title: V-PYRRO/NO: an hepato-selective nitric oxide donor improves porcine liver hemodynamics and function after ischemia reperfusion.
abstract: BACKGROUND
  The role of nitric oxide (NO) in ischemia reperfusion (I/R) injury is controversial as both beneficial and harmful effects have been reported. We explored the potential role of a pharmacological agent recently shown to generate NO metabolically in the liver in an animal model of transplantation.
  
  
  METHODS
  The effect of a selective hepatic NO donor, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), on hepatic hemodynamics and biliary function was evaluated in both the in situ and I/R pig liver.
  
  
  RESULTS
  V-PYRRO/NO significantly reduced in situ hepatic vascular resistance (HVR) without altering systolic blood pressure. Portal vein flow was essentially unchanged during in situ infusions while hepatic artery flow nearly doubled (P=0.03). After I/R, V-PYRRO/NO infusions significantly reduced both portal vein pressure (PVP) and HVR (P=0.04). Also, serum bile acid clearance increased from 15% when taurocholate (TC) was infused alone to 46% (P=0.007) when infused simultaneously with V-PYRRO/NO. Aqueous bile production tripled with TC and V-PYRRO/NO as compared to TC alone (P=0.04). Analysis of bile outputs revealed a significant increase in biliary cholesterol, biliary phospholipid, and biliary bile acid (P<0.05) with V-PYRRO/NO infusion.
  
  
  CONCLUSIONS
  The hepato-selective nitric oxide donor, V-PYRRO/NO, reduced hepatic resistance parameters of the pig liver both before and after I/R and improved the plasma clearance of bile acid and biliary outputs of bile acid-dependent compounds. The augmented function observed after I/R may be due to improvements in hepatic blood flow secondary to altered hepatic hemodynamics.
authors.affiliation: Department of Surgery, University of Massachusetts Medical School, North Worcester 01655, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ricciardi
authors.forename: D P
authors.initials: DP
authors.lastname: Foley
authors.forename: S H
authors.initials: SH
authors.lastname: Quarfordt
authors.forename: J E
authors.initials: JE
authors.lastname: Saavedra
authors.forename: L K
authors.initials: LK
authors.lastname: Keefer
authors.forename: S M
authors.initials: SM
authors.lastname: Wheeler
authors.forename: S E
authors.initials: SE
authors.lastname: Donohue
authors.forename: M P
authors.initials: MP
authors.lastname: Callery
authors.forename: W C
authors.initials: WC
authors.lastname: Meyers
mesh_terms: D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000502:physiology; D011355:Prodrugs / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D015427:Reperfusion Injury / Q000503:physiopathology; D013552:Swine
chemical_list: C107010:O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate; D011355:Prodrugs; D011759:Pyrrolidines