HEM-2: BENEFICIAL THERAPEUTIC EFFECT OF AN APOPTOTIC PERIPHERAL BLOOD MONONUCLEAR CELLS SECRETOME (APOSEC) SUPPLEMENTED RESUSCITATION AFTER HEMORRHAGIC TRAUMATIC SHOCK IN RATS.

INTRODUCTION: Hemorrhagic traumatic shock (HTS) and reperfusion is often associated with general inflammatory response and organ dysfunction. Recent preclinical studies have shown that APOSEC exerts cytoprotective and/or immunomodulating effects. We evaluated the therapeutic potential of APOSEC in a HTS model in rats.

METHODS: Rats were subjected to HTS (MAP 30-35 mmHg until decompensation) and a resuscitation protocol that includes a prehospital restrictive reperfusion (30 ml/kg/h, MAP maintained at 50-55 mmHg for 40 min) followed by an adequate reperfusion phase (75 ml/kg/h over 60 min, MAP to baseline). 20 minutes after onset of reperfusion, animals received either APOSEC (n = 14) or vehicle (n = 16) intravenously. Blood samples were obtained at baseline, end of resuscitation (EOR), 24 and 48 h after shock and survival was followed for 28 days.

RESULTS: APOSEC treatment attenuated apoptosis reflected by plasma histone release up to 24 h (p < 0.003), and modulated the immune response reflected in IL-10 (decrease by 26% at EOR) compared to vehicle group (p < 0.01). Changes in IL-6 and MCP-1 were not different between groups. Cell injury assessed by lactate dehydrogenase was 40% decreased in the APOSEC treated group 24 h post shock (p < 0.05). HTS-induced liver injury determined by plasma alanine aminotransferase was 1.6 and 1.5 fold higher in vehicle compared to APOSEC group at EOR and 24 h respectively. The 28-day mortality (25%) was prevented by APOSEC treatment (100% survival).

CONCLUSION: Here we show for the first time that APOSEC ameliorates the HTS-related apoptosis, inflammation, cell and liver injury, and long term outcome in rats.