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Effects of hypoxia and acidity on the initiation of respiration
9 68
Society for Pediatric Research
43. Effects of bypoxla and acidity on the initiation of respiration Herbert S. Harned, Jr., William S. Berryhill, Jr., "~ Clarence A. Griffin, ~ and Loren
G. MacKinney, University of North Carolina School of Medicine, Chapel Hill, N. C. The effects of hypoxia and acidity on the initiation of respiration of term lambs were studied by two methods that discern chemoreceptor activation. (1) Perfusion of the right common carotid artery with blood with lower pO2, but similar pGO2 and p H to that in the fetal carotid artery invoked slow and erratic respirations after 15 sec. in 2 of 4 lambs and none in 2 other lambs. In contrast, perfusion of blood with lowered p H as well as low pO2 invoked more rapid and persistent respirations in all 5 additional lambs studied. (2) In another group of experiments, fetal carotid sinus nerve potentials were amplified for simultaneous oscillographic visualization, for broadcast by loud speaker, and for FM tape recording. The magnitude of chemoreceptor activity was determined, during ventrlcular diastole to preclude baroreceptor activity, by integrating and summating the recorded wave forms. The degree of chemoreceptor activity, as determined during basal fetal conditions, during administration of hypoxic and hypoxic-hypercarblc gas mixtures to the ewes, and after clamping of the umbilical cord was found to be proportional to the magnitude of the stimulus, such that after cord occlusion a marked increase in chemoreceptor activity was noted. The experiments show that increased H + ion concentration in carotid arterial blood potentiates the hypoxic stimulation of chemoreceptors and that a marked chemoreceptor discharge follows clamping of the umbilical cord. The results are compatible with a hypothesis that respirations are initiated in the newborn by a summation of neural stimuli, including an important traffic of chemoreceptor impulses, to the medullary respiratory centers.
44. Glycogen metabolism after prolonged hypoxia in newborn rabbits Uwe Stave, Fels Research Institute, Yellow Springs, Ohio On the first day of life rabbits were kept in an atmosphere of 6 per cent 02 and 5 per cent CO~ in N~ for 12 or 24 hours. At the end of this treatment they were anesthetized and some blood, liver, ventrieular muscle, and skeletal muscle were removed. Neither experimental nor control animals were fed after birth. The same experiments were carried out with adult rabbits (9 per cent 02 for hypoxia). The following metabolites will be dis-
November 1966 cussed: Glycogen in liver, heart, and skeletal muscle, lactate in blood and Iiver, pyruvate and glucose concentration in the blood. Results of the 24 hour hypoxia experiments: The liver glycogen concentration decreases i n newborns to 68 per cent of that of the controls and increases in adults to a level 16 times higher than that of the controls. The glycogen content of heart and skeletal muscle does not change in newborns, but for adults it is increased 167 per cent in the heart and is slightly lowered in the skeletal muscle. These changes in glycogen concentrations are accompanied by an 18 per cent decrease in blood glucose level in newborns and a 74 per cent increase in adults; the lactate concentration in blood and liver is increased to high levels in newborns (79 and 378 per cent, respectively) and to a lesser extent in adults (60 and 65 per cent). The blood pyruvate decreases in newborns and increases in adults. These results demonstrate an important difference between the glycogen metabolism of the newborn and the adult after prolonged exposure to hypoxia.
45. Energy substrates in the respiratory distress syndrome John Downes, ~" Lois Johnson, Subhash Arya, ~ and Thomas Boggs, Section on
Newborn Pediatrics, Pennsylvania Hospital, and the Departments of Pediatrics, and Anesthesiology of the School of Medicine, University of Pennsylvania, Philadelphia, Pa. Recent studies emphasize the importance of lipid metabolism in the human newborn (Novak, 1965). To determine the relationship of survival with mobilization of free fatty acids (FFA), 14 premature infants with moderate to severe idiopathic respiratory distress syndrome (RDS) had sequential umbilical artery acid-base, FFA , ketone, and glucose studies initiated at age 4 hours. All infants received oxygen, thermal control, intravenous glucose infusion, and intravenous NaHCO3 to correct the calculated base deficit. Five infants died, 4 by 30 hours of age. Seven normal newborns served as fasting controls. Mean arterial blood data (-+S.E.) at ages 4 to 18 hours for initial pH, peak FFA, peak ketone, and lowest glucose are shown in the accompanying tabulation. By age 18 hours, surviving infants with RDS receiving glucose have mobilized FFA to the same or greater extent than fasting control infants. Nonsurviving RDS infants have a lower peak FFA (p < 0.001) by the same age, a phenomenon observed in nonsurviving newborn lambs ( V a n Duyne, 1960). Ketone levels in su:rviving RDS infants were greater (p < 0.05) than in fasting control infants despite infusion of glucose, indicating that surviving infants with R D S must rely on fat stores as an energy source. T h e s e studies suggest
Society for Pediatric Research
43. Effects of bypoxla and acidity on the initiation of respiration Herbert S. Harned, Jr., William S. Berryhill, Jr., "~ Clarence A. Griffin, ~ and Loren
G. MacKinney, University of North Carolina School of Medicine, Chapel Hill, N. C. The effects of hypoxia and acidity on the initiation of respiration of term lambs were studied by two methods that discern chemoreceptor activation. (1) Perfusion of the right common carotid artery with blood with lower pO2, but similar pGO2 and p H to that in the fetal carotid artery invoked slow and erratic respirations after 15 sec. in 2 of 4 lambs and none in 2 other lambs. In contrast, perfusion of blood with lowered p H as well as low pO2 invoked more rapid and persistent respirations in all 5 additional lambs studied. (2) In another group of experiments, fetal carotid sinus nerve potentials were amplified for simultaneous oscillographic visualization, for broadcast by loud speaker, and for FM tape recording. The magnitude of chemoreceptor activity was determined, during ventrlcular diastole to preclude baroreceptor activity, by integrating and summating the recorded wave forms. The degree of chemoreceptor activity, as determined during basal fetal conditions, during administration of hypoxic and hypoxic-hypercarblc gas mixtures to the ewes, and after clamping of the umbilical cord was found to be proportional to the magnitude of the stimulus, such that after cord occlusion a marked increase in chemoreceptor activity was noted. The experiments show that increased H + ion concentration in carotid arterial blood potentiates the hypoxic stimulation of chemoreceptors and that a marked chemoreceptor discharge follows clamping of the umbilical cord. The results are compatible with a hypothesis that respirations are initiated in the newborn by a summation of neural stimuli, including an important traffic of chemoreceptor impulses, to the medullary respiratory centers.
44. Glycogen metabolism after prolonged hypoxia in newborn rabbits Uwe Stave, Fels Research Institute, Yellow Springs, Ohio On the first day of life rabbits were kept in an atmosphere of 6 per cent 02 and 5 per cent CO~ in N~ for 12 or 24 hours. At the end of this treatment they were anesthetized and some blood, liver, ventrieular muscle, and skeletal muscle were removed. Neither experimental nor control animals were fed after birth. The same experiments were carried out with adult rabbits (9 per cent 02 for hypoxia). The following metabolites will be dis-
November 1966 cussed: Glycogen in liver, heart, and skeletal muscle, lactate in blood and Iiver, pyruvate and glucose concentration in the blood. Results of the 24 hour hypoxia experiments: The liver glycogen concentration decreases i n newborns to 68 per cent of that of the controls and increases in adults to a level 16 times higher than that of the controls. The glycogen content of heart and skeletal muscle does not change in newborns, but for adults it is increased 167 per cent in the heart and is slightly lowered in the skeletal muscle. These changes in glycogen concentrations are accompanied by an 18 per cent decrease in blood glucose level in newborns and a 74 per cent increase in adults; the lactate concentration in blood and liver is increased to high levels in newborns (79 and 378 per cent, respectively) and to a lesser extent in adults (60 and 65 per cent). The blood pyruvate decreases in newborns and increases in adults. These results demonstrate an important difference between the glycogen metabolism of the newborn and the adult after prolonged exposure to hypoxia.
45. Energy substrates in the respiratory distress syndrome John Downes, ~" Lois Johnson, Subhash Arya, ~ and Thomas Boggs, Section on
Newborn Pediatrics, Pennsylvania Hospital, and the Departments of Pediatrics, and Anesthesiology of the School of Medicine, University of Pennsylvania, Philadelphia, Pa. Recent studies emphasize the importance of lipid metabolism in the human newborn (Novak, 1965). To determine the relationship of survival with mobilization of free fatty acids (FFA), 14 premature infants with moderate to severe idiopathic respiratory distress syndrome (RDS) had sequential umbilical artery acid-base, FFA , ketone, and glucose studies initiated at age 4 hours. All infants received oxygen, thermal control, intravenous glucose infusion, and intravenous NaHCO3 to correct the calculated base deficit. Five infants died, 4 by 30 hours of age. Seven normal newborns served as fasting controls. Mean arterial blood data (-+S.E.) at ages 4 to 18 hours for initial pH, peak FFA, peak ketone, and lowest glucose are shown in the accompanying tabulation. By age 18 hours, surviving infants with RDS receiving glucose have mobilized FFA to the same or greater extent than fasting control infants. Nonsurviving RDS infants have a lower peak FFA (p < 0.001) by the same age, a phenomenon observed in nonsurviving newborn lambs ( V a n Duyne, 1960). Ketone levels in su:rviving RDS infants were greater (p < 0.05) than in fasting control infants despite infusion of glucose, indicating that surviving infants with R D S must rely on fat stores as an energy source. T h e s e studies suggest