Effects of Modified Ultrafiltration on Aquaporin 1 in Cardiopulmonary Bypass
|School||Zunyi Medical College,|
|Keywords||modified ultrafiltration cardiopulmonary bypass Aquaporin 1 lung edema|
Object: To explore the mechanisms of acute lung injury induced by cardiopulmonary bypass, through investigating the change of expression of aquaporin 1(AQP1) in lung tissue after modified ultrafiltration being used in cardiopulmonary bypass (CPB) for reducing lung injury.Methods:18 adult hybrid healthy dogs (15-20kg), were randomly divided into three groups (n=6):control group (group A), CPB group (group B) and modified ultra-filtration group (group C). All the dogs were anesthesitized with 2.5% sodium pentobarbital (25mg/kg). The trachea was intubated with a cuffed endotracheal tube. A femoral artery catheter was placed for mean arterial pressure (MAP) monitoring and blood sampling. A femoral vein catheter was placed for central venous pressure (CVP) monitoring and transfusion. The CPB mode was established in group B and C simulating clinical thoracotomy. The thoracotomy was performed in group A but without CPB. Modified ultra-filtration was executed in group C 15 min after CPB. Samples of arterial blood and lung tissue were collected at T1 (before mechanical ventilation), T2 (end of CPB), and T3 (60min after CPB). Samples of arterial blood were used to calculate respiration index (RI) and oxygenation index (OI). Samples of lung tissue were collected to observe changes of pathology with light microscope, to measure the level of mRNA of AQP1 with real-time PCR and protein expression of the AQP1 with western-blot.Results:(1) In group A, the structure of lung tissue in optical microscope was in order, without filler in lung alveolar. In group B, The structure of lung tissue in optical microscope was disorder, with massive inflammatory cell infiltrating, alveolus capillary dilating and congesting, alveolar wall congesting obviously, alveolar septum widening, massive erythrocyte appearing in alveolar space and focal atelectasis. No lung edema was found in group C, except seldom inflammatory cell infiltrating.(2) There was no significant difference between RI and 01 in all groups at T1 (P>0.05). RI in group B and C at T2 and T3 were obviously higher than at T1, but OI at T2 and T3 was lower than T1 (P<0.05). Comparing with A gourp, RI in group B and C were significantly higher, whereas OI were lower at the same time points (P<0.05). RI was decreased in ultra-filtration group than the CPB (P<0.05). OI of each group was not changed at T1 (P> 0.05), but which in CPB group was significantly decreased compared with the control group at T3, T4(P<0.01). RI was increased in ultra-filtration group compared wtih the CPB group (P<0.05).(3) There was no difference in the expression of AQP1 mRNA between all groups at T1 (P> 0.05). Comparing with T1, the expression of AQP1 mRNA in group A at each time point was not changed (P>0.05). The expression of group B and C at T2 and T3 were significantly lower than T1 (P<0.05). Comparin with group A, the expressions in group B and C at the same tine point were significantly lower (P<0.05). The protein levels of AQP1 in group B lung tissue were statistically lower than the group A (P<0.05), but which in group C was higher than group B (P<0.05).Conclusion:(1) Cardiopulmonary bypass can induce congestion, infiltration of inflammatory cell, decrease the expression AQP1 in lungs of dogs even acute lung edema to result in damage of lungs.(2) Modified ultrafiltration in cardiopulmonary bypass can increase oxygenation index, decrease respiratory index and relieve lung injure. Up-regulation of AQP1 may be involved in the mechanism of the lung protection of modified ultrafiltration.