0129: Pharmacological modulation of microparticle-mediated vascular response in a rat model of septic shock

Introduction Circulating procoagulant microparticles (MPs) take part in septic shock vascular dysfunction through pro-inflammatory and procoagulant detrimental effects. Aims were to study how circulating procoagulant MPs are involved in the vascular dysfunction of septic shock and to examine if the pharmacological modulation of MP could be beneficial. Methods In a first set of experiments, MPs were isolated from sham or septic rats obtained by cecal ligation and puncture, resuscitated and treated by activated protein C (aPC). Then, healthy recipients were inoculated with septic MPs and hemodynamic parameters were recorded during 4 hours. At the end of the record, blood and organs were harvested. Results Treating septic rats with aPC significantly reduced norepinephrine needs to reach the mean arterial pressure goal and leukocyte-derived MPs (6.2±2.1 vs 2.9±1.7 nM PhtdSer, p Conclusions During sepsis, MPs modulate the inflammatory response in cardiac and vascular tissues and contribute to septic hemodynamic dysfunction. Concentration, phenotype and properties of circulating MPs can be pharmacologically modulated. Indeed, aPC switches pro-inflammatory and hypotensive properties of septic MPs to beneficial and anti-inflammatory ones, contributing to the hemodynamic improvement.