ABSTRACT. 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 (CCl 4 , 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. -KEY WORDS: CCl 4 , hepatectomy, hepatic functional mass, ICG Rmax, rat.J. Vet. Med. Sci. 59 (5): [335][336][337][338][339][340] 1997 serum biochemical compositions such as alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, albumin and cholinesterase (CHE) values in rats treated subcutaneously with carbon tetrachloride (CCl 4 ) for long terms.
MATERIALS AND METHODS
Animals:Male Sprague-Dawley (SD) rats aged 4 weeks were purchased from Japan S. L. C. (Hamamatsu, Japan), housed 2 or 3 per wire-mesh cage in an air-conditioned room and acclimated to the laboratory environment (temperature, 23 ± 2°C; humidity, 55 ± 15%; light cycle, 12 hr/day) for 1 to 3 weeks. They were given a commercial standard laboratory chow (F-2, Funabashi Farm, Japan) and tap water ad libitum. Before the experiments, the animals were fasted for at least 18 hr with free access to water, unless otherwise stated. All rats were treated humanely, and study protocols were in accordance with our institutional guideline for use of laboratory animals.Measurement of ICG Rmax: Six-week-old SD rats (165-195 g) were divided into five groups of 4 animals each to establish appropriate administration doses of ICG for the measurement of ICG Rmax. Five increasing doses (1.25, 2.5, 5, 10 and 20 mg/kg) of ICG were administered intravenously at an interval of 2 to 4 hr from the lowest dose into the right tail vein of the same rat by use of a 2.5-ml syringe attached to a 25-gauge needl...
