Mannitol prevents acute lung injury after pancreas ischemia-reperfusion: a dose-response, ex vivo study.
Oxidants and their generator, xanthine oxidase (XO), play a major role in the damaging of the structural and functional integrity of the lung. Such damage has been recently demonstrated in the presence of pancreas ischemia-reperfusion (IR). We investigated whether mannitol, a clinically used agent and antioxidant, prevented lung damage after pancreas IR. Rats (n = 48) were anesthetized, after which each pancreas was isolated and perfused (controls), or made ischemic (IR) for 40 min, or made ischemic and treated upon reperfusion with four different doses of mannitol administered in the perfusate (8 replicates/group). Ischemia was followed by in-series 15-min pancreas plus normal isolated lung reperfusion. Isolated lungs were subsequently perfused for 45 min with the 15-min accumulated effluents. Pancreas injury occurred in all IR organs as demonstrated by abnormal reperfusion pressure, the wet-to-dry ratio, amylase and lipase leakage into the circulation, and XO activity and reduced glutathione (GSH) pool in the tissues. Pulmonary plateau pressure increased by 80%, and final PO(2)/FiO(2) decreased by 28% in the IR-untreated paired lungs. Bronchoalveolar lavage volume increased by 50% and 2- to 8-fold increase in their contained XO and GSH were recorded as well. The above indices of injury in lungs perfused with 0.77 mM mannitol were the least detected, compared with negligible efficacy of other (0.55 < 0.22 < 1.1 mM) dosages. Amylase and lipase did not contribute to lung injury. Ex vivo acute pancreatitis induces acute lung injury via oxidants/antioxidants imbalance, which is preventable by mannitol.
Weinbroum
Avi A
AA
The 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 / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000681:Amylases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010182:Pancreatic Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D008353:Mannitol; D014969:Xanthine Oxidase; D008049:Lipase; D000681:Amylases; D005978:Glutathione