Silvio Marcio Pegoraro Balzan1, Vinicius Grando Gava2, Alexandre Rieger3, Daniel Pra3, Luciano Trombini4, Fernanda Fleig Zenkner5, Jorge André Horta4, Guaraci Azambuja4, Luciano Schopf4, Pedro Lucio de Souza4. 1. Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil; Department of Surgery, Moinhos de Vento Hospital, Porto Alegre, Brazil. Electronic address: sbalzan@hotmail.com. 2. Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil; Department of Surgery, Moinhos de Vento Hospital, Porto Alegre, Brazil. 3. Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil; Department of Biology and Pharmacy, Postgraduation Course of Health Promotion, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil; Laboratory of Biotechnology and Genetics, Department of Biology and Pharmacy, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil. 4. Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil. 5. Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil; Laboratory of Biotechnology and Genetics, Department of Biology and Pharmacy, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil.
Abstract
BACKGROUND: Hepatic ischemia-reperfusion injury has a significant impact on liver resection and transplantation. Many strategies have been developed to reduce the effects of ischemia-reperfusion injury, including pharmacologic and ischemic preconditioning; however, studies comparing these two methods are lacking. MATERIAL AND METHODS: An experimental study was performed in a swine model. Eighteen swine were randomly assigned to three different groups: an ischemic preconditioning (IschPC) group, a pharmacologic preconditioning (PharmPC) group, and a control group. All animals underwent a 40-min liver ischemia, followed by 40 min of reperfusion. The IschPC group received a short period of ischemia (10 min) and a short period of reperfusion (15 min) before prolonged ischemia. The PharmPC group received inhaled sevoflurane for 30 min before prolonged ischemia. The control group did not receive any intervention before prolonged ischemia. Blood samples and liver tissue were obtained after ischemic and reperfusion periods. Injury was evaluated by measure of DNA damage (using COMET assay) and serum biochemical markers (transaminases, alkaline phosphatase, amylase, bilirubin, and C-reactive protein [CRP]). RESULTS: No significant difference was found in serum biochemical markers, except for the C-reactive protein level that was lower in the PharmPC group than in the control group soon after hepatic ischemia. Soon after prolonged ischemia, DNA damage index, both in blood samples and in liver tissue samples, was similar among the groups. However, an increase in DNA damage after reperfusion was higher in the control group than in the PharmPC group (P < 0.05). The increase in DNA damage in the IschPC group was half of that observed in the control, but this difference was not statistically significant. CONCLUSIONS: Our results suggest an early protective effect of PharmPC (lower levels of C-reactive protein soon after ischemia). The protective effect observed after reperfusion was higher with PharmPC than with ischemic preconditioning. The simultaneous use of both methods could potentiate protection for ischemia-reperfusion.
BACKGROUND: Hepatic ischemia-reperfusion injury has a significant impact on liver resection and transplantation. Many strategies have been developed to reduce the effects of ischemia-reperfusion injury, including pharmacologic and ischemic preconditioning; however, studies comparing these two methods are lacking. MATERIAL AND METHODS: An experimental study was performed in a swine model. Eighteen swine were randomly assigned to three different groups: an ischemic preconditioning (IschPC) group, a pharmacologic preconditioning (PharmPC) group, and a control group. All animals underwent a 40-min liver ischemia, followed by 40 min of reperfusion. The IschPC group received a short period of ischemia (10 min) and a short period of reperfusion (15 min) before prolonged ischemia. The PharmPC group received inhaled sevoflurane for 30 min before prolonged ischemia. The control group did not receive any intervention before prolonged ischemia. Blood samples and liver tissue were obtained after ischemic and reperfusion periods. Injury was evaluated by measure of DNA damage (using COMET assay) and serum biochemical markers (transaminases, alkaline phosphatase, amylase, bilirubin, and C-reactive protein [CRP]). RESULTS: No significant difference was found in serum biochemical markers, except for the C-reactive protein level that was lower in the PharmPC group than in the control group soon after hepatic ischemia. Soon after prolonged ischemia, DNA damage index, both in blood samples and in liver tissue samples, was similar among the groups. However, an increase in DNA damage after reperfusion was higher in the control group than in the PharmPC group (P < 0.05). The increase in DNA damage in the IschPC group was half of that observed in the control, but this difference was not statistically significant. CONCLUSIONS: Our results suggest an early protective effect of PharmPC (lower levels of C-reactive protein soon after ischemia). The protective effect observed after reperfusion was higher with PharmPC than with ischemic preconditioning. The simultaneous use of both methods could potentiate protection for ischemia-reperfusion.