Methylene Blue Attenuates Pancreas Ischemia–Reperfusion (IR)-Induced Lung Injury: A Dose Response Study in a Rat Model

• Published in: Journal of gastrointestinal surgery 2009-09, Vol.13 (9), p.1683-1691
• Main Author: Weinbroum, Avi A.
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - prevention & control; Allopurinol - pharmacology; Amylases - metabolism; Analysis of Variance; Animals; Antioxidants - pharmacology; Bronchoalveolar Lavage Fluid - chemistry; Disease Models, Animal; Dose-Response Relationship, Drug; Gastroenterology; Glutathione - metabolism; Ischemia; Lipase - metabolism; Lungs; Male; Medicine; Medicine & Public Health; Methylene Blue - pharmacology; Original Article; Pancreas; Pancreas - drug effects; Pancreas - pathology; Probability; Pulmonary Circulation - drug effects; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Rodents; Surgery; Xanthine Oxidase - metabolism
• ISSN: 1091-255X; 1873-4626
• DOI: 10.1007/s11605-009-0945-0

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. Materials and 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 ∼60% increase in ventilatory plateau pressure and final P o 2 /Fi o 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 μM MB were minimally damaged, whereas perfusion solutions containing 42 or 128 μM MB were ineffective in preventing lung injury. Conclusions Ex vivo pancreas IR-induced ALI is preventable by MB, although at a narrow dose range.