Burban Mélanie, Meyer Grégory, Olland Anne, Séverac François, Yver Blandine, Toti Florence, Schini-Kerth Valérie, Meziani Ferhat, Boisramé-Helms Julie
*EA 7293 FMTS, University of Strasbourg, Strasbourg, France †Biophotonic anc Pharmacology Laboratory, UMR 7213, University of Strasbourg, Illkirch, France ‡EA 4278, University of Avignon, F84000 Avignon, France §Laboratory of Medical Biostatistics and Informatics, University of Strasbourg, Strasbourg, France ¶Group Method in Clinical Research, Public Health Unit, Strasbourg University Hospital, Strasbourg, France ||Medical Intensive Care Unit, Strasbourg University Hospital, Strasbourg, France.
Shock. 2016 Nov;46(5):549-556. doi: 10.1097/SHK.0000000000000624.
Enriching the diet with Omega-3 for several weeks improves myocardial resistance to ischemia-reperfusion (IR) in rats. However, patients with myocardial infarction requiring an emergency reperfusion cannot be pretreated with such a diet. The objective of our study was to describe the effects of an intravenous Omega-3 bolus before reperfusion in a rat model of myocardial IR.
In a rat model of acute myocardial IR, an intravenous Omega-3 bolus (EPA:DHA 6:1), associated or not with iodinated contrast media, was administered after a 30-min ischemia, before reperfusion. Hemodynamic parameters were assessed. Circulating procoagulant microparticles were phenotyped. Vascular and heart inflammation, superoxide anion, and nitric oxide were measured. Ex vivo vascular reactivity was performed with a pharmacological selective inhibitor of inductible nitric oxide synthase. Cardiac troponin I (cTn-I) plasma levels were measured.
Compared with untreated IR rats, an Omega-3 bolus before reperfusion significantly decreased the IR syndrome, improving mean arterial pressure (114 ± 9 vs. 61 ± 17 mmHg 4 h after reperfusion, P < 0.05) and carotid blood flow, and decreasing plasma cTn-I levels after revascularization. These beneficial effects may be due to improved ex vivo mesenteric resistance artery sensitivity to phenylephrine, endothelial protection assessed by decreased endothelial CD54 microparticle release (9.1 ± 2.5 vs. 4.8 ± 2.0 nM Eq PhtdSer, P < 0.05) and reduced vascular inflammation and oxidative stress.
In this rat model of myocardial IR, an intravenous Omega-3 bolus before reperfusion decreases IR-induced vascular failure and shock. These results open therapeutic perspectives as far as myocardial reperfusion process is concerned that deserve further explorations in humans.
数周内用ω-3丰富饮食可提高大鼠心肌对缺血再灌注(IR)的耐受性。然而,需要紧急再灌注的心肌梗死患者无法接受这种饮食预处理。我们研究的目的是描述在心肌IR大鼠模型中再灌注前静脉注射ω-3推注的效果。
在急性心肌IR大鼠模型中,于缺血30分钟后、再灌注前静脉注射ω-3推注(EPA: DHA 6:1),可联合或不联合碘化造影剂。评估血流动力学参数。对循环促凝微粒进行表型分析。测量血管和心脏炎症、超氧阴离子和一氧化氮。使用诱导型一氧化氮合酶的药理学选择性抑制剂进行离体血管反应性检测。测量血浆中心肌肌钙蛋白I(cTn-I)水平。
与未治疗的IR大鼠相比,再灌注前静脉注射ω-3推注可显著减轻IR综合征,改善平均动脉压(再灌注4小时后分别为114±9与61±17 mmHg,P<0.05)和颈动脉血流量,并降低血管重建后血浆cTn-I水平。这些有益作用可能归因于离体肠系膜阻力动脉对去氧肾上腺素的敏感性提高、通过内皮CD54微粒释放减少评估的内皮保护作用(9.1±2.5与4.8±2.0 nM Eq PhtdSer,P<0.05)以及血管炎症和氧化应激减轻。
在这个心肌IR大鼠模型中,再灌注前静脉注射ω-3推注可减轻IR诱导的血管功能衰竭和休克。就心肌再灌注过程而言,这些结果为治疗开辟了前景,值得在人类中进一步探索。