The Protective Effects Of Activated Protein C On Cardiopulmonary Bypass Induced Lung Injury

THE CHANGES OF ACTIVATED PROTEIN C AND THE RELATIONSHIP BETWEEN ACTIVATED PROTEIN C AND ACUTE LUNG INJURY DURING CARDIO-PULMONARY BYPASSThe cardiac surgery has been safer with each passing day with development of cardio-pulmonary bypass(CPB)technology.However,postoperative complications,mainly acute lung injury(ALI],are still remaining in high morbidity.Beyond this,ALI can also develop to acute respiratory distress syndrome(ARDS)in some severe cases.Activated protein C(APC)is the activated form of vitamin K-depended plasma pepsinogen(protein C).APC is not only an anticoagulant factor which is considered to be the most important component of the protein C anticoagulation system,but also plays an important role in anti-inflammatory,anti-apoptosis,protection of endothelial cells et al.A number of experiments confirm that APC Is beneficial for acute lung injury.Objective:To investigate the role of APC played in ALI after CPB,by monitoring the dynamic changes of APC in venous blood.Materials and Methods:30 cases matching eligibility criteria were obtained from patients undergoing heart surgery with CPB in our hospital from May,2011 to March,2013.The blood samples were collected from central venous at ten time points as following:just after induction of anesthesia(T1),CPB starting[T2],10 minutes(T3],20 minutes(T4],30 minutes after CPB(T5),CPB stopping(T6),30 minutes(T7),4 hours(T8);8 hours after CPB(T9)and 30 minutes wean from ventilator(T10).The plasma was obtained by 4000rpm with low-temperature centrifuge and was stored in-80?.Plasma APC was detected by enzyme linked immunosorbent assay[ELISA)].The values of patients'PaO2,PaCO2,SO2,tidal volume and peak airway pressure were determined at the same time.The alveolar-arterial oxygen difference,oxygenation index,dynamic lung compliance were calculated to evaluate the changes in lung oxygenation and lung compliance.Lung injury at T8 were judged by Murray lung injury scoring system.The relationship between APC and indices of respiratory function were analyzed.Result:In our research,APC increased rapidly at the beginning of CPB and reached a peak at 10 minutes after CPB;and then declined slowly and formed a plateau phase.PA-aDO2 of T6~T10 were obviously higher than those of T1(P<0.01),OI of T6~T10 were obviously lower than those of T1[P<0.01],and RI of T6?T10 were obviously higher than those of T1(P<0.05).According to Pearson rank correlation analysis,no significant association was found between concentrations of plasma APC at T8 and degrees of lung injury at the same time judged by Murray scoring system(P=0.587,>0.05),and it was also the same result between concentrations of plasma APC and PA-aDO2,OI,RI,The difference between peak concentration of plasma APC and the concentration of APC before CPB starting(T1)was negatively correlated with degrees of lung injury judged by Murray scoring system(T8;r=-0.851,P<0.01),PA-aDO2[P<0.01[T7?9],P<0.05(T10)]3]and RI[P<0.01[T7?9],P<0.05[T10]],and it was positively correlated with OI[P<0.01[T7?9),P<0.05[T10)]at the time of T7,T8,T9,T10.Conclusions:The level of plasma APC in veinal blood significantly increased after cardiopulmonary bypass.No close correlation was found between patients' concentrations of plasma APC and ALI indicators,but the increased extent of APC caused by CPB is closely related to acute lung injury indicators after operation.THE PROTECTIVE EFFECTS OFACTIVATED PROTEIN C ON CARDIO-PULMONARY BYPASS INDUCED LUNG INJURYObjective:Cardiopulmonary bypass is known to induce systemic inflammatory responses that injure multiple organs,especially the lungs.Activated protein C has been demonstrated to play an important role in the regulation of inflammation.We investigated the anti-inflammatory effects of activated protein C on a rat model of cardiopulmonary bypass.Methods:Forty eight SD rats were randomized divided into four groups(12 for each group],including Control(C)group,0.5U/kg thrombin(T)group,0.1mg/kg activated protein(A)group and 0.1mg/kg APC+0.5U/kg thrombin(A+T)group.Rats underwent cardiopulmonary bypass for 60 minutes followed by another 60 minutes observation.The blood was collected for detecting CD11b/CD18,IL-8,neutrophil elastase(NE)at different time points of 0,60 and 120 minutes after the drugs injection.At the end of the experiment,the left lower lobe was kept for W/D lung weight ratio measurement,the right lung was lavaged and bronchoavleolar lavage fluid(BALF)was collected to count the number of total neutrophil and protein used to evaluate the pulmonary microvascular permeability index(PMPI).The left upper lung lobe in each group was sectioned and stained with hematoxylin-eosin.Tissue tumor necrosis factor alpha(TNF-?)concentration in the left superior lung were detected.Results:Compared with the control group,the TNFa,W/D,CD11b/CD18,IL-8,NE,PMPI were significantly lower in A group and A+T group.On the contrast,these indices of T group were significantly higher.HE staining of the lung sections of the control and T groups showed interstitial edema,alveolar hemorrhage,and severe neutrophil accumulation.Inflammatory in the A group and A+T group lung was minimized(P<0.05).Conclusion:Application of activated protein C(0.1mg/kg)before cardio-pulmonary bypass attenuates acute lung injury induced by cardiopulmonary bypass,at least in part through that APC reversed the elevation of the pulmonary microvascular permeability induced by thrombin.