The protective effect of Prostaglandin E1 combined with mild hypothermia on ischemic/reperfusion injury of pulmonary micro-vascular endothelium of ROSC rat

This study aims to investigate Prostaglandin E1 (PGE1) combined with mild hypothermia as a therapeutic intervention on ischemic/reperfusion (I/R) injury of pulmonary micro-vascular endothelium cells (PMEC) from return of spontaneous circulation (ROSC) rat with successful cardiopulmonary resuscitation (CPR). Ventricular fibrillation (VF) in 36 rats was induced by transoesophageal cardiac pacing with alternating current. They were divided into 4 groups after CPR: ROSC group (R), Hypothermia group (H), PGE1 group (P) and PGE1/Hypothermia group (PH). Another 3 rats without VF/CPR were set as Blank control group (B). Arterial blood gas was analyzed at 0.5 h, 4 h and 8 h post ROSC and 3 rats from each group were sacrificed at each time point. I/R injury of PMEC was evaluated through tissue morphology, hematoxylin and eosin (HE) staining, vascular endothelial (VE)-cadherin RNA expression with PCR, CD34/TUNEL and vascular endothelial growth factor receptor (VEGFR)/VE-cadherin double fluorescent immunohistochemistry (IHC) staining. PGE1, mild hypothermia and PGE1/hypothermia, all 3 interventions could significantly alleviate metabolic acidosis and hypoxemia (P<0.05) of ROSC rats to different levels at different time points. All 3 interventions could significantly improve pulmonary interstitial edema, hemorrhagic lesion, PMEC apoptosis, and alleviate VE-cadherin protein loss, while PGE1/hypothermia showed most dramatic effect. At 0.5 h, moderate compensation tendency of VE-cadherin RNA expression of the 3 interventions may indicate the less I/R injury of PMEC of ROSC rats (P<0.05). Both PGE1 and mild hypothermia could alleviate I/R injury of PMEC from ROSC rats respectively, while the PGE1/hypothermia combined intervention might have synergistic better effect than either single intervention.