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. 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-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.

Effect of ischemic preconditioning on rat liver microcirculation monitored with laser Doppler flowmetry.

BACKGROUND: Ischemic preconditioning (IP) may protect the liver from ischemia-reperfusion (I-R) injury during liver resection. This study investigated the effect of IP on hepatic microcirculation (HM) and analyzed the objective parameters of the HM using laser Doppler flowmetry (LDF). METHODS: We used male Wistar rats (250-280 g) that underwent normothermic, segmental liver ischemia. The animals were divided into eight groups: 30, 45, 60, and 90 min of ischemia with, or without, IP. Five minutes ischemia and 10 min reperfusion, in two cycles, were used to elicit IP. Changes of the hepatic microcirculation were studied by LDF with on-line computer monitoring and processing. Histological alterations, liver enzymes, bilirubin, and TNF-alpha level were all measured simultaneously. RESULTS: Reperfusion was assessed by post-ischemia flux plateau maximum (PM) and by the area under the reperfusion-curve (RA). Both PM and RA are inversely correlated with the duration of ischemia. The groups with IP had significantly (P < 0.05) higher flow values than groups without preconditioning. IP before liver ischemia resulted in significantly (P < 0.05) lower TNF-alpha levels at the end of the 30-min reperfusion. Lower serum ALT, LDH, and bilirubin levels could only be observed at 45 and 60 min I-R during the first post-operative day. On the seventh post-operative day there were no significant differences between the I-R and IP + IR groups in any of these parameters. CONCLUSION: The benefit of ischemic preconditioning on hepatic microcirculation was well demonstrated with this method, which has never been described before, in this context. Changes in hepatic microcirculation can be precisely investigated by laser Doppler flowmetry using the standardization and transformation described in this paper.