Plasma prostaglandin E(1) concentrations and hemodynamics during intravenous infusions of prostaglandin E(1) in humans and swine

Prostaglandin (PG) E(1) administered intravenously has been used for the treatment of primary nonfunction of hepatic allografts and fulminant hepatic failure. It has been proposed that this therapy may improve hepatic blood flow via the vasodilating properties of PGE(1), However, PGE(1) undergoes extensive metabolic inactivation by the lung and the concentration of PGE(1) reaching the liver during intravenous administration has not been determined. Thus, we measured plasma PGE(1) concentrations in patients with hepatic dysfunction being treated with PGE(1) and in a swine model of PGE(1) infusion. We also determined the hemodynamic effects of PGE(1) infusion in swine, Blood was sampled from the pulmonary artery, carotid artery, portal vein, and hepatic vein in swine infused with PGE(1) (range, 0.67-4.9 mu g/kg/hr) demonstrating: (1) a pulmonary extraction ratio of PGE(1) of 0.78+/-0.12, (2) a splanchnic extraction ratio of PGE(1) of 0.54+/-0.23, and (3) levels of PGE(1) in the systemic circulation of less than or equal to 78 pg/ml, even at the highest infusion rates. Despite significant increases in body temperature and pulse rate, hepatic hemodynamics were not affected by the PGE(1) infusions in healthy swine, Seven patients receiving intravenous PGE(1) for hepatic dysfunction (0.11-1.30 mu g/kg/hr) had a pulmonary extraction ratio of 0.69+/-0.17, Systemic arterial concentrations of PGE(1) were less than or equal to 62 pg/ml, These results suggest that due to clearance of PGE(1) in the pulmonary and splanchnic circulations, current clinical protocols for intravenous administration of PGE(1) are not likely to affect perihepatic hemodynamics.