Suppressive Effect Of Phosphodiesterase Type 4 Rolipram Inhibition On The Inflammatory Response Induced By Cardiopulmonary Bypass In A Rat Model.

Background and ObjectiveThe appropriate inflammatory response caused by surgical trauma is a protective measure in the early period of cardiopulmonary bypass (CPB).It can play against infection and repair injury .However, with the prolonging of operation time, the "twice-hit" caused by intestinal bacterial translocation and ischemia-reperfusion injury makes inflammatory response uncontrolled , The release of inflammatory mediators , enzymes, oxygen radicals and endotoxin affect the function of organs , even lead to or accelerate single or multiple organ dysfunction syndrome. More and more study indicated that the inflammatory mediators are the main factors of inflammatory response of CPB. As the release of the cytokine has the characteristic of cascade and network, therefore, it will be too difficult to achieve the expectations by blocking single cytokine. It has been demonstrated that NF-κB have complex effects in a variety of cytokine gene transcription. And as a second messenger of neurotransmitters, hormones and other substances, cAMP have double regulation in the adenylate of cyclase synthesis and the decomposition of phosphodiesterase (PDE),PDE-4 is the cAMP-specific and lies in various inflammatory cells. At present, the main study of rolipram is concentrated on Alzheimer, depression and chronic obstructive pulmonary disease (chronic obstructive pulmonary Disease COPD). There are no relevant reports of rolipram in the cardiovascular surgical research at home and abroad. We will investigate the effect of selective PDE4 inhibitor (rolipram) on CPB-induced systemic inflammatory response in the rat model.MethodsRats were divided into two groups: control group(C) and rolipram interventional group(R). In both groups, arterial cannulation is retrograded in left carotid artery and drainage tube is punctured via right jugular vein to right atrium, animals underwent CPB at a flow rate of 45-55ml/kg per min for 30. Rats in interventional group were given intraperitoneal rolipram 30min before operation and then continuous intravenous infusion (40microg/kg/min) ever since the establishment of CPB to the end. TNF-a was measured with enzyme immunoassay; P-selectin was measured with immunohistochemisty; LPS was determined by limulus reagent kinetic turbidinetricassay . Lung tissues were dyed with Hematoxylin Eosin(HE) staining and observed with light microscope . The pulmonary pathology microscopic changes and lung injury were assessed according to its performance.ResultsRolipram reduced the secretion of TNF-a (P<0.05) and decreased the P-selectin expression of vascular endothelial cell (P<0.05); Rolipram inhibited the increase of LPS too (P<0.05).ConclusionRolipram inhibited secretion of TNF-a, LPS and expression of P-selectin in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be feasible therapeutic strategy to prevent exaggerated inflammatory response and organ injury in patients undergoing cardiopulmonary bypass.