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Introduction: 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., Methods: 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., Results: 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., Conclusions: 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.

Background and Aims: Lipid emulsions for parenteral nutrition interfere with immunity and may alter the cell plasma membrane and microparticle release, thus modulating their biological effects. Our aim was to evaluate the effect of two lipid emulsions for parenteral nutrition containing either a mixture of long- and medium-chain triglycerides (LCTs and MCTs) or LCTs only, to assess their role on microparticle release and acute inflammation during septic shock in rats., Methods and Results: Septic rats (cecal ligation and puncture) and sham rats were infused with 5% dextrose or a lipid emulsion during 22 h. After 18 h, rats were resuscitated during 4 h and hemodynamic parameters monitored. Circulating microparticles and their phenotype were measured by prothrombinase assay; heart and aorta were collected for Western blotting and electron paramagnetic resonance measurements. No significant effect of lipid emulsions was observed in sham rats. In septic rats, norepinephrine requirements were increased in MCT/LCT-infused rats compared with 5% dextrose- or LCT-infused rats (2.7 ± 0.2 vs. 1.9 ± 0.8 and 1.2 ± 0.3 μg/kg per minute, respectively; P < 0.05) with increased procoagulant microparticle generation (38.6 ± 5.8 vs. 18.8 ± 3.1 and 19.2 ± 3.0 nM equivalent phosphatidylserine [Eq PhtdSer]; P < 0.05), leukocyte- (17.4 ± 3.5 vs. 7.7 ± 1.8 and 6.0 ± 1.1 nM Eq PhtdSer; P < 0.05), platelet- (13.9 ± 2.5 vs. 4.4 ± 0.7 and 5.4 ± 1.3 nM Eq PhtdSer; P < 0.05), and endothelial-derived microparticles (16.9 ± 3.6 vs. 6.4 ± 1.4 and 5.6 ± 0.8 nM Eq PhtdSer; P < 0.05). The mixture of MCTs/LCTs significantly increased cardiac and vascular nitric oxide and superoxide anion production, phosphorylated IκB, and cyclooxygenase 2 expression compared with the lipid emulsion containing only LCTs., Conclusions: Compared with 5% dextrose, MCT/LCT supplementation during septic shock in rats induced deleterious effects with increased inflammation and cell activation, associated to vascular hyporeactivity. During septic shock, LCT supplementation seemed to be neutral compared with 5% dextrose infusion.

Objective: Microparticles (MPs) are membrane vesicles with procoagulant and proinflammatory properties released during cell activation and might be potentially involved in the pathophysiology of septic shock. This study was designed to assess the effects of MPs from septic origin on the systemic hemodynamics as well as on the inflammatory, oxidative, and nitrosative stresses., Design: A prospective, randomized, controlled experimental study with repeated measurements., Setting: Investigational animal laboratory., Subjects: Forty healthy rats were randomly allocated to three groups: 10 animals inoculated with MPs isolated from control rats (cMPs), 15 animals inoculated with MPs isolated from sham rats (shMPs), and 15 animals inoculated with MPs isolated from rats with peritonitis (sMPs)., Interventions: Rats were anesthetized, mechanically ventilated, and infused with the same amount of cMPs, shMPs, or sMPs. We measured the heart rate, mean arterial pressure, carotid artery, and portal vein blood flows. Hemodynamic parameters were recorded during 7 hours, and then animals were killed. Aorta and heart were harvested for further in vitro tissue analyses., Measurements and Main Results: 1) The cellular origin (phenotype) but not the circulating concentration of MPs was different in septic rats, characterized by a significant increase in leukocyte-derived MPs. 2) sMPs but not cMPs or shMPs decreased mean arterial pressure without any effect on carotid artery and portal vein blood flows. 3) Rats inoculated with sMPs exhibited an increase in superoxide ion production and nuclear factor kappa B activity, overexpression of inducible nitric oxide synthase with subsequent nitric oxide overproduction and decrease in endothelial nitric oxide synthase activation., Conclusions: Rats with sepsis induced by peritonitis exhibited a specific phenotype of MPs. Inoculation of sMPs in healthy rats reproduced hemodynamic, septic inflammatory patterns, associated with oxidative and nitrosative stresses.