Anaesthetics and remote ischaemic preconditioning: do not stop the music, despite a (yet) unhappy marriage

Abstract

Remote ischaemic preconditiong (RIPC), at least in the context of cardioprotection during heart surgery, has arrived at an apparent deadlock.Following numerous laboratory investigations demonstrating smaller areas of myocardial infarction following RIPC (for review, see [6]), proof of principle studies revealing lesser postoperative cardiac troponin concentrations as well as smaller clinical studies both with positive or negative results [3,[11][12][13], a larger monocentric trial had demonstrated not only significantly decreased postoperative cardiac troponin concentrations but also a significant reduction of all-cause mortality and MACCE rates as secondary end points with intermediate time follow-up [23]. This indicated less myocardial damage following RIPC with repetitive left upper arm ischemia/reperfusion following coronary artery bypass graft (CABG) surgery under isoflurane anaesthesia. Recently, however, two large multicenter studies, the RIPHeart and ERRICA trials, failed to show any positive effects on troponin concentrations and clinical end points, including mortality [4,16]. This resembles the situation with ischaemic preconditioning by intermittent coronary artery occlusion which never became a clinical routine [7], and leaves behind in reasonable frustration and disappointment both RIPC investigators and their clinician audience. Accordingly, it is clear now that RIPC is not an all purpose, easily implemented magic drink protecting all cardiac surgical patients and ensuring their longevity like a sip from the Holy Grail. In fact, the area under the curve of postoperative troponin concentrations, while likely reflecting cardiomyocyte injury during aortic crossclamping and subsequent reperfusion, is unlikely to strictly mirror clinical benefits for a patient and the mechanisms reflecting regional cardiac ischaemia/reperfusion in the awake state, such as during coronary stent interventions. However, it is premature to drop the final curtain in the RIPC theater. Rather, do not stop the music for a variety of reasons.First, let us not forget that the ultimate goal of RIPC research is not so much the efficacy of organ protection by simply blowing up blood pressure cuffs, perhaps giving physicians a less technical face and a long missed touch to treat by more natural means. Rather, we are only ready for prime time when the unique molecular downstream mechanism(s) of RIPC and their pathways have been solidly identified. Only then will we be able to mimic RIPC pharmacologically and with greater efficacy, likely yielding broad clinical applications. While RIPC mechanisms have not yet been identified in detail and there is evidence for a variety of humoral and neural pathways [1,[6][7][8]19], scientific troops are bulleyeing this target closer and closer, effectively encircling potential mechanisms down to the mitochondria. Accordingly, there still is hope for a magic pill or injection, e.g., mitochondrial potassium channel agonists, so stay tuned and listen to the music.Second, there is reason to look criti...