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  • Endogenous production of carbon monoxide in normal and erythroblastotic newborn infants

    M. Jeffrey Maisels, … , David G. Nathan, Clement A. Smith

    J Clin Invest. 1971;50(1):1-8. https://doi.org/10.1172/JCI106463.

    The endogenous production of carbon monoxide (˙VCO) in newborn infants was measured by serial determinations of blood carboxyhemoglobin during rebreathing in a closed system. Mean ˙VCO in nine full-term infants was 13.7 ±3.6 µl CO/kg per hr (SD), and in four erythroblastotic infants ˙VCO ranged from 37 to 154 µl CO/kg per hr preceding exchange transfusion. Mean red cell life-span (MLS) and total bilirubin production were calculated from ˙VCO. MLS in normal newborns was 88 ±15 days (SD), and bilirubin production was 8.5 ±2.3 mg/kg per 24 hr. This is more than twice the amount of bilirubin normally produced in the adult per kilogram of body weight. Normal infants achieved a net excretion of bilirubin of at least 5.6 ±2.3 mg/kg per 24 hr (SD) as calculated from the bilirubin production and the measured rise in serum bilirubin concentration.

    The measurement of ˙VCO should prove valuable in the study of red blood cell survival and bilirubin metabolism in the newborn infant.

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  • Endogenous Production of Carbon Monoxide in

    Normal and Erythroblastotic Newborn Infants

    M. JEFREY MAIss, AMBADAs PATHAK, NiCHOLAs M. NELSON, DAvm G. NATHAN, and CLEMETr A. SMrm From the Laboratory for Neonatal Research, Boston Hospital for Women, Division of Hematology of the Children's Hospital Medical Center, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

    A B S T R A C T The endogenous production of carbon monoxide (Vco) in newborn infants was measured by serial determinations of blood carboxyhemoglobin dur- ing rebreathing in a closed system. Mean Vco in nine full-term infants was 13.7 zt3.6 Al CO/kg per hr (SD), and in four erythroblastotic infants Vco ranged from 37 to 154 sl CO/kg per hr preceding exchange trans- fusion. Mean red cell life-span (MLS) and total bili- rubin production were calculated from Yco. MLS in normal newborns was 88 :1:15 days (SD), and bilirubin production was 8.5 =12.3 mg/kg per 24 hr. This is more than twice the amount of bilirubin normally pro- duced in the adult per kilogram of body weight. Normal infants achieved a net excretion of bilirubin of at least 5.6 4-2.3 mg/kg per 24 hr (SD) as calculated from the bilirubin production and the measured rise in serum bilirubin concentration. The measurement of Vco should prove valuable in the

    study of red blood cell survival and bilirubin metabolism in the newborn infant.

    INTRODUCTION

    The recent studies of Coburn and coworkers (1-3) have confirmed the original observations by Sjbstrand (4-6) that carbon monoxide (CO) is endogenously pro- duced in normal man, and that approximately 1 mole of CO is produced per mole of heme catabolized (2).

    Interest in neonatal hemoglobin turnover has led previous investigators (7-10) to measure blood carboxy-

    Dr. Maisels' present address is the Department of Hema- tology, Walter Reed Army Institute of Research, Washing- ton, D. C. 20012. This work was presented in part at the Annual Meeting

    of the Society for Pediatric Research, Atlantic City, New Jersey, May 1969. Received for publication 2 January 1970 and in revised

    form 22 June 1970.

    hemoglobin (COHb)1 levels in normal newborn infants and in those with jaundice of hemolytic and non- hemolytic origin. In hemolytic disease of the newborn they demonstrated an elevated level of COHb which was assumed to be due to an increase in CO production (Vco) resulting from increased hemoglobin destruction. Although a correlation has, indeed, been shown to exist between blood COHb and Vco (11, 12) the relationship is too uncertain to derive an accurate indication of hemoglobin turnover from COHb (11). Wranne (13-15) and Fallstrbm (12, 16) have mea-

    sured the pulmonary excretion of CO in newborn infants. This measurement may not accurately reflect CO production because of the difficulty in achieving a steady state between Vco, the critical measurement, and the rate of CO excretion via the lung (11). We have adapted Coburn's rebreathing system for the

    measurement of Vco (1, 17) to the study of newborn infants. With this technique an alteration in CO pro- duction can be measured within minutes after it has occurred (18), and we have been able to calculate hemoglobin catabolism, red blood cell survival, and bilirubin production in the newborn infant.

    METHODS Rebreathing circuit The closed rebreathing circuit is shown in Fig. 1. The

    method of sealing the infant's face into the rebreathing mask is similar to that described by Cross (19).. The infant's face emerges through a pneumatic cuff2 (a) which seals against the face and the surrounding plastic ring (b) onto which a lid is sealed by spring clips. A stop cock (e) allows gas sampling and CO addition at the end of the procedure (see below). The blower (g) circulates air at approximately 15 liters/min. At

    I The terms COHb, COHb%, and COHb per cent saturation' are used interchangeably throughout this paper. All imply the per cent of hemoglobin saturated with carbon monoxide. 2Dunlop Company, Ltd., Manchester, England.

    The Journal of Clinical Investigation Volume 50 1971 I

  • this rate of flow through the CO2 absorbent (f) (650 ml of Baralyme),' less than 1% CO2 is detectable in the circuit. Humidified oxygen is added via a 50ml syringe at e in amounts sufficient to maintain a constant circuit volume. A thin walled rubber tube, 36 cm long and 6 cm in diameter,

    is sealed inside a solid plastic tube (c) as illustrated. Rubber stoppers at either end have an outlet for the circulating gas and an additional inlet at one end for oxygen (e). This device allows the addition of oxygen when required without the use of a rubber bag (1) which could act as "dead space" and pre- vent complete circulation of CO throughout the sytem. A Krogh spirometer (d) is connected to an outlet from the plastic tube and reflects volume changes occurring in the circuit. The use of the spirometer outside of the circuit allows the volume of the system to be kept as small as possible (about 2 liters).

    Conduct of study The infant was placed in the system, and the oxygen tension

    was adjusted to approximately 150 mm Hg. Thereafter, as oxygen was consumed by the infant, it was replaced so as to maintain circuit volume constant as measured by the spi- rometer. Oxygen tension was monitored frequently throughout the study4 and adjusted, if necessary, by the addition of extra oxygen. After rebreathing had continued for at least 15 min (1, 17, 20) the first blood sample was taken. Subsequent samples were taken at 30-min intervals for 1 hr. Blood was taken anaerobically either from an indwelling, size 21, scalp vein needle inserted into an antecubital vein, or from free flow- ing arterialized heel prick samples, the same method of sampling being used throughout a given study. 1 ml of blood was sufficient for duplicate analyses.

    Total time involved in the study including the initial equilibration, determination of the dilution factor (see below), insertion of an indwelling needle, and settling the baby into the system, was usually close to 3 hr, by which time most full-term infants were showing signs of restlessness, crying, and/or hunger. When these occurred, leaks' were apt to develop around the baby's face. At the end of the period of observation of the rate of increase of COHb, 0.92 ml (STPD) of 99.5% CO gas, was added to the system at e (Fig. 1), and a final blood sample was taken 45 min later. The maximum blood CO level measured after the addition of CO was 0.736 ml/100 ml or 3.48% of hemoglobin saturated with CO(1).

    Blood analysis The blood samples were analyzed for CO by liberating

    bound CO with acidified potassium ferricyanide and a hemo- lyzing agent (Triton X-100; Rohm and Haas Co., Phila- delphia, Pa.). The liberated blood gases were then extracted under vacuum using the modified microgasometer described by Natelson and Stellate (21) followed by injection into a gas chromatograph (Perkin-Elmer 154L). The method of gas in- jection was modified from Farhi, Edwards, and Homma (22) where the connecting tube leading from the upper two-way

    ' BaralymeR is obtainable from Warren E. Collins, Inc., Braintree, Mass 4IL 113 pH/gas analyzer PC2 electrode; Instrumentation

    Laboratory, Inc., Watertown, Mass. ' Leaks could be detected by a number of means, including

    rapid fall of the spirometer bell, and could be corrected by in- creasing the inflation of the pneumatic cuff seal or by wedging the infant's face into the cuff more firmly by means of an in- flatable pillow.

    6 CO 99.5%; Matheson Co., Inc., East Rutherford, N. J.

    02 source

    jh

    FIGuRE 1 Rebreathing circuit showing pneumatic cuff (a), plastic ring (b), plastic tube with thin-walled rubber tube (c), spirometer (d), stopcocks (e), CO2 absorbent (If), variable speed blower (g), and oxygen source.

    stopcock of the microgasometer is connected to two limbs of a four-arm, four-way stopcock. Blood samples of 0.24 ml were drawn up followed by reagents in the following order: 0.025 ml of 1 N lactic acid, 0.024 ml of 10% potassium ferricyanide, 0.1 ml of a solution containi