Detrimental hemodynamic and inflammatory effects of microparticles

Introduction

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 [1, 2]. The present study was designed to assess the effects of MPs from septic origin on systemic hemodynamics as well as on the inflammatory, oxidative and nitrosative stresses.

Methods

We designed a prospective, randomized, controlled experimental study with repeated measurements. 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). Rats were anesthetized, mechanically ventilated and were infused with the same amount of cMPs or shMPs or sMPs. We measured the heart rate, mean arterial pressure, carotid artery blood flow and portal vein blood flow. Hemodynamic parameters were recorded during 7 hours, and then animals were sacrificed. The aorta and heart were harvested for further in vitro tissue analyses.

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 the 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 NF-κB activity, overexpression of inducible NO synthase with subsequent NO overproduction and decrease in endothelial NO synthase activation.

Conclusion

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.