title: The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats.
abstract: OBJECTIVE
  Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats.
  
  
  METHODS
  To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (TC), IP, and intermittent clamping (IC). Ischemic injury was induced by clamping the left portal pedicle including the portal vein and hepatic artery. Liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to assess liver damage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining for apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell replication were also performed.
  
  
  RESULTS
  Day-1 ALT and AST were highest in IP, however, levels in NC and IC were comparably low on days 1-7. There was no significant correlation of AST or ALT with experimental groups (P=0.615 and P=0.186). On TUNEL, numbers of apoptotic cells at 100× magnification (cells/field) were 31.8±24.2 in NC, 69.0±72.3 in TC, 80.2±63.1 in IP, and 21.2±20.8 in IC (P<0.05). When regeneration capacity was assessed by PCNA staining, PCNA-positive cells (cells/field) at 400× were 3.4±6.0 in NC, 16.9±69 in TC, 17.0±7.8 in IP and 7.4±7.6 in IC (P<0.05).
  
  
  CONCLUSIONS
  Although regeneration capacity in IP is higher than IC, the liver is vulnerable to ischemic damage in cirrhotic rats. Careful consideration is needed in applying IP in the clinical setting.
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seon Ok
authors.initials: SO
authors.lastname: Min
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Lee
authors.forename: Jin A
authors.initials: JA
authors.lastname: Cho
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Kim
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D003250:Constriction; D006498:Hepatectomy / Q000379:methods; D006499:Hepatic Artery; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D008115:Liver Regeneration; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000201:enzymology / Q000473:pathology; D013853:Thioacetamide / Q000633:toxicity
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D013853:Thioacetamide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase