The Period of Hyperbaric Oxygen Delivery Leads to Different Degrees of Hepatic Ischemia/Reperfusion Injury in Rats

Jose Carlos Chaves1, Murched Omar Taha2, Frederico Somaio Neto1, Adauto T. Ikejiri1, Paulo Bertoletto1, Roberto Teruya3, Manuel de Jesus Simoes2, Eduardo Hiroshi Tikazawa2, Fernando Lopes Carrara2, Jordan Bistafa Liu2, Djalma José Fagundes2.

1Surgery Department, Grande Dourados Federal University, Sao Paulo, Brazil;  2Surgery Department, Sao Paulo Federal University, Sao Paulo, Brazil;  3Surgery Department, Mato Grosso do Sul Federal University, Sao Paulo, Brazil email: taha@uol.com.br

INTRODUCTION

MATERIALS AND METHODS

RESULTS

CONCLUSIONS

Ischemia and reperfusion (IR) injury of the liver has been a significant health problem in terms of morbidity and mortality in many instances such as: liver transplant, cirrosis, hepatitis, neoplasia. The liver is sensitive to hypoxia and reperfusion effects which cause lesion of tissue by two different ways. First the polymorphonuclear interaction with the endothelial cells mediated by inflammatory cytokines and adhesion molecules, second the excessive production and release of oxygen radicals during reperfusion oxidative stress and apoptosis generator factor. One of procedure to avoid this damage is hyperbaric oxygen therapy which increase the supply of oxigygen during the ischemic period and reducing the deleterious effects of oxygen radicals. Beside the protective effect of the HBO, there is a potential exacerbation of oxidative stress associated with hyperoxia promoted by HBO, which effect in the reperfusion phase is considered the main aggressor cell during I/R. Our purpose is to evaluate the morphology of liver after ischemia/reperfusion and hyperbaric oxygen treatment (HBO).

Thirty-two male wistar rats (270–300 g) anesthetized with ketamine and xylazine subjected to 30 minutes of hepatic ischemia and 30 minutes of reperfusion were randomly distributed into four groups. The GIR (n=8), control without HBO; GHBO/I (n=8), in which HBO was applied only during the ischemia; GHBO/R (n=8), in which HBO was applied only during the reperfusion; or GHBO-IR (n=8), treated with HBO during both the ischemia and reperfusion. The hyperbaric oxygen (HBO) was carried out in an appropriate chamber for animal experimentation. Feasibility scores of hepatocytes have been determined by assessing eight items regarding liver injury. The differences in histological damage was determinated by ANOVA (p<0.05).

The histological injury of hepatic specimens was significantly lower when HBO was administered during the ischemia period-GHBO/I (79.0 ± 0.1), as compared to the GI/R (135.0 ± 0.1). HBO was not effective when applied during reperfusion-GHBO/R (151.3 ± 0.1) or during the ischemia plus reperfusion period-GHBO/IR (131.0 ± 0.1). The sum was significantly higher (P<0.05) in HBO-treated animals during the reperfusion period-GHBO/R when compared with any of the other groups.

A favorable effect was obtained when hyperbaric oxygen was administered early during ischemia. The hyperbaric oxygen in later periods of reperfusion was associated with a more severe sum index percentage of liver damage.

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1- Chaves JC , Fagundes DJ , Simões Mde J , Bertoletto PR , Oshima CT , Taha MO , Simões RS , AL Fagundes Hyperbaric oxygen therapy protects the liver from apoptosis caused by ischemia-reperfusion injury in rats. Microsurgery. 2009;29(7):578-83.2-Losada DM, Souza MEJ, Gomes MCJ, Picinato MANC, Fina CF, Feres O, Castro-e-Silva O. Hyperbaric oxygen therapy and ischemia and reperfusion: a valuable association to attenuate ischemic lesion and hepatic reperfusion. Acta Cir Bras. 2013;28(2):126-303- Caldeira DE, Souza ME, Gomes MC, Picinato MA, Fina CF, Feres O, Castro e Silva O. Effects of hyperbaric oxygen (HBO), as pre-conditioning in liver of rats submitted to periodic liver ischemia/reperfusion,. Acta Cir Bras. 2013;28(1):66-71. 4- Baldim LB, Nejo Jr R, Souza ME, Gomes MC, Picinato MA, Fina CF, Castro-e-Silva O. Effect of hyperbaric oxygen therapy on liver function during intermittent ischemia. Acta Cir Bras. 2013;28(1):61-5

Photomicrographs of liver tissue from the animals subjected to ischemia and reperfusion only (A), treated with HBO during the process of ischemia (B), treated with HBO during reperfusion (C) and treated with HBO during ischemia and reperfusion (D). Observe the congestion and dilation of the vein lobular center (CL). Arrows indicate apoptotic cells (H.E 200X).