[Methods of increasing ischemic tolerance in liver surgery].
The author evaluates an experimental model of hepatic resection. The goal of the study was to investigate ischaemic tolerance during liver resection. In this model, we also investigated the protective effects of ischemic preconditioning (IP), a PARP enzyme inhibitor (PJ-34), and an antioxidant glutamine (Gln). Inbred male Wistar rats were used for the experiments. Complete segmental ischaemia of the liver was achieved with or without using IP, PJ-34 or Gln pretreatment before the ischaemia. Microcirculation was monitored using laser Doppler flowmeter (LDF) throughout the ischaemia-reperfusion period. Required standardizations and mathematical analyses were performed in order to validate statistical analysis. Histological changes, immunohistochemistry (TUNEL, caspase), liver enzymes, bilirubin, and TNF-alpha levels were all measured simultaneously.


CONCLUSIONS
30 minutes ischaemia was well tolerated by the liver and IP does not cause further improvement. 45 to 60 minutes ischaemia resulted in serious microcirculatory changes during reperfusion. 90 minutes ischaemia was unequivocally intolerable. The liver injury and microcirculatory changes caused by 45 or 60 minutes of ischemia could be reduced with IP. Improvement was observed both on histology and in survival rates. After 45 and 60 minutes, IP + I-R caused a significant decline in the TNF-alpha levels. IP, PJ-34 PARP-inhibitor and glutamine pretreatment prior to 60 minutes of ischaemia resulted in an improvement of microcirculation. Immunohistochemistry for activated caspase-3 demonstrated significantly higher apoptosis rates in the PJ-34 PARP-inhibitor and glutamine-pretreated groups, in contrast to the sham and I-R groups. Antioxidant levels in the serum and in the liver homogenates showed significant improvement in the IP and glutamine-pretreated groups.
Szijártó
Attila
A
Semmelweis Egyetem I. sz. Sebészeti Klinika 1082 Budapest Ulloi út 78. szijartoattila@gmail.com
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology*; D006498:Hepatectomy / Q000379:methods*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019194:Ischemic Preconditioning / Q000379:methods*; D017078:Laser-Doppler Flowmetry; D008099:Liver / Q000098:blood supply / Q000201:enzymology; D008102:Liver Circulation; D008111:Liver Function Tests; D008297:Male; D008833:Microcirculation; D010616:Phenanthrenes / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D053148:Caspase 3