Ischemic versus pharmacologic hepatic preconditioning.
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.


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.
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.
Silvio Marcio Pegoraro
SM
Balzan
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.
Vinicius Grando
VG
Gava
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.
Alexandre
A
Rieger
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.
Daniel
D
Pra
Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil.
Luciano
L
Trombini
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.
Fernanda Fleig
FF
Zenkner
Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil.
Jorge André
JA
Horta
Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil.
Guaraci
G
Azambuja
Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil.
Luciano
L
Schopf
Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil.
Pedro Lucio
PL
de Souza
D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004249:DNA Damage; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000517:prevention & control*; D000077149:Sevoflurane; D013552:Swine; D000637:Transaminases / Q000378:metabolism; D052096:Warm Ischemia
D018685:Anesthetics, Inhalation; D015415:Biomarkers; D008738:Methyl Ethers; D000077149:Sevoflurane; D002097:C-Reactive Protein; D000637:Transaminases; D001663:Bilirubin
Ischemic preconditioning; Liver failure; Liver surgery; Pharmacologic preconditioning