Endotoxin, cellular function, and nutrient blood flow

E. F. Asher, R. N. Garrison, D. J. Ratcliffe and D. E. Fry

To study the effects of endotoxemia on hepatic mitochondrial function and nutrient blood flow, rats were given intraperitoneal Escherichia coli endotoxin at a lethal dose for 90% mortality of group. Controls received only diluent. Five hours after the onset of endotoxemia, paired experimental and control animals had indocyanine green (ICG) clearance determined as the half-life (t1/2) at low (5 mg/kg) or high (15 mg/kg) doses. Low-dose ICG clearance represented hepatic nutrient blood flow; a Lineweaver-Burke plot of clearance rate v dose of administration provided extrapolation to an infinite dose and served as a sensitive indicator of hepatocellular function. Additional endotoxic rats were killed at five hours, liver and kidney mitochondria were isolated, and isolates were studied by the polarographic technique; the respiratory control index was determined as a sensitive indicator of efficient cellular oxygen metabolism with glutamate and succinate as substrates. Our data indicated that (1) uncoupling of the mitochondrial function is not identified during the early phase of endotoxemia, (2) reduced nutrient blood flow occurs during this early phase of endotoxemia, and (3) subsequent cellular abnormalities in endotoxemia may be secondary to ischemia and not direct cellular injury.