Protective Effects Of Hypothermic Pulmonary Solution On Lung Function In The Correction Operation Of Tetralogy Of Tallot

Background:postoperative lung dysfunction remains as a most important complication after cardiopulmonary bypass,particularly for children suffered from Tetralogy of Fallot.There are no specific treatment in the clinical practice at present. Recently,it is found that pulmonary perfusion with hypothermic protective solution including aprotinin.This study was to evaluate the protective effect of pulmonary perfusion with hypothermic protective solution including ulinastatin on lung function after cardiopulmonary bypass.Subjects:Thirty children who had CHD of right to left shunts with tetralogy of fallot(TOF)were enrolled and had been performed the radical operation under CPB from Sep 2006 to Apr 2007 in the department of cardiovascular surgery,children's hospital of Zhejiang University in this study.All clinical materials were achieved via the clinical history,physical examinations,chest roentgenography, electrocardiography and ultrasound-doppler examination.There were sixteen four boys and fourteen girls in thirty children,whose median age was 16.25±7.15 months old(ranged from 9months to 39 months),and median weight was 10.36±3.39.There were 20 children with PFO,6 children with ASD,2 children with PDA and the last with LSVC.Thirty children were allocated to the perfused group(n=15)and the control group(n=15)at random before operation.The two groups didn't differ significantly with regards to demographic or surgical data.The patients with leukocyte＞12000/μl,temperature＞38℃or CRP＞8mg/L before the operation were excluded in this study.Methods:After inhalation and intravenous combined general anesthesia,all children were performed the radical operation under moderate hypothermia CPB.Children in the control group only received 4℃cardioplegia after aortic clamping,whereas children in the perfused group received 4℃cardioplegia and 4℃pulmonary protective solution after aortic clamping.The solution were sucked out of left atrium by a drain.The heart perfusions were repeated when cross-clamp time was more than 30minutes.The ultrafiltration were routinely used in all children.The protective solution involved ulinastatin(10,000KIU/kg),anisodamine(1mg/kg), methylprednisolone(30 mg/kg),L-arginine(0.2 g/kg),5%sodium hydrogen carbonate(1 ml/kg)and dextran 40(60ml/kg).A series of arterial blood samples were analyzed with a blood gas analyzer at four different time points:pre-operation,0 hours, 3 hours,6 hours after the sternum closed.Pulmonary function indexes were collected from the respirator at the same time.Blood samples were collected for measuring the mean fluoresence intensity(MFI)of PMN CD11b and the concentration of tumor necrosis factor-αat five different time points:pre-operation,0 hours,3 hours,6 hours and 24 hours after the sternum closed.The MFI of PMN and CD11b were detected by flow cytometre.The tumor necrosis factor-αlevels in plasma were measured in duplicate by using a commercial radioimmunoassay kit..Lung biopsies were obtained after weaning from CPB.Some pieces of the tissue were fixed in 10% buffered Formalin for light microscopy,other were immersed in universal fixative (2.5%glutaryl-aldehyde)immediately after biopsy for electron microscopy.Statitical analysis:The data are presented as mean values±standard deviation.Differences between groups were tested for significance by the Student's t test for unpaired samples or repeated measures of analysis of variance.The data were processed using the Statistica SPSS 14.0 software package for Windows(SPSS Inc,IL,Chicago)and differences were considered statistically significant at a probability level of less than 0.05.Results:1.There was no mortality in this study.Hospital stays had no statistical difference between the groups.The mean time of mechanical ventilation was shorter in the perfused group compared with the control group(27.73 hours versus 41.91 hours; t=2.346,P＜0.05).2.Assessment of Lung Function:Alveolar-arterial O₂ gradient(A-aDO₂,mmHg) increased in both groups after sternum closed.The A-aDO₂ reached the vertex when the sternum is closed,then came back gradually.A-aDO2 was lower in the perfused group than in the control group and the differences were significant at 3 hours and 6 hours after the sternum closed(F=3.87,P＜0.05;F=8.29,P＜0.01). Dynamic compliance(Cdyn,ml/cmH₂O/kg)descended in both groups after sternum closed.The nadir is the point of the sternum closed.The values came back since that time,but remained low compared to pre-bypass.Cdyn was higher in the perfused group than in the control group and the differences were significant at 3 and 6 hours after sternum closed.(F=2.21,P＜0.05;F=3.28, P＜0.05).Cdyn,ml/cmH₂O/kg)(A-aDO₂,mmHg)3.Analysis of Blood:The MFI of PMN CD11b increased in both groups after the sternum closed.The increasing extents of MFI were lower in the purfused group than in the control group at 3 and 6 hours after the sternum closed(F=6.48, P＜0.01;F=4.56,P＜0.05).The tumor necrosis factor-αlevels increased in both groups after sternum closed.The incresing degree of tumor necrosis factor-α levels was lower in the protective group and were significantly different at 0 and 3 hours after the sternum closed F=2.66,P＜0.05;F=7.85,P＜0.01)).4.Pathologic analysis of lung tissue:Light microscope studies disclosed that there are a lot of inflammatory cells effusion and accumulation in the control group in contrast of the perfused group.Electron microscopic studies revealed gas-blood barrier broadening,tomentum fallen off lung and epithelium mitochondria swelling and vacuolation in the control group,whereas there were no significant changes in the perfused group.Conclusions:1.Lung perfusion with hypothermic solution during CPB alleviate the inflammatory reactions,consequently allaying CPB-induced lung injury.2.lung perfusion with hypothermic solution during CPB relieved the acute lung injury from children with TOF at a certain extent,shorten the time of ventilation and improved the early lung function recovery after operation.