THE ONSET OF SODIUM RETENTION IN EXPERIMENTAL CIRRHOSIS IN RATS IS RELATED TO A CRITICAL THRESHOLD OF LIVER-FUNCTION

Although sodium retention is a common coplication in advanced liver disease, the relationship between liver and kidney function in cirrhosis has not been well established. The objective of this study was to investigate this relationship in an experimental model of cirrhosis induced in phenobarbital‐treated rats by weekly intragatric adminstration of carbon terachloride. Liver function, measured by the aminopyrine breath test, and urinary sodium excretion on a constant salt diet, were measured weekly. Administation of carbon tetrachloride led to cirrhosis, sodium retention, ascites and a reduction in liver function as measured by the amino pyrine breath test in all 15 rats surviving the first 8 wk. The time to develop sodium retention (defined as a decridese in urinary sodium excretion rate to less than 0.3 mmol/24 hr) varied from 9 to 19 wk. The aminopyrine breath test rate constant of elimination was reduced from 24 × 10−3 min −2 2 × 10−3 at the start of carbon tetrachloride administration by 61% ± 10% at the time sodium retention occurrred. A linear decrease was seen in aminopyrine breath test rate constant of elimination in the weeks preceding the onset of sodium retention. Sodium retention occurred when aminopyrine breath test rate contant of elimination was reduced to a critical threshold of 10 × 10−3 ± 1 × 10−3 min−1, and then permitted to recover above this level by withdrawal of carbon tetrachloride. Sodium retention occurred when the aminopyrine breath test rate constant of elimination fell below the threshold; this was followed by spontaneous diuresis when aminopyrine breath test rate constant of elimnation in the weeks preceding the onset of sodium retention. Sodium retention occurred when aminopyrine breath test rate contant of elimination was reduced to a critical threshold of 10 × 10−3 ± 1 × 10−3 min−1, and then permitted to recover above this level by withdrawal of carbon tetrachloride. Sodium retention occurred when the aminopyrine breath test rate constant of elimination fell below the treshold: this was followed by spontaneous diuresiss when aminopyrine breath test rate constant of elimination improved above 10 × 10−3 ± 1 × 10−3 min−1. the onset of sodium retention preceded the onset of ascites in all rats. Theses results indicate a critical threshold of hepatic function in the phenobarbital, carbon terachloride model of cirrhosis, below which sodium retention followed by ascites formation occurs.(HEPATOLOGY 1990; 11:779‐786.) Copyright © 1990 American Association for the Study of Liver Diseases