Liver glutathione level influences myocardial reperfusion injury following liver ischemia-reperfusion.
BACKGROUND
N-acetyl-L-cysteine (NAC) both replenishes reduced glutathione (GSH) and mitigates reperfusion injury. We hypothesized that liver content of GSH could affect remote myocardial reperfusion injury following liver ischemia-reperfusion.


METHODS
Following stabilization (30 min), isolated rat livers (6/group) were perfused with Krebs-Henseleit solution (two control groups) or made globally ischemic (two ischemia groups) for 120 min. Paired livers + paced hearts (Langendorff preparation) were then reperfused for 15 min after which the hearts were recirculated alone for 50 min. NAC was added to Krebs (2 mM) that perfused livers during stabilization and reperfusion phases in one control and one ischemia group.


RESULTS
GSH levels in the two control liver groups were identical (30.1 +/- 5.7 [SD] nmol/mg protein), and similar to that of the ischemia + NAC livers (28.6 +/- 2.8) but 2-fold that of the ischemia + 0 livers (15.8 +/- 2.4 nmol/mg protein, p<0.05). While hearts paired with control livers maintained unchanged their myocardial velocity of contraction, the contraction in the ischemia + NAC-paired hearts reduced, but was better than in the ischemia + 0-paired hearts (71 +/- 8% vs. 41 +/- 6% off baseline, p<0.05). Coronary flow also decreased dissimilarly in the two ischemia-associated groups of heart: 72 +/- 9% (ischemia + NAC) vs. 46 +/- 7% (ischemia + 0, p<0.05). Xanthine oxidase in the ischemia + 0 livers was 7.5-folds higher than in the ischemia-treated livers.


CONCLUSIONS
NAC treatment of ischemia-reperfused livers, associated with GSH replenishment, prevents remote myocardial reperfusion injury. The role of NAC and GSH in reducing liver-associated oxidative burst propagation is discussed.
Weinbroum
A A
AA
Department of Anesthesiology, Critical Care Medicine, Tel Aviv Sourasky Medical Center, Israel. draviw@tasmc.health.gov.il
Kidron
A
A
Hochhauser
E
E
Hochman
A
A
Rudick
V
V
Vidne
B A
BA
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D005978:Glutathione; D000111:Acetylcysteine