…”