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

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• 作者：Oussama Bakhta¹ ; ^{o.bakhta@outlook.com" class="auth_mail" title="E-mail the corresponding author} ; Juan Manuel Chao De La Barca² ; Delphine Mirebeau-Prunier² ; Sophie Tamareille¹ ; Gilles Simard² ; Cé ; dric Gadras² ; Pascal Reynier² ; Fabrice Prunier¹
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：220
• 全文大小：93 K

文摘

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.

d="absSec_2">Aim of the study

d="spar0010">this study sought to determine whether a treatment with GLY and KYN alone or in combination could mimic the cardioprotective effect of the RIPC.

d="absSec_3">Methods Male

d="spar0015">Wistar rats, 8-10 weeks exposed to myocardial I/R were allocated to one of the following six groups: dFont">Myocardial Infarction (MI), rats were subjected to myocardial I/R without any further intervention; dFont">RIPC+MI, four cycles of limb I/R were applied prior to the myocardial ischemia; dFont">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; dFont">Vehicle+MI, with ip injection of the vehicle 10 min before MI; dFont">GLY+MI, with ip injection of single dose of GLY 10 min before MI; and dFont">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.

d="absSec_4">Results

d="spar0020">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 dFont">MI, both dFont">RIPC+MI and dFont">Metabolites+MI exhibited a smaller infarct size (AN/AAR=39.59±3.76% for dFont">Vehicle+MIvs. 27.15±4.47% for the dFont">Metabolites+MI group, and 42.49±2.42% for dFont">MIvs. 34.53±2.28% for the dFont">RIPC+MI, both p<0.05). Kynurenine injection alone and Glycine injection alone significantly decreased infarct size (AN/AAR=27.70±2.53% in dFont">Kynurenine+MIvs.dFont">MI group; p=0.0018 and 33.24±2.30% in dFont">Glycine+MI, vs.dFont">MI,p=0.006).

d="absSec_5">Conclusion

d="spar0025">We report that RIPC-induced cardioprotection may involve a cocktail of amino acids for signal transduction from the remote organ to the myocardium.

d="spar1005">The author hereby declares no conflict of interest