The filtration coefficient (Kf) in Starling's equation for fluid exchange was estimated in isolated reperfused canine lobes to evaluate the effect of ischemia-reperfusion injury on alveolar-capillary permeability quantitatively and to determine the inhibitory effects of a high dose of methylprednisolone (MPS) or dimethylthiourea (DMTU), a potent hydroxyl radical scavenger, on this injury. We reperfused isolated canine left lower lobes (LLLs) with blood at a constant flow after 3 hr of warm (38°C) or cold (4°C) ischemia and measured Kf after 1 hr of reperfusion. The mean value of Kf (±1 SD) in the cold ischemic lobes (COLD, n = 7), 0.13 ± 0.04 g·min-1·cmH2O-1·100 g-1, was not different from that in the control nonischemic lobes (CONT, n = 6), 0.10 ± 0.04 g·min-1·cmH2O-1·100 g-1. In contrast, the mean value of the Kf in the warm ischemic lobes (WARM, n = 7), 0.38 ± 0.17 g·min-1·cmH2O-1·100 g-1, was significantly (P < 0.001) higher than in CONT. MPS (30 mg/Kg) or DMTU (0.75 g/kg) administered before isolation of LLL and before reperfusion reduced the increase in Kf in warm ischemic lobes to 0.19 ± 0.09 and 0.19 ± 0.05 g·min-1·cmH2O-1·100 g-1, respectively (P < 0.005 WARM vs MPS, and P < 0.01 WARM vs DMTU). MPS and DMTU also attenuated the impairment of gas exchange. We conclude that (1) reperfusion after 3 hr of warm ischemia increases Kf but after cold ischemia does not, and (2) MPS and DMTU prevent the increase in Kf. Our data suggest that the ischemic-reperfusion lung injury may be due in part to the hydroxyl radical and some pharmacological agents can prevent the injury by attenuating increase in pulmonary microvascular permeability.
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