0059 : The involvement of a cocktail of amino acids in remote ischemic preconditioning induced cardioprotection in acute myocardial infarction

Background Remote ischemic preconditionning (RIPC) has emerged as an attractive therapeutic procedure to protect the heart against ischemia/reperfusion (I/R) injury. Despite strong evidences of the critical role played by circulating humoral mediators for signal transduction, their identities still remain unknown. Using a targeted metabolomic approach we previously identified Glycine (GLY) and Kynurenine (KYN) as potential mediators for RIPC induced cardioprotection in both rats and humans. Aim of the study this study sought to determine whether a treatment with GLY and KYN alone or in combination could mimic the cardioprotective effect of the RIPC. Methods Male Wistar rats, 8-10 weeks exposed to myocardial I/R were allocated to one of the following six groups: Myocardial Infarction (MI) , rats were subjected to myocardial I/R without any further intervention; RIPC+MI , four cycles of limb I/R were applied prior to the myocardial ischemia; Metabolites+ MI , with intraperitoneal (ip) injection of a combined GLY (0.5mg/g body weight) and KYN (0.3 mg/g body weight) 10 min before MI; Vehicle+MI , with ip injection of the vehicle 10 min before MI; GLY+MI , with ip injection of single dose of GLY 10 min before MI; and KYN+MI , with an ip injection of single dose of KYN 10 min prior to MI. Hearts were excised after 2h of reperfusion, the area at risk (AAR) and infarct size (AN) were measured after TTC staining. GLY and KYN plasma concentrations were determined by mass spectroscopy LC-MS/MS at 3 points of time: 15, 30 and 45 min after the ip injection. Results The metabolites blood assay showed a significant increase of both glycine and kynurenine in blood plasma 15 min after the intraperitoneal injection with a peak at 30 min. As compared to MI , both RIPC+MI and Metabolites+MI exhibited a smaller infarct size (AN/AAR=39.59±3.76% for Vehicle+MI vs. 27.15±4.47% for the Metabolites+MI group, and 42.49±2.42% for MI vs. 34.53±2.28% for the RIPC+MI , both p Kynurenine+MI vs. MI group; p =0.0018 and 33.24±2.30% in Glycine+MI , vs. MI, p=0.006 ). Conclusion We report that RIPC-induced cardioprotection may involve a cocktail of amino acids for signal transduction from the remote organ to the myocardium. The author hereby declares no conflict of interest