Altered hepatic hemodynamics and improved liver function following intrahepatic vascular infusion of prostaglandin E1

Abstract

Prostaglandin E1 (PGE1) has cytoprotective effects in the liver. To find how PGE1 influenced hepatic hemodynamics, oxygen metabolism, and hepatic function, we carried out an experimental and a clinical study. PGE1 was continuously administered into the hepatic artery (n = 5) or portal vein (n = 5) at a rate of 0.01 micrograms/kg per min in healthy mongrel dogs. In the clinical study, in eight patients PGE1 was administered through the hepatic artery at a rate of 0.01 micrograms/kg per min after hepatic lobectomy. In the experimental study, hepatic hemodynamics and oxygen metabolism did not change during the administration of PGE1 into the portal vein. During administration of PGE1 into the hepatic artery, hepatic arterial flow increased 1.5-fold after administration compared to the rate before administration (P < 0.01). Hepatic arterial pressure, hepatic arterial resistance, and post-sinusoidal resistance significantly decreased after administration (P < 0.01, P < 0.01, and P < 0.05, respectively). Hepatic oxygen supply increased significantly (P < 0.01). In the patients, serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels remained low after surgery, and the recovery of protein synthesis was improved compared with that in eight hepatectomized patients without PGE1 administration (controls). The intrahepatic arterial infusion of PGE1 was considered useful for the recovery of liver function.

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

“…In spite of a slight decrease of portal blood flow, probably caused by the reciprocal self-regulation of the liver blood flow [17], there was a significant increase in hepatic blood flow in the case of hepatic arterial infusion of PGE 1 . These experimental results are consistent with those reported by Nakai et al [9], in spite of differences in the dosage and animal. They also observed a decrease in hepatic arterial pressure and hepatic arterial resistance accompanying hepatic arterial infusion of PGE 1 , which implicated the direct vasodilatory effect of the drug on the vascular smooth muscles.…”

“…Therefore, direct infusion of this drug into the bloodstream in the liver might be more beneficial than systemic intravenous infusion. This can be achieved in one of two ways: via the portal vein [7, 8]or via the hepatic artery [9, 10]. The creation of an access route to the portal vein involves certain risks; on the other hand, an access route to the hepatic artery can be constructed relatively safely, so hepatic arterial infusion could be of more practical use than intraportal infusion in treating severe liver damage.…”

Anti‐inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation

“…To improve flow properties by vasodilatation, a bolus of BQ123 at both perfusion initiation and after 2 hours (1.25 mg; AG Scientific, Kelowna, BC, Canada) were used. Also, a continuous infusion of prostaglandin E1 (500 μg/3 hours; Pfizer, Kirkland, QC, Canada) was administrated for its anti‐inflammatory property as described . Acetylcysteine (6 g; Sandoz, Quebec, QC, Canada) was added for its radical scavenging properties.…”

“…Also, a continuous infusion of prostaglandin E1 (500 lg/3 hours; Pfizer, Kirkland, QC, Canada) was administrated for its anti-inflammatory property as described. (13) Acetylcysteine (14) (6 g; Sandoz, Quebec, QC, Canada) was added for its radical scavenging properties. A gas composition containing 95% O 2 and 5% CO 2 was connected to the oxygenator at a sweep of 2 L/minute.…”

Subnormothermic ex vivo liver perfusion is a safe alternative to cold static storage for preserving standard criteria grafts

“…Also, 1 g of cefazolin (Pharmaceutical Partners of Canada, Richmond Hill, ON, Canada) and 500 mg of metronidazole (Baxter, Mississauga, ON, Canada) were added to prevent bacterial contamination. To improve flow properties by vasodilatation, a bolus of BQ‐123 at both perfusion initiation and after 1.5 hours (1.25 mg, AG Scientific, Kelowna, BC, Canada) and a continuous infusion of 500 µg/3 hours of alprostadil (Pfizer, Kirkland, QC, Canada) were used. Also, 6 g of acetylcysteine (Sandoz, Quebec, QC, Canada) was added for its radical scavenging properties.…”