Concomitant administration of mannitol and N-acetylcysteine for the prevention of lung reperfusion injury.
BACKGROUND
Mannitol (MN) and N- acetylcysteine (NAC) are partially successful in preventing lung reperfusion injury after liver ischemia reperfusion (IR). Their concomitant administration might enhance the individual effects of each.


METHODS
Rat isolated livers were perfused with Krebs-Henseleit solution (controls) or made globally ischemic (IR) for 2 hours. Separately isolated lungs were paired with livers and each pair was reperfused in-series for 15 minutes. During reperfusion, eight groups were treated with Krebs containing two low and two high doses of MN and/or NAC; one group received no treatment.


RESULTS
The tested lung parameters were unchanged in all control groups. Pulmonary perfusion or ventilatory pressures, weight gain and bronchoalveolar lavage volume increased by 30 to 70% of baseline in the nontreated IR-paired lungs and in the only IR-MN 0.44- and the IR-NAC 0.25 mmol (weight/body weight) treated lungs but remained preserved by the two higher monotherapies (MN 0.55 mmol and NAC 0.37 mmol) and by the four bitherapies. The reduced glutathione content in all lung tissue subgroups treated by the bitherapies was higher by 63 to 124% of the corresponding monotherapy values. Xanthine oxidase activity in the bitherapies-treated IR-lungs decreased 1.5 to twofold compared with the corresponding monotherapies.


CONCLUSIONS
Co-administration of MN and NAC augments the amount of lung protection afforded by each drug individually and enhances their antioxidant potentials.
Weinbroum
Avi A
AA
Post-Anesthesia Care Unit and Animal Research Laboratory, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Israel. draviw@tasmc.health.gov.il
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000494:pharmacology; D007511:Ischemia / Q000628:therapy*; D008099:Liver / Q000098:blood supply*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D004338:Drug Combinations; D016166:Free Radical Scavengers; D008353:Mannitol; D000111:Acetylcysteine