The Clinical Study On The Protective Effects Of Adenosine Preconditioning On Pulmonary Ischemia-Reperfusion Injury

Objective To explore the protective effects and mechanism of adenosine preconditioning on pulmonary ischemia-reperfusion injury in patients undergoing open heart surgery.Methods Twenty patients with congenital heart defects who were undergoing open heart surgery were randomly divided into two groups :adenosine group (n=10)and control group(n=10).Adenosine(1.5mg/kg) was infused into the superior vena cava before beginning of cardiopulmonary bypass in adenosine group. the same volume of normal saline was infused instead of adenosine in control group. Aortic cross-clamping time, cardiopulmonary bypass time ,and spontaneous returned heartbeat situation were recorded. Plasma superoxide dismutase enzyme (SOD) activity, plasma maleic dialdehyde (MDA) content ,plasma nitric oxide (NO) content, and plasma tumor necrosis factor-α(TNF-α)content were measured in the former cardiopulmonary bypass (T1), immediately open aortic (T2), aortic open one hour (T3), aortic open three hours (T4), and aortic open 24 hours (T5). Blood oxygen (Pa02),the partial pressure of carbon dioxide (PaC02) ,and the oxygenation index values (Pa02 / Fi02) changes were recorded by arterial blood gas analysis in T2, T3, T4 , T5. Lung organizations were randomly selected in the 5 patients in the two groups before closing pleural, each group lung tissue structural changes were observed under light microscope, as well as lung tissue of nuclear factor-κB (NF-κB), heat shock protein 70 (HSP-70) gray value changes were examined by image analysis system. The lung ultrastructural changes were observed under Electron microscope.Results the difference of the two groups were not statistically significant in the aortic cross-clamping time, cardiopulmonary bypass time ,and spontaneous returned heartbeat situation(P>0.05). Compared with the control group, the plasma SOD activity of the adenosine group was increased, the plasma MDA of the adenosine group was reduced, the plasma NO release of the adenosine group was increased ,and the plasma TNF-αof the adenosine group was decreased,the difference was significant(P<0.01). There was no significant difference about the Pa02,PaC02,and Pa02/Fi02 changes between the two groups(P>0.05). Compared with the control group, the expression of HSP70 of the lung of the adenosine group was increased and lung tissue activation of NF-κB of the adenosine group was weakened, the difference was significant in the gray value(P<0.01).By the lung tissue pathology light microscopy observation,we found that there was much more polymorphonuclear leukocyte infiltration in the lung tissue of the control group than of the adenosine group. Lung tissue ultrastructure was observed under Electron microscope:in the control group , typeⅡalveolar epithelial cell surface microvilli was loss or reduction, lamellar body was reduced, mitochondria was vacuolization,vascular endothelial cell was swelling and the structure was destroyed, and alveolar interval was thickened;in the adenosine group,typeⅡalveolar epithelial cell surface microvilli was more and uniform distribution, there were a large number of lamellar bodys, mitochondria was less but not swelling, vascular endothelial cell was not swelling and no vacuolar structure, and the thick of alveolar interval was unchanged.Conclusions 1.Lung ischemia-reperfusion can cause significant damage to the lung tissue structure and function. Injury indicators: the plasma MDA content , the plasma TNF-αrelease,and the lung tissue NF-κB activity all were increased . Protection indicators: the plasma SOD activity, the plasma NO, and the lung tissue expression of HSP70 all were decreased. There was much more polymorphonuclear leukocyte infiltration in the lung tissue under light microscope. Lung tissue ultrastructure was observed under Electron microscope:typeⅡalveolar epithelial cell surface microvilli was loss or reduction, lamellar body was reduced, mitochondria was vacuolization, vascular endothelial cell was swelling and the structure was destroyed, and alveolar interval was thickened. 2. Adenosine preconditioning could enhance the activity of the plasma SOD ,reduce the content of the plasma MDA,improve the lung tissue antioxidant capacity, increase in the synthesis and release of endogenous NO, induce ischemia-reperfusion lung expression of HSP70, at the same time reduce activation of NF-κB, inhibit the release of TNF-α, inhibit the activation of polymorphonuclear leukocyte and the infiltration in the lung tissue, reduce ultrastructure injury of the ischemia-reperfusion lung, protect the typeⅡalveolar epithelial cell and the pulmonary vascular endothelial cell, reduce pulmonary capillary injury, thus the ischemia-reperfusion injury lung was protected.