Ringer's solution but not hydroxyethyl starch or modified fluid gelatin enhances platelet microvesicle formation in a porcine model of septic shock†

Abstract

Sepsis is associated with volume deficit and clotting system activation. Platelet activation in sepsis results in an increased formation of microvesicles, which in turn, have been associated with increased mortality. We hypothesized an effect of different volume replacement solutions on platelet-derived microvesicle formation in septic shock. Anaesthetized, mechanically ventilated and multi-catheterized pigs received 1 g kg(-1) body weight faeces into the abdominal cavity to induce sepsis and were observed over 8 h. Five animals in each group received volume replacement therapy with modified fluid gelatin 4% or 8% (MFG4%, MFG8%), 6% hydroxyethylstarch (HES) 200/0.5 or Ringer's solution (RS) to maintain a central venous pressure of 12 mm Hg. Flow cytometry was used for determination of microvesicles before induction of sepsis (baseline) and after 8 h. Platelets and microvesicles were identified with an anti-platelet monoclonal Ab and a secondary antibody. Microvesicles were determined as the smallest 1-3% positive cells in forward scatter. Intergroup comparisons were performed using Wilks-Lambda and Ryan-Einot-Gabriel-Welsh F-test. Differences within groups were compared using a two-tailed Student's t-test. Baseline values were considered as 100%. While microvesicle formation was reduced in HES (73 (sd 19)%), MFG4% (63 (41)%) and MFG8% groups (53 (17)%), an increase in the RS-group (210 (121)%) was observed. Eight hours after induction of sepsis, formation of microvesicles was significantly higher in the RS group compared to all colloid-treated groups. In this porcine septic shock model the formation of platelet-derived microvesicles was significantly increased by volume replacement with Ringer's solution in comparison to colloid solutions.