Application of maximal removal rate of indocyanine green to the determination of hepatic functional mass in conscious rats.
We established a versatile method for the measurement of indocyanine green maximal removal rate (ICG Rmax) to detect hepatic functional mass in conscious rats using a repeated blood sampling procedure. On investigation of the optimal technical conditions, the appropriate intravenous administered doses of ICG were 2.5, 5, 10 or 20 mg/kg, and the best blood collection times for calculating plasma half-life at these doses were immediately before, and 4, 7 and 10 min after ICG injection. The interval among the respective ICG injections was more than 4 hr. In hepatectomized rats, the ICG Rmax value was reduced to about 50% and 20% of sham-operated rats in mean 2/3 and 4/5 liver resections, respectively, suggesting that it would almost extrapolate to hepatic surviving reserves under these experimental conditions. In rats treated subcutaneously with carbon tetrachloride (CCl4, 0.1 and 0.25 ml/kg) thrice weekly during a 17-week period (120 days), a decrease in ICG Rmax value did not correlate with increases in serum alanine transaminase (ALT), alkaline phosphatase (ALP) and total bilirubin values throughout the experimental periods. However, the reduced ICG Rmax well correlated with decreases in serum albumin and cholinesterase (CHE) values from day 50. Histological examinations in the liver revealed that nodules of hepatocytes were separated by thick fibrous bands, defining the typical aspect of cirrhosis on day 30 to 90. These results suggest that the measurement of ICG Rmax is a valuable tool for the estimation of hepatic functional integrity in rats.
Inage
F
F
Tokyo Research and Development Center, Daiichi Pharmaceutical Co., Ltd., Japan.
Furuhama
K
K
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000097:blood / Q000503:physiopathology; D002802:Cholinesterases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006498:Hepatectomy; D007208:Indocyanine Green / Q000493:pharmacokinetics*; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000503:physiopathology; D008111:Liver Function Tests; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000410:Alanine Transaminase; D002802:Cholinesterases; D000469:Alkaline Phosphatase; D007208:Indocyanine Green; D001663:Bilirubin