Robert V. Kotas

Phototherapy for neonatal hyperbilirubinemia—a dose: response relationship

The relationship between irradiance (microwatts per square centimeter) from visible light in the blue spectral range and the serum bilirubin response was studied in 44 newborn infants with nonhemolytic hyperbilirubinemia. Patients were separated into study groups (1 to 4) on the basis of quantity of irradiance received. A significant positive correlation was noted in the decreases in the 24 hour serum bilirubin values and the amount of blue light irradiance received. The relationship is nearly linear. The importance of using a radiometer to measure light irradiance in microwatts per square centimeter per 420 to 470 nm. during phototherapy for neonatal hyperbilirubinemia is stressed.

The Significance of Circulating Glycerol as a Precursor of Pulmonary Phosphatidylcholine in the Developing Mammalian Lung

Extract: There is scant information regarding the contribution made by circulating precursors to pulmonary phosphatidylcholine synthesis in the developing mammalian lung. In situ pulmonary artery perfusions were performed in term New Zealand newborn rabbits with physiologic buffer containing either 3.6 mM or 10.8 mM glycerol. There was a twofold increase in nanomoles of glycerol-phosphatidylcholine synthesized at 30 min when the higher concentration of glycerol was used. Continuing with the higher concentration, a near three-fold increase was observed between the 30-min and 60-min perfusions. This data indicates that the de novo synthesis of pulmonary phosphatidylcholine is influenced by the concentration of glycerol in the perfusate as well as the duration of perfusion.Speculation: The observation that the concentration of circulating glycerol can influence the de novo synthesis of pulmonary phosphatidylcholine suggests that glycerol may also play a role in providing precursor for pulmonary surfactant synthesis. The biochemical similarity of lipid metabolism at birth between human newborn infants and the newborn rabbit encourages extrapolation of this data to humans. The question is raised as to the influence that intravenous glycerol at physiologic concentration would have on pulmonary phosphatidylcholine synthesis in the infant with hyaline membrane disease.

Glycerol as a Phosphatidyl Choline Precursor in the Developing Mammalian Lung

In vitro evidence demonstrates that glycerol is actively incorporated by the developing mammalian lung into phosphatidyl choline (PC synthesis) and such incorporation is a good indi

A New Model for Neonatal Pulmonary Hemorrhage Research

Extract: Hemorrhagic atelectasis was successfully produced in newborn rabbits by pharmacologically narrowing airways leading to alveoli ventilated with oxygen-enriched gas. Between 48% and 62% of alveoli filled with blood cells. Areas of lung with a tendency to collapse were measured by pressure volume studies. Animals given supplemental oxygen retained 56% of total lung volume compared with 79% in the pilocarpine group, which suggested increased effectiveness of antiatelectasis factors in the latter. Less total lung gas was present in the pilocarpine group (4.0 ± 0.4 cc/g) compared with oxygen controls (5.1 ± 0.81 cc/g), which indicated more noninflatable lung. Neither surfactant deficiency nor heart failure needed to be present for pulmonary hemorrhage to occur.Speculation: Neonates are at increased risk of pulmonary hemorrhagic atelectasis because of their incomplete pulmonary anatomic development, if their airways become obstructed while breathing high concentrations of oxygen.

FAILURE OF PRETREATMENT WITH WR-2721 TO PROTECT RABBIT LUNG FROM IRRADIATIATION DAMAGE

Radioprotective drugs such as S-2 [3-Aminopropylamino] Ethylphosphorothioic acid (WR-2721) have been suggested for use to prevent radiation pneumonitis complicating radiotherapy of primary and metastatic tumors of lung, mediastinum, and chest wall. Juvenile female New Zealand White rabbits (R) between 9 and 12 months of age were either given saline or WR-2721 (36.5 mg/Kg) intravenously 15 minutes before irradiation. Low dose R (n=7) received 250 rads × 4 days to the thorax while high dose R (n=7) were given 375 rads × 4 days. Two, four and six weeks after initiating irradiation, animals were killed and pulmonary pressure volume studies performed. No significant differences between treated or control R (n=7) were seen in body weight change, food intake, water consumption, respirations, PaCO2, WBC, Hct, rectal temp, lung weight, lung distensibility, lung compliance, minimal surface tension or histologic changes. Pretreatment with WR-2721 does not seem to protect juvenile rabbit lung from irradiation damage.

PYRUVATE DEHYDROGENASE IN PRETERM, TERM AND ADULT RABBIT TISSUES

Pyruvate dehydrogenase activity was determined in the livers (LV), kidneys (KD), hearts (H), lungs (LG) and brains (BR) of 28.5d. (preterm), 30.5d. (term) and adult rabbits as part of our investigations of neonatal oxidative metabolism.We found that in KD, H, LG and BR the sp. act. of this enzyme (nmoles CO2 liberated from [1-14C]pyruvate/mg mitochondrial protein per min) decreased with gestation, reaching adult levels in 30.5d. rabbits. In the liver, we found an approximate two-fold increase in the sp. act. from 28.5d. to 30.5d. rabbits (8.32 vs 14.20). In addition, the percentage of the enzyme in the active form in the 30.5d. rabbit was found to be 5 and 2.5 fold greater in the H and BR than in the H and BR of the 28.5d. rabbit.The activity of this enzyme was also determined in whole tissue homogenates. When total activities per gram of tissue (active + inactive) were compared, it was found that the livers of the 28.5d. and 30.5d. rabbits were capable of the most rapid rates of pyruvate oxidation of the tissues studied. This is quite different from the relationship of the activities of the various tissues in the adult. The order of the maximum possible rates of pyruvate oxidation per gram was found to be: LV>H>KD>BR>LG, LV>H>BR>KD>LG and H>KD>BR>LV>LG in 28.5, 30.5 and adult rabbits, respectively.

INHIBITION OF FETAL PULMONARY SURFACTANT APPEARANCE AFTER MATERNAL METYRAPONE INFUSION

Pulmonary maturity was measured in fetal rabbits after continuous infusion of metyrapone (M)(7 mg/ml at 2 ml/hr × 24 hrs) to 24 day gestation females and compared to placebo treated controls (C). 27.5 day gestation animals (total N = 56) were compared for body weight in gm (BW), wet lung weight expressed as % of body weight (LW%), mg DNA per lung (DNA), minimal surface tension of minced lung in dynes per cm (MST), distensibility expressed as cc per gm of wet lung at peak distending P of 35 cm H2O (cc/gm), and deflation stability expressed as % of maximal volume upon deflation to a P of 10 cm H20 (%Vmax). All results are mean ± standard deviation; * = p < .001.Decreased %Vmax and increased MST after M are similar to findings in 26 day gestation fetal rabbits (JAP 30:358, 1971). Two additional M litters delivered at term (31 days) and 15 out of 17 bunnies survived to one month of age. Previously reported (Amer. Rev. Resp. Dis. 107:1109, 1973) accelerated appearance of pulmonary surfactant after intermittent metyrapone (300 mg I.M. Q8HX12) may have been due to incomplete block of adrenal 11-β hydroxylation.