title: Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions.
abstract: Immediately after hepatic reperfusion in human orthotopic liver transplantation, high amounts of arginase are released from the graft, thereby influencing nitric oxide metabolism. This metabolic alteration may be one component of the ischemia-reperfusion syndrome in OLT with its hemodynamic disturbances (e.g., systemic hypotension, pulmonary hypertension). The aim of this study was to compare hemodynamic and metabolic changes following OLT in the pigs with those obtained under arginase infusions in catheterized, anesthetized pigs. Following liver revascularization in the pigs, plasma arginase concentrations increased from 48 +/- 19 IU/L to 2613 +/- 944 IU/L, resulting in a drop in plasma levels of L-arginine (-87%) and in a drop in nitrite (-82%) and nitrate (-53%) concentrations. Of the measured organ-specific hemodynamic alterations, the mean pulmonary arterial pressure increased from 17 +/- 2 mmHg to 30 +/- 5 mmHg, whereas the flow/pressure index of the portal vein decreased about 60%. A primed continuous infusion of arginase (25,000 IU) increased plasma arginase levels to a maximum of 3,690 +/- 962 IU and evoked a decrease of L-arginine, but did not alter plasma nitrite or nitrate levels. The administration of arginase in healthy pigs did not influence cardiac output, mean arterial pressure, heart rate, or total peripheral resistance, but led to an increase of mean pulmonary arterial pressure from 19 +/- 3 to 48 +/- 5 mmHg and to a reduction of arterial hepatic blood flow from 229 +/- 65 ml/min to 154 +/- 41 ml/min. From this we conclude that high levels of liver arginase cause hemodynamic alterations in the lung and the liver. We hypothesize that the pulmonary hypertension and the reduced hepatic blood flow found during the immediate reperfusion period after OLT are possibly related to the increased arginase release due to the hepatic damage of the graft.
authors.affiliation: Department of Transplantation, University of Vienna, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Längle
authors.forename: E
authors.initials: E
authors.lastname: Roth
authors.forename: R
authors.initials: R
authors.lastname: Steininger
authors.forename: S
authors.initials: S
authors.lastname: Winkler
authors.forename: F
authors.initials: F
authors.lastname: Mühlbacher
mesh_terms: D000818:Animals; D001119:Arginase / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D008099:Liver / Q000201:enzymology*; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D015427:Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D013552:Swine
chemical_list: D001119:Arginase