Protective Effect Of Ulinastatin On The Renal Function During Cardiopulmonary Bypass At High Altitude In Dogs

Objective To investigate the effects on kidney during cardiopulmonary bypass at high altitude,to explore new predictors for early kidney damage during cardiopulmonary bypass at high altitude,and to research the effects and mechanism of ulinastatin on renal function during cardiopulmonary bypass at high altitude in dogs.Methods Twenty-four male healthy dogs at high altitude were randomized into three groups:control group with sham operation(group A,n=8);renal ischemic reperfusion injury (IRI) group with cardiopulmonary bypass(CPB)(group B,n=8) and ulinastatin treatment group with CPB(group C,n=8).Blood samples and urine samples were harvested at 0,2,6, 12,24 h after CPB,and the concentrations of blood urea nitrogen(BUN),serum creatinine (Cr) and endothelin-1(ET-1),urine N-acetyl-β-D-glucosaminidase(NAG) and urine glutamyl transpeptidase(γ-GTP) were measured.Left kidney was obtained for pathological examination 24h after CPB.Results Compared with group A,BUN and Cr levels were significantly higher at 12, 24 h after CPB in group B(P＜0.05,P＜0.01),NAG and ET-1 levels were significantly higher at 0,2,6,12,24 h after CPB in group C and in group B(P＜0.05,P＜0.01).γ-GTP levels were significantly higher at 0,2,6,12,24 h after CPB in group B(P＜0.01).γ-GTP levels were significantly higher at 0,12,24 h after CPB in group C(P＜0.05,P＜0.01). Compared with group B,BUN and Cr levels were significantly lower at 24 h after CPB in group C(P＜0.01),NAG and ET-1 levels were significantly lower at 0,2,6,12,24 h after CPB in group C(P＜0.01),γ-GTP levels were significantly lower at 6,12,24 h after CPB in group C(P＜0.05,P＜0.01).Histopathological examination:There was no evident morphological change in group A.Proximal convoluted tubule endepidermis vacuolar developed degeneration and cellular necrosis,cast and necrosis cells occurred in the broadened lumens of nephric tubule,and blood vessel around the nephric tubule obviously demonstrated dilatation and congestion in group B.Proximal convoluted tubule endepidermis revealed cellular swelling,granular degeneration in group C.Cast and blood vessel congestion was rarely found in this group. The Paller scores of group C and group B are higher than group A(P＜0.01).The group B's score is higher than group C's(P＜0.01).Conclusion1,Earlier period kidney damage is definite during CPB at high altitude.The mechanism maybe relate with renal ischemic reperfusion injury.2,ET-1 is possible an important initiating factor of renal ischemic reperfusion injury (IRI) after CPB at high altitude.3,Urease(NAG,γ-GTP) increased at the earlier phase of kidney damage in comparison with other parameters during CPB at high altitude.The degree of injury of renal function is positive correlation with the NAG level in urine.The factor of causing kidney damage and increasedγ-GTP have a positive correlation in urine.4,Ulinastatin can reduce the risk of renal dysfunction during CPB at high altitude. And decreased ET-1 level may be the mechanism of Ulinastatin to alleviate renal IRI.