To our knowledge postoperative hepatic hemodynamics and hepatic metabolism have not been fully studied on a long-term basis. Our goal was to develop a large animal model that would permit the measurement of hepatic blood flow (BF), perihepatic pressures (P), and hepatic metabolism in a long-term setting. Catheters were inserted into the jugular vein, carotid artery, pulmonary artery, hepatic vein, and portal vein (PV) of 27 commercially bred pigs; ultrasonic transit time flowmeter probes were placed around the hepatic artery and PV. Daily postoperative measurements of jugular vein P, carotid artery P, pulmonary artery P, hepatic vein P, and PVP, as well as hepatic artery BF and PVBF, were recorded for 20 days. Hepatic carbohydrate metabolism was assessed by arteriovenous difference techniques. Jugular vein P, pulmonary artery P, hepatic vein P, PVP, and heart rate reached steady-state values during the first week, with a mean +/- SEM of 1.0 +/- 0.3 mm Hg for jugular vein P, 21.4 +/- 2.1 mm Hg for pulmonary artery P, 4.3 +/- 0.4 mm Hg for HVP, 7.8 +/- 0.5 mm Hg for PVP, and 116 +/- 4 beats per minute for heart rate. Mean carotid artery P increased from 65 +/- 3 mm Hg during surgery to 94 +/- 2 mm Hg on postoperative day 1 (P < 0.001) and to a mean 101 +/- 2 mm Hg thereafter. Total hepatic BF reached a steady-state value of 1,132 +/- 187 ml/min by postoperative day 7 (P = 0.19). Over week 1 hepatic artery BF measured as a percentage of total hepatic BF decreased from 35.0 +/- 3.0% to 15.5 +/- 2.7%, and PVBF increased from 65.0 +/- 3.0% to 84.5 +/- 2.7% (P < 0.005); both variables were steady thereafter. In the hemodynamic steady state the net hepatic balances of glucose, lactate, glycerol, and alanine in 5 pigs were 9.9 +/- 4.0, -4.2 +/- 0.4, -2.3 +/- 1.1, and -0.68 +/- 0.22 micromol/kg per min respectively. The net gut (portal-drained viscera) balances of glucose, lactate, alanine, and glycerol were -2.0 +/- 2.5, 1.1 +/- 0.5, 0.73 +/- 0.18, and -0.69 +/- 0.19 micromol/kg per min respectively. Thus, a reliable large animal model was developed to study acute and chronic hepatic hemodynamics and metabolism.

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.