EDITORIAL SYNOPSIS Unconjugated bilirubin is believed to be toxic to the brain in neonates. Previous work in vitro has shown an important effect on depression of cell respiration and phosphorylation. The present study in vivo fails to confirm these findings in the liver. The exact mechanism of kernicterus remains uncertain.Studies in vitro of various tissues, including liver, have shown that unconjugated bilirubin at high concentrations uncouples phosphorylation from oxidation (Ernster, 1961). It has accordingly been postulated that the unconjugated bilirubin exerts its cytoxic effect in kemicteric brain (Ernster, 1961), and possibly in intensely hyperpignented liver (Brown, Grodsky, and Carbone, 1964;Rozdilsky, 1961) in vivo by interfering with the synthesis of adenosine triphosphate (ATP) which is essential for the proper metabolic function of these organs.The present study provides an assessment of the effect of high levels of unconjugated bilirubin in vivo on hepatic ATP concentration and respiration. The results of this investigation, apparently the first one in living animals, are the basis of this report.
MATERIALS AND METHODSEXPERIMENTAL PROCEDURE Non-fasted 1-and 2-day-old guinea-pigs lightly anaesthetized with ethyl ether were infused via the inferior vena cava with 1 ml. of a solution of unconjugated bilirubin (Eastman Kodak, Rochester, New York), in physiological saline (2-5 mg./ml.), freshly prepared as described previously (Schenker and Schmid, 1964). Control litter mates received either the pigmentfree carrier solution or were sham-injected. Sixty minutes later liver was obtained from both experimental and control animals for measurement of ATP concentration or oxygen consumption and plasma was obtained for determination of total and direct-reading bilirubin concentration.