Plasma Prostaglandin E1 Concentrations and Hemodynamics During Intravenous Infusions of Prostaglandin E1 in Humans and Swine1

Abstract

Prostaglandin (PG) E1 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 PGE1. However, PGE1 undergoes extensive metabolic inactivation by the lung and the concentration of PGE1 reaching the liver during intravenous administration has not been determined. Thus, we measured plasma PGE1 concentrations in patients with hepatic dysfunction being treated with PGE1 and in a swine model of PGE1 infusion. We also determined the hemodynamic effects of PGE1 infusion in swine. Blood was sampled from the pulmonary artery, carotid artery, portal vein, and hepatic vein in swine infused with PGE1 (range, 0.67-4.9 microg/kg/hr) demonstrating: (1) a pulmonary extraction ratio of PGE1 of 0.78 +/- 0.12, (2) a splanchnic extraction ratio of PGE1 of 0.54 +/- 0.23, and (3) levels of PGE1 in the systemic circulation of </= 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 PGE1 infusions in healthy swine. Seven patients receiving intravenous PGE1 for hepatic dysfunction (0.11-1.30 microg/kg/hr) had a pulmonary extraction ratio of 0.69 +/- 0.17. Systemic arterial concentrations of PGE1 were </= 62 pg/ml. These results suggest that due to clearance of PGE2 in the pulmonary and splanchnic circulations, current clinical protocols for intravenous administration of PGE1 are not likely to affect perihepatic hemodynamics.

trans-10,cis-12-Conjugated Linoleic Acid Instigates Inflammation in Human Adipocytes Compared with Preadipocytes

“…Quantification of PGE 2 and PGF 2 -PGE 2 and PGF 2 were measured with a stable isotope dilution gas chromatographic/ negative ion chemical ionization/mass spectrometric (GC/ NICI/MS) assay (38). Briefly, PGE 2 -d 4 (2.12 ng) and PGF 2 -d 4 (0.84 ng) internal standards were added to the media samples.…”

Efficacy of continuous infusion of prostaglandin E1 through the superior mesenteric artery against ischemic liver cell necrosis after hepatic artery occlusion

“…The PVF increase in the SMA group was caused by an increased SMA flow, whereas PGE 1 concentration in systemic circulation became too low to influence SMA flow in the IV and PV groups. This is attributable to high inactivation rates of PGE 1 in the lungs (23) and livers (24). Moreover, an increase in PVF in the SMA group produced an increase in the oxygen content of portal blood.…”

Prostaglandin E₁ Continuous Hepatic Arterial Infusion in the Treatment of Postoperative Acute Liver Failure

“…On the other hand, a recent report by Awad et al [6]demonstrated that current clinical protocols for intravenous administration of PGE 1 did not raise plasma concentrations of PGE 1 sufficiently and were not likely to affect perihepatic hemodynamics at such a dosage. From our results, at a rate of 0.1 µg/kg/min in pigs, hepatic arterial flow increased markedly when given intra-arterially, while it increased slightly when given intravenously.…”

“…In treating such severe liver damage, prostaglandin E 1 (PGE 1 ) has attracted attention for its various kinds of protective effects [3, 4]. However, it is known that approximately 70% of PGE 1 is inactivated during a single passage through the lung [5, 6]. Therefore, direct infusion of this drug into the bloodstream in the liver might be more beneficial than systemic intravenous infusion.…”