Protection by cyclosporine A against normothermic liver ischemia-reperfusion in pigs.
BACKGROUND
Cyclosporine A (CYA) is primarily utilized as an immunosuppressant, but its mechanisms of action (including decreased neutrophilic free radical production and stabilization of mitochondrial and lysosomal membranes) may have beneficial effects in ischemia and reperfusion (IR) injury. This study was undertaken to examine the effect of CYA pretreatment on porcine liver histopathologic changes and enzymatic release caused by ischemia and reperfusion.


METHODS
CYA was administered orally for 4 days prior to surgery in two doses (10 or 20 mg/kg) while controls received only the control vehicle. Pigs were then exposed to 4 h of hepatic ischemia followed by 2 h of reperfusion.


RESULTS
Significant decreases in AST levels compared to controls were seen in high dose CYA pigs at the end of ischemia and at 30-min intervals during the reperfusion period. Controls exhibited necrotic hepatocytes and severe inflammatory cell infiltration, while high dose CYA animals demonstrated mild inflammatory cell infiltrates. Controls had decreased survival--20% did not survive reperfusion.


CONCLUSIONS
This study indicates that CYA may be useful in decreasing initial damage resulting from warm hepatic IR injury.
Travis
D L
DL
Baylor University Medical Center, Transplant Services, Dallas, Texas 75246, USA.
Fabia
R
R
Netto
G G
GG
Husberg
B S
BS
Goldstein
R M
RM
Klintmalm
G B
GB
Levy
M F
MF
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006499:Hepatic Artery / Q000187:drug effects / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007511:Ischemia / Q000201:enzymology* / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology*; D013696:Temperature
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase