The Effect of Ischemic Preconditioning Prior to Intraoperative Radiotherapy on Ischemic and on Reperfused Rat Liver

Hahn, Oszkár; Szijártó, Attila; Lotz, Gábor; Schaff, Zsuzsa; Vígváry, Zoltán; Váli, László; Kupcsulik, Péter Károly

doi:10.1016/j.jss.2006.10.026

« Previous Next »Journal of Surgical Research
Volume 142, Issue 1 , Pages 32-44, September 2007

The Effect of Ischemic Preconditioning Prior to Intraoperative Radiotherapy on Ischemic and on Reperfused Rat Liver

Oszkár Hahn, M.D.
- First Department of Surgery, Semmelweis University, Budapest, Hungary
- To whom correspondence and reprint requests should be addressed at First Department of Surgery, Semmelweis University, Budapest 1082, Hungary.
Attila Szijártó, M.D.
- First Department of Surgery, Semmelweis University, Budapest, Hungary
Gábor Lotz, M.D.
- Second Department of Pathology, Semmelweis University, Budapest, Hungary
Zsuzsa Schaff, D.S.C.
- Second Department of Pathology, Semmelweis University, Budapest, Hungary
Zoltán Vígváry, D.S.C.
- Department of Radiology, Semmelweis University, Budapest, Hungary
László Váli, M.D.
- Second Department of Internal Medicine, Semmelweis University, Budapest, Hungary
Péter Károly Kupcsulik, D.S.C.
- First Department of Surgery, Semmelweis University, Budapest, Hungary

Received 13 April 2006 published online 15 July 2007.

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.

Materials and 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-α 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.

Key Words: intraoperative radiotherapy, ischemia, reperfusion, preconditioning, liver