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 t he treatment of primary nonfunction of hepatic allografts and fulminan t 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 adminis tration has not been determined. Thus, we measured plasma PGE(1) conce ntrations in patients with hepatic dysfunction being treated with PGE( 1) and in a swine model of PGE(1) infusion. We also determined the hem odynamic effects of PGE(1) infusion in swine, Blood was sampled from t he 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 splan chnic 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, eve n 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 intra venous PGE(1) for hepatic dysfunction (0.11-1.30 mu g/kg/hr) had a pul monary extraction ratio of 0.69+/-0.17, Systemic arterial concentratio ns of PGE(1) were less than or equal to 62 pg/ml, These results sugges t that due to clearance of PGE(1) in the pulmonary and splanchnic circ ulations, current clinical protocols for intravenous administration of PGE(1) are not likely to affect perihepatic hemodynamics.