Sn-protoporphyrin blocks the increase in serum bilirubin levels that develops postnatally in homozygous Gunn rats.

Administration of Sn-protoporphyrin to Gunn rats that are characterized by a genetically determined absence of UDP-glucuronyl transferase activity for bilirubin, 24-30 h after birth, prevented the marked increase in serum bilirubin concentration that occurs in these animals in the postnatal period. A second administration of Sn-protoporphyrin at day 6 maintained serum bilirubin levels in the neonates at the initial level for an additional 6 d. In contrast, in untreated Gunn neonates, serum bilirubin levels increased substantially as expected during the immediate 2-wk period after birth. Studies in adult Gunn rats demonstrated that Sn-protoporphyrin administration diminished biliary bilirubin output, decreased tissue heme oxygenase activity, and did not alter hepatic cytochrome P450 levels. These findings raise the possibility that Sn-protoporphyrin may prove clinically useful in maintaining low levels of serum bilirubin in congenitally jaundiced individuals, such as patients with the Crigler-Najjar syndrome.

Photodegradation of riboflavin in neonates.

The biologically most important flavins are riboflavin and its related nucleotides, all highly sensitive to light. It is because of its photoreactivity and its presence in almost all body fluids and tissues that riboflavin assumes importance in phototherapy of neonatal jaundice. The absorption maxima of both bilirubin and riboflavin in the body are nearly identical: 445-450 (447) nm. In consequence, blue visible light will cause photoisomerization of bilirubin accompanied by photodegradation of riboflavin. This results in diminished erythrocyte glutathione reductase, which indicates generalized tissue riboflavin deficiency and red cell lysis. Single- and double-strand breaks in intracellular DNA have occurred with phototherapy. This light exposure of neonates may result also in alterations of bilirubin-albumin binding in the presence of both riboflavin and theophylline (the latter frequently given to prevent neonatal apnea). Many newborns, especially if premature, have low stores of riboflavin at birth. The absorptive capacity of premature infants for enteral riboflavin is likewise reduced. Consequently, inherently low stores and low intake of riboflavin plus phototherapy for neonatal jaundice will cause a deficiency of riboflavin at a critical period for the newborn. Supplementation to those infants most likely to develop riboflavin deficiency is useful, but dosage, time, and mode of administration to infants undergoing phototherapy must be carefully adjusted to avoid unwanted side effects.

Transcutaneous bilirubinometry. III. Dermal bilirubin kinetics under green and blue light phototherapy.

Using the transcutaneous bilirubinometer, we studied the response of cutaneous bilirubin to different colors of light during phototherapy. Three groups of ten infants were exposed to blue, green, and blue-green lights at a mean postnatal age ranging from 50 to 77 hours. Patched areas served as controls. Every 15 minutes during four hours of phototherapy, we obtained simultaneous measurements from exposed and covered areas. After the onset of phototherapy, transcutaneous bilirubinometer values from the covered areas in all groups remained stable. The overall rate of bleaching was lowest in the green light group and highest in the blue-green combination group. In this group of infants, green light appeared to enhance the effectiveness of blue light in reducing dermal bilirubin concentrations as measured by the transcutaneous bilirubinometer.

Measurements and monitoring of phototherapy in newborn jaundice.

Hyperbilirubinemia in the newborn (neonatal jaundice) may cause irreversible brain damage if plasma concentrations of bilirubin exceed the number of binding sites on albumin and other blood components. Phototherapy or exchange transfusions to prevent the excessive rise in concentration of the pigment should be instituted in appropriate clinical situations. In phototherapy, the jaundiced infant is exposed to visible light containing the wavelength (about 450 nm) bilirubin will absorb. Because bilirubin is quite photolabile and will readily isomerize in vivo, it is rapidly converted to excretable forms. The effectiveness of this therapy, however, depends upon the maintenance of adequate radiant flux in the required wavelength. Energy output and spectral distributions of phototherapy lamps must be measured. The long-term effects of irradiation of newborn infants over several days are not yet known.

Molecular basis of hyperbilirubinemia and phototherapy.

Hyperbilirubinemia in the newborn results not only in visible yellow discoloration of the skin but, in high concentration, may cause bilirubin encephalopathy. Such damage to the central nervous system may be subtle and not apparent for several years, as with visual-motor perceptive defects; or it may cause severe neurologic damage (Kernicterus)--even death. Sick and immature infants are the most vulnerable to bilirubin toxicity. Although this condition affects nearly half of all newborns to some degree, only about 10% require treatment. Two methods of treatment are really effective in correcting hyperbilirubinemia, exchange blood transfusions, and/or phototherapy with light radiation in the blue part of the visible spectrum. If the rate of production of bilirubin is excessive or an infant's capacity to conjugate and excrete the pigment is deficient, bilirubin will accumulate in plasma, and will be taken up by other lipid-containing tissues, collagen, and (unless firmly bound to albumin) brain tissue. Many factors combine to raise plasma levels of bilirubin to toxic levels; for example, acidosis, sepsis, hypoxia, hemolysis, hypoalbuminemia, and certain competitive albumin binders. Bilirubin is photolabile in vivo, and if the whole body is irradiated with visible light in the absorption band (450-490 nm) of bilirubin, the pigment will undergo photocatabolism. Under phototherapy bilirubin undergoes photoisomerization at the meso double-bond to conformations less lipophyllic. It is now known that the major photo products of bilirubin IX-alpha are an unresolved mixture of its E, Z and Z, E isomers, easily excreted by the liver. Thus, phototherapy will reduce the accumulation of bilirubin in skin and other tissues and in circulating plasma.

Effect of broad and narrow spectrum fluorescent light on blood constituents.

Riboflavin in whole blood, G-6-PD activity in erythrocytes and amino acids in plasma of infants irradiated by broad and narrow spectrum blue fluorescent light were determined. Riboflavin was reduced by both types of light. Loss of G-6-PD activity during phototherapy with subsequent hemolysis was observed in some infants under each type of light source, both in vivo and in vitro. This phenomenon may be related to the indirect effect of riboflavin reduction and not to a direct effect upon the enzyme. The reduction of the plasma concentration of some amino acids observed under broad spectrum irradiation but not under pure blue light may not be of significance, but is of concern. These data indicate that all fluorescent light sources in current use for phototherapy produce biologic effects of importance beside the primary purpose of the treatment to reduce hyperbilirubinemia. It is apparent from the results of these studies that phototherapy light penetrates more deeply than the superficial skin to exert photochemical effects.