P2687Impact of cardiovascular risk factors on effectiveness of remote ischemic preconditioning in the setting of ischemia/reperfusion-injury in a langendorff heart model
Authors: Hidalgo Pareja L , Muessig J M , Nia A M , Masyuk M , Kelm M , Jung C 
Published: October 2019

Abstract

Introduction
Cardiovascular diseases are the most frequent cause of death in the western world. During myocardial infarction both, ischemia and reperfusion after therapeutic intervention cause myocardial damages, resulting in ischemia/reperfusion-injury (I/R-injury). Research therefore searches cardio protective interventions, aiming to reduce myocardial injury and following consequences such as heart failure. A promising method, named Remote Ischemic Preconditioning (RIPC), consists of transient local ischemia distant from the heart. Its cardio-protective effects were already proved in basic research but failed in clinical trials.

Purpose
The aim of the study is to examine the impact of cardiac risk factors like diabetes mellitus (DM) or age on effectiveness of RIPC in order to identify distinct groups of patients who might benefit from RIPC in the clinical setting and to reveal the effectiveness of cardioprotection delivered by plasma samples of these groups of patients.

Methods
RIPC (3 x 5 min arm ischemia, induced by an inflated blood pressure cuff) was performed on young and healthy volunteers and elderly patients with coronary heart disease with or without diabetes mellitus. Blood was taken before (Baseline) and 30 minutes after the intervention. The coronary system of murine hearts in a Langendorff heart model was perfused using dialysate from the human plasma obtained before and after RIPC. This was followed by 40 minutes of global ischemia. After 60 minutes of reperfusion left ventricular function was analysed. The infarct size was measured after 120 minutes reperfusion time using a TTC staining.

Results
Addition of dialysate of plasma obtained from healthy volunteers after RIPC to the coronary system of Langendorff perfused murine hearts significantly improved the recovery of left ventricular developed pressure (39±15.1 vs 26±8.5% of baseline levels, p=0.04) and reduced the infarct size (37.5±15.6 vs 21.2±11.4% of the ventricular volume, p=0.03) compared to baseline-dialysate treated controls. While plasma dialysate obtained from elderly patients with DM undergoing RIPC failed to show significant cardio protective effects of RIPC, murine hearts treated with plasma dialysate of elderly patients with coronary heart disease without diabetes after undergoing RIPC showed significant improvement of cardiac function (20±6.5 vs 24±7% of baseline levels, p=0.02) and infarct size (33.2±8.0 vs 11.1±2.5% of the ventricular volume, p=0.01).

Conclusion
The cardio-protective effect of RIPC on myocardial function and infarct size after I/R is influenced by diabetes but not by age or the presence of coronary heart disease. In consequence, RIPC might protect patients with coronary heart disease without DM but not diabetic patients from cardiac I/R injury. This important finding potentially explains why RIPC yielded promising results in various basic science experiments but failed to show cardio protective effects in clinical trials.

Acknowledgement/Funding
Forschungskommission of the Faculty of Medicine of the Heinrich-Heine-University Düsseldorf