Cardioprotective Properties of Humoral Factors Released after Remote Ischemic Preconditioning in CABG Patients with Propofol-Free Anesthesia-A Translational Approach from Bedside to Bench.

Katharina Feige,Giovanna Lurati Buse,Patrick Maddison,Martin Stroethoff,Milena Gude,Carolin Torregroza,Ragnar Huhn,Markus W Hollmann,Sebastian Roth

doi:10.3390/jcm11051450

Abstract

The cardioprotective effect of remote ischemic preconditioning (RIPC) is well detectable in experimental studies but not in clinical trials. Propofol, a commonly used sedative, is discussed to negatively influence the release of humoral factors after RIPC. Further, results from experimental and clinical trials suggest various comorbidities interact with inducible cardioprotective properties of RIPC. In the present study, we went back from bedside to bench to investigate, in male patients undergoing CABG surgery, whether (1) humoral factors are released after RIPC during propofol-free anesthesia and/or (2) DM interacts with plasma factor release. Blood samples were taken from male patients with and without DM undergoing CABG surgery before (control) and after RIPC (RIPC). To investigate the release of cardioprotective humoral factors into the plasma, isolated perfused hearts of young rats (n = 5 per group) were used as a bioassay. The hearts were perfused with patients’ plasma without (Con) and with RIPC (RIPC) for 10 min (1% of coronary flow) before global ischemia and reperfusion. In additional groups, the plasma of patients with DM was administered (Con DM, RIPC DM). Infarct size was determined by TTC staining. Propofol-free RIPC plasma of male patients without DM showed an infarct size of 59 ± 5% compared to 61 ± 13% with Con plasma (p = 0.973). Infarct sizes from patients with DM showed similar results (RIPC DM: 55 ± 3% vs. Con DM: 56 ± 4%; p = 0.995). The release of humoral factors into the blood after RIPC in patients receiving propofol-free anesthesia undergoing CABG surgery did not show any cardioprotective properties independent of a pre-existing diabetes mellitus.

Highlights

In an experimental in vivo rat study, we demonstrated that infarct size reduction of remote ischemic preconditioning (RIPC) was abolished in the aged rat heart, whereas cardioprotection was fully present in the young rat [27]
The aim of the study was to focus on the presumed confounding factors, propofol and diabetes mellitus, discussed in clinical trials to abolish the protective effects of RIPC
The results of our study demonstrate that RIPC in patients undergoing CABG surgery with propofol-free anesthesia does not confer cardioprotection

Summary

Introduction

The resupply of coronary blood flow itself provokes ischemia-reperfusion injury (I/R), restraining the outcome of the reperfusion-intervention [2]. In the experimental setting, conditioning strategies induced ischemically (e.g., remote ischemic preconditioning (RIPC)) or pharmacologically have been shown to cause strong cardioprotection [3]. Translation of these experimental strategies into the clinical routine is still challenging and has yet failed to be successful [4]; considering the majority of large clinical trials demonstrate no detectable benefit for patient’s outcome [5,6]. The lack of transferability is partly caused by the invasiveness of ischemic-induced stimuli, which is only attainable in cardiac surgery or during interventional therapy.

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