Methylene blue attenuates pancreas ischemia-reperfusion (IR)-induced lung injury: a dose response study in a rat model.
BACKGROUND
Oxidants (and their generator, xanthine oxidase [XO]) play a role in inducing acute lung injury (ALI) expressed both structurally and functionally. Such damage has recently been demonstrated in the presence of pancreas ischemia-reperfusion (IR). We now investigated whether methylene blue (MB), a clinically used coloring agent and antioxidant in itself, protected the lung exposed to pancreas IR.


METHODS
Isolated pancreata (eight replicates/group) were (1) continuously perfused (controls), (2) made ischemic (IR-0) for 40 min and reperfused without treatment, (3) organs procured from allopurinol-treated rats made ischemic and reperfused with allopurinol, and (4) made ischemic and treated upon reperfusion with three different doses of MB contained in the perfusate. All perfusate solutions were directed into the isolated lungs' circulation whereby they were perfused for 60 min.


RESULTS
Pancreas injury was documented in all IR organs by abnormally high reperfusion pressure, wet-to-dry ratio, amylase and lipase concentrations, and abnormal XO activity and reduced glutathione in the circulation. Lungs paired with IR-0 pancreata developed approximately 60% increase in ventilatory plateau pressure and final PO(2)/FiO(2) decrease by 35%. Their weight during reperfusion and bronchoalveolar lavage (BAL) volume and contents increased 1.5-2.5 times the normal values; XO and reduced glutathione values were abnormal both in the BAL and in the lung tissues. Lungs exposed to IR effluents containing allopurinol or 68 microM MB were minimally damaged, whereas perfusion solutions containing 42 or 128 microM MB were ineffective in preventing lung injury.


CONCLUSIONS
Ex vivo pancreas IR-induced ALI is preventable by MB, although at a narrow dose range.
Weinbroum
Avi A
AA
Animal Research Laboratory, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. draviw@tasmc.health.gov.il
D055371:Acute Lung Injury / Q000188:drug therapy / Q000517:prevention & control*; D000493:Allopurinol / Q000494:pharmacology*; D000681:Amylases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D011336:Probability; D011652:Pulmonary Circulation / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D000493:Allopurinol; D014969:Xanthine Oxidase; D008049:Lipase; D000681:Amylases; D005978:Glutathione; D008751:Methylene Blue