Protective effects of morphine preconditioning on the lungs against ischemia-reperfusion injury in rabbits

Objective To investigate the protective effects of morphine preconditioning on the lungs against ischemia-reperfusion (I/R) injury and the possible mechanisms.Methods Twenty-four Japanese long-ear white rabbits weighting 2.5-3.0 kg were used in this study. The animals were anesthetized with intramuscular atropine 0.5 mg and intravenous 3 % pentobarbital 30 mg ·kg-1, tracheostomized and mechanically ventilated ( VT 10 ml·kg-1, RR 30 bpm, FiO2 100% , PEEP 1 cm H2O) . Right carotid artery was cannulated for BP monitoring and blood sampling. An elastic band was placed around the hilum of left lung via thoracotomy to perform lung ischemia. Body temperature was maintained at 36-38℃( rectal) . The animals were randomly allocated to one of 3 groups (n = 8 each) : (1) Sham group; (2) I/R group was subjected to 2 h in situ left hilar occlusion followed by 2 h reperfusion and (3) morphine preconditioning group received morphine 4 mg·kg-1 via pulmonary artery 30 min before I/R. Mean pulmonary artery pressure (MPAP) and peak inspiratory pressure (PIP) were monitored and recorded. Arterial blood samples were taken before occlusion of lung hilum (baseline) and at 5, 30, 60, 90 and 120 min of reperfusion for blood gas analysis, and determination of plasma endothelin-1 concentration. The animals were killed at the end of 120 min reperfusion. The lungs were removed for determination of lung water content (W/ D ratio), percentage of neutrophils in the broncho-alveolar lavage fluid ( BALF) and microscopic examination.Results MPAP and PIP were significantly lower while PaO2 was significantly higher at 30, 60, 90 and 120 min of reperfusion in morphine preconditioning group than in I/R group. Plasma endothelin-1 concentration was significantly lower at 60 and 120 min of reperfusion in morphine preconditioning group than in I/R group ( P 0.05).W/D ratio and percentage of neutrophils in BALF were significantly lower in morphine preconditioning group than in I/R group ( P 0.01).Conclusion Morphine preconditioning attenuates I/R injury to the lungs. Decrease in plasma endothelin-1 concentration after reperfusion and neutrophil function suppression may be involved in the mechanism.