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 associated with the generation of stress oxidants that can spread damage remotely. Methylene blue (MB) had been shown to reduce lung neutrophils sequestration after in vivo intestinal IR and to have a dose-dependent potential for abrogating oxidant-induced ex vivo aortal ring reperfusion injury after liver 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) conditions for 2 hr. Separately prepared lungs were then paired with livers and "reperfused" (15 min) together. The livers were then removed, and the lungs were left to recirculate alone with the accumulated Krebs for 45 min. Three additional control and three IR groups were reperfused with Krebs containing 20, 40, or 60 mg/kg MB at concentrations of 42, 86, or 128 microM.


RESULTS
All IR livers had hepatocellular and biochemical abnormalities compared with normal functions in the controls. Liver IR was associated with a 50%-75% increase in lung ventilation and perfusion pressures, vascular resistance and decreased compliance, and abnormal bronchoalveolar lavage (BAL) volume and content. Adding 42 and 86 microM MB selectively maintained normal the vascular parameters, intra-experimental lung weight gain, BAL indices, and wet-to-dry ratios. MB128 microM but not 42 or 86 microM best prevented IR-induced 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 differential mechanism of action is discussed.
Weinbroum
A A
AA
Post Anesthesia Care Unit, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel.
Paret
G
G
Szold
O
O
Rudick
V
V
Krupitzky
L
L
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008102:Liver Circulation; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008171:Lung Diseases / Q000517:prevention & control*; D008297:Male; D008751:Methylene Blue / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012119:Respiration / Q000187:drug effects; D012129:Respiratory Function Tests; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D008751:Methylene Blue