V-PYRRO/NO: An hepato-selective nitric oxide donor improves porcine liver hemodynamics and function after ischemia reperfusion

• Published in: Transplantation Vol. 71; no. 2; pp. 193 - 198
• Main Authors: RICCIARDI, Rocco, FOLEY, David P, QUARFORDT, Steven H, SAAVEDRA, Joseph E, KEEFER, Larry K, WHEELER, Suzanne M, DONOHUE, Susan E, CALLERY, Mark P, MEYERS, William C
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 27-01-2001
• Subjects: Animals; Biological and medical sciences; Hemodynamics - drug effects; Liver - physiology; Liver, biliary tract, pancreas, portal circulation, spleen; Medical sciences; Prodrugs - pharmacology; Pyrrolidines - pharmacology; Reperfusion Injury - physiopathology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Swine; Liver; Cardiovascular disease; Transplantation; Prodrug; Homotransplantation; Metabolism; Pig; Liver function; Vertebrata; Chemotherapy; Mammalia; Reperfusion; Treatment; Ischemia; Surgery; Animal; Nitric oxide; Artiodactyla; Hemodynamics; Experimental surgery; Ungulata
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/00007890-200101270-00004

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.
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.
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.
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.