Mannitol dose-dependently attenuates lung reperfusion injury following liver ischemia reperfusion: a dose-response study in an isolated perfused double-organ model.
We had previously studied different modes of prevention of liver ischemia-reperfusion (IR)-induced remote organ reperfusion injury, a challenge that remains partly unmet. We have now studied the capability of mannitol at different doses in abrogating liver IR-induced lung reperfusion injury in an isolated double-organ model. Rat livers ( n = 8/group) were perfused with Krebs-Henseleit solution (control) or made globally ischemic (IR) for 2 h, after which they were paired with normal lungs and "reperfused" together for 15 min. The lungs were then perfused alone with the accumulated Krebs for an additional 45 min. Another 4 control and 4 IR pairs were reperfused with Krebs containing mannitol at.22 mmol,.55 mmol,.77 mmol, or 1.1 mmol. Mannitol.22 mmol and 1.1 mmol failed to attenuate IR-lung injury as indicated by 50-95% increases in inspiratory and perfusion pressures and compliance reduction, a 70% increase in weight gain, and a 2-50-fold increase in bronchoalveolar lavage volume and content. Mannitol.55 mmol prevented all these abnormalities, and.77 mmol attenuated only changes in ventilatory parameters. The latter two treatments were also associated with a 50% reduction in xanthine oxidase activity and a 35-45% increase in the reduced glutathione tissue content compared with the nontreated IR-paired lungs. It is concluded that mannitol in a narrow therapeutic dose range can reduce oxidalive stress-induced lung damage that is related to liver IR.
Weinbroum
A A
AA
The Post-Anesthesia Care Unit and 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
Shapira
I
I
Ben-Abraham
R
R
Szold
A
A
Abraham
R B
RB
D000818:Animals; D004234:Diuretics, Osmotic / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000098:blood supply*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage* / Q000627:therapeutic use; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D004234:Diuretics, Osmotic; D008353:Mannitol