The effect of ischemic preconditioning prior to intraoperative radiotherapy on ischemic and on reperfused rat liver.
BACKGROUND
The purpose of this study was to increase the tolerance of the liver to radiation injury with the proven effect of ischemic precondition (IP) in decreasing oxygen-derived free radicals, and to compare the effect of intraoperative radiotherapy (IORT) during ischemia and during reperfusion on rat liver.


METHODS
Two hundred fifty to 280 g male Wistar rats underwent 45 min of normothermic, segmental liver ischemia with or without IP/5 min ischemia and 10 min reperfusion, in two cycles. During ischemia or reperfusion, IORT doses of 0, 25, or 50 Gy were applied to the ischemic liver lobe. Hepatic microcirculation was monitored by laser Doppler flowmeter. Short- and long-term histological, alkaline phosphatase, bilirubin and tumor necrosis factor-alpha levels, liver tissue, and serum antioxidant alterations were measured.


RESULTS
Histological, laboratory, as well as flowmetry alterations caused by 25 Gy were reversible after 6 mo. Three mo following IORT, histological examination revealed parenchymal fibrosis, bridging, liver cell atrophy, and bile duct proliferation in the group that was irradiated with 50 Gy during reperfusion, without IP. In this group, the changes were present 6 mo following IORT, and also the levels of tumor necrosis factor-alpha and oxygen-derived free radicals after reperfusion were increased. All these changes were significantly milder in groups with IP, especially those that were irradiated during ischemia.


CONCLUSIONS
IORT to the liver, up to 25 Gy, can be applied without short- or long-term treatment morbidity. Doses of up to 50 Gy are tolerated with IP, which has never been described before. Irradiation during ischemia is less toxic for the liver tissue.
Hahn
Oszkár
O
First Department of Surgery, Semmelweis University, Budapest, Hungary. ohahn@freemail.hu
Szijártó
Attila
A
Lotz
Gábor
G
Schaff
Zsuzsa
Z
Vígváry
Zoltán
Z
Váli
László
L
Kupcsulik
Péter Károly
PK
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005609:Free Radicals / Q000378:metabolism; D007432:Intraoperative Period; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000293:injuries* / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D011832:Radiation Injuries / Q000517:prevention & control*; D011878:Radiotherapy / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000532:radiotherapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005609:Free Radicals; D014409:Tumor Necrosis Factor-alpha; D000469:Alkaline Phosphatase; D001663:Bilirubin