Lung Injury After Cardiopulmonary Bypass In Juvenile Rats Model Is Protected By Adenosine A2a Receptor Agonist CGS21680

Objective In this study, To explore adenosine A2a receptor agonist CGS21680wouldattenuate lung injury after cardiopulmonary bypass in juvenile rats throughestablishment of the juvenile rats cardiopulmonary bypass model.Methods Thirty-six Juvenile Sprague-Dawley rats were randomly divided into threegroups：sham group（n=12），CPB group（n=12） and adenosine group（n=12）. Theright side femoral artery is used for arterial blood perfusion. The venous cannula in theright internal jugular vein was allowed for complete drainage of the right atrium,superior vena cava, as well as the inferior vena. The CPB circuit was primed with blood.Extracorporeal circulation was slowly initiated to a final flow rate of80–100(ml/kg)/min. CPB group and adenosine group underwent60-minute cardiopulmonarybypass. CGS-21680（120ug/kg）was added to the priming solution in the adenosinegroup before CPB. The control group underwent cannulation and heparinization only.Arterial blood pressure and blood gas were monitored in preoperative, intraoperativeand postoperative. Plasma was collected in each group at baseline，CPB30min，CPB60min and after CPB60min for IL-1β and GSH-PX analysis.The chest was opened aftersurgery，the lung was then isolated and stored at-80°until TNF-α and MPO analysiswere performed. The remaining was fixed by4%formaldehyde solution for lightmicroscopy observation.Results①Surgery was successfully performed in all the thirty-six juvenileSprague-Dawley rats.3rats died in respiratory and heart failure after CPB in CPB group, the adenosine group were died2after CPB. According to the preoperative,intraoperative and postoperative invasive blood pressure monitoring and blood gasanalysis results,blood pressure was stable and oxygenation was well, basically meet therequirement of CPB in children.②Lung tissue TNF-α and MPO were significantlyincreased in the CPB group compared to the Sham group. Histopathology revealed therewas more lung injury in the CPB group compared to the Sham group. The CPB grouphad significantly decreased in plasma GSH-PX，and increased in plasma IL-1βcompared to the Sham group.③Lung tissue TNF-α and MPO were significantlydecreased in the adenosine group compared to the CPB group. Histopathology revealedthere was less lung injury in the adenosine group compared to the CPB group. Theadenosine group had significantly increased in plasma GSH-PX，and decreased inplasma IL-1β compared to the CPB group.Conclusion①Establishment of cardiopulmonary bypass model in the juvenile ratsthrough this method is stable and practical. Using peripheral cannulation, venousdrainage unobstructed, a reasonable choice of a venous drainage needle and primed withblood are the key to successful establishment.②The CPB had increased plasma IL-1βand lung tissue TNF-α，MPO，had decreased plasma GSH-PX，result in lung injury aftercardiopulmonary bypass.③The addition of CGS21680to the priming solution prior tothe initiation of CPB significantly protects lung from CPB and reduces the amount oflung injury.