title: Atrial natriuretic peptide reduces hepatic ischemia-reperfusion injury in rabbits.
abstract: OBJECTIVE
  Atrial natriuretic peptide (ANP) has been known to be protective against hepatic ischemia/reperfusion injury. The purpose of this study was to verify the hypothesis that ANP conserves microvascular circulation and reduces ischemia-reperfusion injury in the in vivo rabbit model.
  
  
  METHODS
  With IRB approval, 30 male Japanese white rabbits under pentobarbital anesthesia were studied. These animals were randomly assigned to the following three groups (n = 10 each): control, ANP, and sham group. Animals in the ANP group received continuous infusion of ANP at 0.1 μg/kg/min throughout the study period. Animals in control and ANP groups underwent 90 min of partial hepatic ischemia by clamping the right hepatic artery and portal vein. Descending aortic blood flow (AoF) was monitored with a transit-time ultrasound flowmeter. Hepatic tissue microvascular blood flow (HTBF) at both right (ischemic) and left (nonischemic) lobe was intermittently evaluated with the hydrogen clearance method. After 180 min of reperfusion, hepatic injury was determined with serum AST and ALT. Galactose clearance of reperfused right lobe was also measured as an indicator of hepatic metabolic function. Histopathological change and the number of apoptotic hepatocytes were also evaluated.
  
  
  RESULTS
  Systemic hemodynamic data including mean arterial pressure, heart rate, and AoF did not differ among the three groups during the study period. ANP attenuated ischemia-induced right HTBF decrease. ANP also suppressed histopathological degeneration, apoptosis, and decline in galactose clearance after reperfusion.
  
  
  CONCLUSIONS
  ANP attenuated hepatic microvascular dysfunction and hepatocyte injury after reperfusion without significant hemodynamic change.
authors.affiliation: Department of Anesthesiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan, yamada@e-ml.jp.
authors.forename: Takashige
authors.initials: T
authors.lastname: Yamada
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kotake
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Nagata
authors.forename: Junzo
authors.initials: J
authors.lastname: Takeda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D062186:Arterial Pressure / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology*; D005690:Galactose / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D011817:Rabbits; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D009320:Atrial Natriuretic Factor; D005690:Galactose