Suppression of liver allograft rejection by administration of 15-deoxyspergualin. Comparison of administration via the hepatic artery, portal vein, or systemic circulation.
In this experiment, the effect of the administration route-the hepatic artery, portal vein, or systemic circulation-of the immunosuppressive drug 15-deoxyspergualin (DSG) on the suppression of liver allograft rejection is investigated. A 3-day injection of DSG at a dose of 0.32-1.28 mg/kg per day into the systemic circulation of a rat that had received a liver transplant was not effective in prolonging liver graft survival (14.3 +/- 2.9 days vs. 14.1 +/- 2.5 days for controls). However, the administration of DSG into the portal vein following liver transplantation markedly prolonged survival for up to 24.9 +/- 10.0 days. Survival times were prolonged even more when the DSG was administered via the hepatic artery for 3 successive days after liver grafting (30.9 +/- 9.6 days). The concentration of DSG in the blood following the one-shot injection of DSG was highest when DSG was administered via the hepatic artery, intermediate when injected into the portal vein, and lowest when injected into the systemic vein. In conclusion, DSG can inhibit liver graft rejection more effectively via the hepatic arterial route than via the portal vein or systemic circulation.
Yano
K
K
Second Department of Surgery, School of Medicine, Hiroshima University, Japan.
Fukuda
Y
Y
Sumimoto
R
R
Sumimoto
K
K
Ito
H
H
Dohi
K
K
D000818:Animals; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006146:Guanidines / Q000008:administration & dosage* / Q000494:pharmacology; D006499:Hepatic Artery / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology; D008297:Male; D011169:Portal Vein / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew
D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus