Focusing lung transplant: physiological and antioxidant responses and effect of allopurinol to ischemia-reperfusion oxidative stress under different inspired oxygen concentrations

Background: To evaluate the effect of alopurinol after lung ischemia-reperfusion (IR) injury under ventilation with different inspired oxygen concentrations (0.21 and 1.00 pO2) on physiological responses and tissue damage and antioxidants present in lung parenchyma.Methods: Sixty Wistar rats were randomly allocated to six groups.Group 1 or control group (G1), Groups 2 and 3 (G2 and G3) animals ventilated during ischemiareperfusion with 0.21 and 1.00 pO2, respectively.The three other groups (G1A, 2A and 3A) were pre-treated with 100 mg/kg allopurinol and submitted to similar procedures as groups 1, 2 and 3, respectively.The model used was normothermic ischemia-reperfusion in situ.Duration of ischemia and reperfusion was 30 and 10 minutes, respectively.Outcome measures included mean systemic arterial pressure (SAP), partial pressure of oxygen/inspired fraction of oxygen (PaO2/FiO2) ratio, lung wet/dry weight ratio, and markers of oxidative stress in lung parenchyma, such as levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), as well as activity of catalase (CAT) and glutathione peroxidase (GPx).Results: After IR at normoxia (0.21pO2) ventilation were detected a decreased SAP, higher PaO2/FiO2 ratio, lower pulmonary edema, and also attenuated lung damage measured as markers of oxidative stress (lower TBARS and higher GSH levels) compared to hyperbaric ventilation (1.00 pO2).Animals pretreated with allopurinol revealed decreased values in SAP (G2xG2A and G3xG3A), in the ratio PaO2/FiO2 (G3xG3A), in TBARS levels and GPx and CAT activity (G3xG3A), while showing a significant increase in wet/dry weight ratio (G3xG3A).Conclusions: Ventilation at normoxia compared to hyperoxia showed better physiological responses (decreased SAP, higher PaO2/FiO2 ratio, lower pulmonary edema) as well as considering the oxidative stress markers in lung parenchyma (lower TBARS and higher GSH levels) after IR.Pretreatment with allopurinol was able to improve all these parameters, including the responses of antioxidant enzymes.Therefore, ventilation under normoxia and use of allopurinol should be recommended for lung transplantation and organ preservation to attenuate IR injury in lung.