Selective attenuation of acute lung ventilatory injury by methylene blue after liver ischemia-reperfusion: A drug response study in an isolated perfused double organ model

Background. Liver transplantation-related ischemia-reperfusion (IR) is asso ciated with the generation of stress oxidants that can spread damage remote ly. Methylene blue (MB) had been shown to reduce lung neutrophils sequestra tion after in vivo intestinal IR and to have a dose-dependent potential for abrogating oxidant-induced ex vivo aortal ring reperfusion injury after li ver IR. We now investigated MB's dose-dependent capabilities in preventing acute lung injury after the same liver IR. Methods. Wistar rat livers (eight replicates/group) were perfused (control) with modified Krebs-Henseleit solution or put globally in no flow (IR) con ditions for 2 hr. Separately prepared lungs were then paired with livers an d "reperfused" (15 min) together. The livers were then removed, and the lun gs were left to recirculate alone with the accumulated Krebs for 45 min. Th ree additional control and three IR groups were reperfused with Krebs conta ining 20, 40, or 60 mg/kg MB at concentrations of 42, 86, or 128 muM. Results. All IR livers had hepatocellular and biochemical abnormalities com pared with normal functions in the controls. Liver III was associated with a 50%-75% increase in lung ventilation and perfusion pressures, vascular re sistance and decreased compliance, and abnormal bronchoalveolar lavage (BAL ) volume and content. Adding 42 and 86 muM MB selectively maintained normal the vascular parameters, intra-experimental lung weight gain, BAL indices, and wet-to-dry ratios. MB128 muM but not 42 or 86 muM best prevented IR-in duced deterioration in lung ventilatory pressure and compliance. Conclusions. MB selectively affords maintenance of normal lung ventilatory versus vascular measures after liver ischemia-reperfusion. Its proposed dif ferential mechanism of action is discussed.