Study Of The Effects Of Aprotinin On Pulmonary Ischemia-reperfusion Injury

Objective: To investigate the positive effects and mechanisms of aprotinin on lung protection and the prevention of ischemia / reperfusion injury by using an In situ normothermic ischemic lung model of rabbit.Methods: Eighteen New Zealand white rabbits were randomly divided into 3 groups: control group, LPD group and aprotinin group, each of them are six. Lung protection solution was supplied to the left pulmonary artery via a catheter after the left pulmonary artery were clamped. After applying the solution, ischemia was carried out for 120 min. At the end of this period, reperfusion was carried out for 90 min. In the control group, pulmonary perfusion solution was not employed, the other procedures were the same as the other two groups. Whereas in the LPD group low potassium dextran ( LPD) was employed, and in the aprotinin group aprotinin containing LPD solution(LPD±aprotinin) were perfused. Blood gas analysis, and TNF—a were measured before ischemia and at the 15th , 60th and 90th minutes of reperfusion. The lung tissue samples were obtained at 90th minutes of reperfusion. The pulmonary water content(D/W), tissue myeloperoxidase (MPO) activity, content of tissue malondialdehyde (MDA) were measured, and microscopic examination of lungs was conducted .Results: The aprotinin group showed significantly higher levels of PaO₂ at the 15th, 60th and 90th minutes of reperfusion(276.33 ± 26. 93, 264.83 ± 29. 92 and 307.83±19. 64 mmHg)in comparison to control group (122.50±20. 71, 64.50± 5. 65 and 100.00±3. 50mmHg) (P < 0.01) and also had significantly higher levels of PaO₂ at the 15th and 90th (except the 60th ) minutes of reperfusion when compared to LPD group (225.67±35. 386 and 240.67 ± 41. 87mmHg) (P < 0.01). Aprotinin group not only showed significantly lower levels of TNF-a at the 15th when compared to control group( 72.47±3. 69 pg/ml) (P < 0.05), but also had thesignificantly lower levels of TNF-a at the 60th,90th minute of reperfusion (71.12± 8. 77 and 69.87+7. 47 15 pg/ml) in comparison to the LPD (86.90+3. 45 and 90.17 ±2. 37 pg/ml) and control (98.45 + 2. 81 and 103.67+4. 40 pg/ml) groups (P < 0.01). The MPO activity was significantly lower in the aprotinin group (6.73 ±0. 98) compared to the LPD (10.76+1. 05) and control(14.08+1. 70) groups. MDA levels were significantly lower in the aprotinin group (3.83 + 1. 96 nmol nmol/mg) when compared to the LPD(7.21 +1. 05 nmol/mg) and control (11.96+1. 70nmol nmol/mg) groups (P < 0.01). The ratio of D/W were significantly higher in the aprotinin group(0.19 + 0. 01)) compared to the LPD(0.16±0. 01) and control(0.13+0.01) groups (P < 0.01). In addition, The microscopic examination also showed that there were less severe infiltration and edema formation in the alveolar space in aprotinin group when compared to control and LPD groups.Conclusions: It was observed that the addition of aprotinin to LPD solution as apulmonary flush solution in an in situ normothermic ischemic lung model prevents ischemia / reperfusion injury and further increased the lung protection of LPD solution.