A method for hepatic arterial perfusion studies in the rat.
The current model for selective hepatic arterial infusion therapy was evaluated for its suitability for short-term pharmacokinetic experiments. This preparation consists of selective cannulation of the common hepatic artery via the gastroduodenal artery of the rat. Radioactive microspheres were injected to determine hepatic or extrahepatic sites of perfusion. Radioactive microsphere determination of hepatic arterial flow and cardiac output were also performed. Our data indicate that at high flow rates (2 ml/min), significant loss of drug would occur due to retrograde flow. Modification of the model to include temporary proximal hepatic artery occlusion ensures hepatic delivery of greater than 95% of drug. Furthermore, temporary hepatic artery occlusion does not alter cardiac output or hepatic arterial blood flow. Selective hepatic arterial infusion in rats with synchronous temporary hepatic artery occlusion is an adequate model for short-term pharmacokinetic studies.
Than
T T
TT
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Sitzmann
J V
JV
Li
S S
SS
Lin
P W
PW
Grochow
L B
LB
D000818:Animals; D006439:Hemodynamics; D006499:Hepatic Artery / Q000502:physiology*; D007261:Infusions, Intra-Arterial / Q000379:methods*; D008026:Ligation; D008297:Male; D008863:Microspheres; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow