K. Schultz

Hyperaminoacidemia due to the accumulation of gluconeogenic amino acid precursors in hypoglycemic small-for-gestational age infants

The postnatal (3 to 12 hours) plasma amino acid patterns of normal full-term, nonhypoglycemic, and hypoglycemic small-for-gestational age infants were compared. Seventeen amino acid were separated by automatic column chromatography. It was found that hypoglycemia in SGA newborn infants was associated with a marked increase in total serum amino acid concentrations. This hyperaminoacidemia, which was mainly due to the increase in concentrations of alanine, glycine, proline, and valine, apparently reflected a decreased heapatic gluconeogenic capacity. A significant inverse correlation was observed between concentration of blood glucose and the accumulation of gluconeogenic amino acids. The proportionate accumulation of alanine, glycine, proline, and valine suggests a closely interrelated production and release of these amino acids from the peripheral pools. It is concluded that the changes in concentrations of plasma amino acids occurring in hypoglycemic SGA infants can be helpful in understanding the relative contribution of individual amino acids to gluconeogenesis in the human infant.

Comparative glycemic responses to alanine in normal term and small-for-gestational-age infants

The response of blood glucose to intravenously injected alanine (0.125 gm/kg) was examined in small-for-gestational-ageinfants and normal term infants within 24 hours after birth. The blood glucose concentration increased significantly in the normal infants, whereas in the malnourished infants there was only a slight increase. It was concluded that the significant difference in blood glucose increments, in response to alanine probably reflects the difference in the gluconeogenic capacity between the two groups of newborn infants.

Metabolic Responses to Severe Perinatal Asphyxia in Term Newborn Infants with Particular Reference to the Changes in Plasma Free Amino Acids

Blood glucose, blood lactate, plasma FFA, plasma alpha-amino nitrogen and 17 individual amino acids were determined on admission, and at 24 and 48 h after admission in severely asphyxiated term newborn infants. The blood glucose value was widely scatterred and the plasma FFA level was low on admission. The total free plasma amino acid content correlated closely with the severity of asphyxia-induced lactic acidosis. Among the 17 amino acids determined, 11 turned out to be significantly increased. The increase of plasma free amino acids might be toxic for the central nervous system, therefore parenteral feeding of asphyxiated neonates with amino acid mixtures can be dangerous.

Plasma and Cerebrospinal Fluid Hyperinsulinism in Asphyxiated Piglets

Insulin (I) plays a crucial role in the maturation of the perinatal brain, and it may also be involved in the pathogenesis of neonatal brain injuries. The aim of the present study was to reveal the effect of neonatal asphyxia on the regulation of I and glucose (G) metabolism in plasma and cerebrospinal fluid (CSF) in newborn piglets. The I concentrations were measured by radioimmunoassay, while the G levels were analyzed by the G oxidase method during three phases (basal, critical, recovery) of bilateral pneumothorax in newborn piglets. We observed a significant hyperinsulinism (p < 0.001) both in plasma and CSF and a mild hypoglycemia (p < 0.05) during the recovery period. Postasphyxial G infusion (1.1 M, 10 ml.kg-1) amplified the hyperinsulinism. The ICSF/plasma ratio (mean +/- SEM; n = 16) was decreasing during cardiovascular failure (0.09 +/- 0.02; NS) as compared with the initial value (0.12 +/- 0.04), then it returned to basal values by 60 min (0.14 +/- 0.04; NS), and increased significantly 180 min (0.40 +/- 0.14; p < 0.05) after resuscitation of the piglets. There was a similar increase in GCSF/plasma ratio in asphyxiated animals at the end of experiments (0.99 +/- 0.15 vs. initial 0.76 +/- 0.05; p < 0.05). In conclusion, neonatal asphyxia resulted in plasma and CSF hyperinsulinism which may alter hypoxic-ischemic cerebral damages.

PLASMA |[lpar]|P|[rpar]| AND CEREBROSPINAL FLUID |[lpar]|CSF|[rpar]| INSULIN |[lpar]|I|[rpar]| CONCENTRATION IS ELEVATED IN PIGLETS WITH EXPERIMENTAL NEONATAL PNEUMOTHORAX |[lpar]|PTX|[rpar]|

There is a lack of data on the level of I in P and CSF during neonatal cardiovascular collapse. Moreover, disturbances in glucose (G) homeostasis influences brain metabolism profoundly. Therefore, we have studied 10 newborn piglets (Group 1) during the course of PTX moasuring I by a RIA method and G concentrations in P and CSF, Stages of the disease were baseline; critical phase 65.0 ± 3.4 min after the beginning of the Induction of PTX (MABP:16.8 ± 05 mmHg; HR; 64.7 ± 1 4 min−1, pH: 6.89 ± 0.04, pO: 26.0 ± 2.0 mmHg). when animals were given 10 ml × b.w.kg−1 4.2 % v:v NaHCO1 /v Infusion and recovery (samples wore taken 0, 120 and 240 mm after the beginning of PTX and In critical phase). Data were compared to results taken from sham operated animals without PTX (Group 2. n=9. sampling at 0. 60, 120 and 240 min); all values are moans ± SEM). *p < 0.05 compared to values in Group 2.Conclusion: A significant hypoglycemia dovolops with a concomitant elevation of insulin levels in P and CSF in plglets with oxporlmontal PTX.

PLASMA (P) AND CEREBROSPINAL FLUID (CSF) INSULIN (I) CONCENTRATION IS ELEVATED IN PIGLETS WITH EXPERIMENTAL NEONATAL PNEUMOTHORAX (PTX)

There is a lack of data on the level of I in P and CSF during neonatal cardiovascular collapse. Moreover, disturbances in glucose (G) homeostasis influences brain metabolism profoundly Therefore, we have studied 10 newborn piglets (Group 1) during the course of PTX measuring I by a RIA method and G concentrations In P and CSF. Stages ol the disease were baseline; critical phase 65.0 ± 3.4 min after the beginning of the induction of PTX (MABP: 16.8 ± 05 mmHg; HR: 54.7 ± 1.4 min−1. pH: 6.89 ± 0.04, pO: 25.0 ± 2.0 mmHg), when animals were given 10 ml x b.w.kg−1 4.2 %v:v NaHCO3 /V infusion and recovery (samples were taken 0, 120 and 240 min after the beginning of PTX and in critical phase). Data were compared to results taken from sham operated animals without PTX (Group 2, n=9, sampling at 0, 60, 120 and 240 min); all values are means ± SEM), *p < 0.05 compared to values in Group 2Conclusion: A significant hypoglycemia develops with a concomitant elevation of insulin levels in P and CSF in piglets with experimental PTX.

228 POSTASPHYXIAL GLUCOSE ADMINISTRATION AGGRAVATES HYPER-INSULENISM IN PIGLETS WITH BILATERAL PNEUMOTHORAX

Insulin plays a role as a growth factor in the neuronal maturation and it may also have an influence on hypoxic-ischemic brain injuries in newborns. Clinical studies indicated, that hyperinsulinemia with hypoglycemia developed in asphyxiated neonates. Recently, we have also found a severe cerebrospinal fluid (CSF) hyperinsulinism during neonatal asphyxia in piglet. In the present study, we investigated the effect of postasphyxial glucose administration on the insulin levels measured by RIA in the plasma and CSF in newborn pigs. Bilatenl pneumothorax (PTX) was induced in 16 piglets; stages of the disease were baseline (B), critical (C) phase with cardiovascular and metabolic failure (arterial hypotension, bradycardia, hypoxemia, combined acidosis), and a 180-min recovery (R) after cardiopulmonary an I metabolic (i.v. infusion of NaHCO3 for 15 min, 0.5 mM/I, 10 ml/kg b.w.) resuscitation. 6 piglets (group 1) were also given i.v. glucose infusion (1.1 M/I) in the same final volume (10 ml/kg), while the remaining 10 animals (group 2) received no glucose. Insulin level wss increased in C phase compared to that in B in plasma (1018 ± 231 pM/I vs. 438 ± 81 pM/, n=16, p< 0.001, all values are means ± SEM), but it was unchanged in CSF (38 ± 5 pM/I vs., 42 ± 7 pM/I, n= 16, N.S.). A more severe hyperinsulinemia occurred in group 1 than in group 2 during R (3157 ± 738 pM/I vs. 1358 ± 495 pM/I, p<0.001 at 60-min-R; and 2211 ± 442 pM/l vs. 534 ± 245 pM/I, p<0.001, at 180-min-R). CSF hyperinsulinism was also significantly (p < 0.001) increased in group I compared to that in group 2 during R (239 ± 77 pM/l vs. 60 ± 13 pM/l, at 60-min-R; and 249 ± 52 pM/l vs. 164 ± 52 pM/l, at 180-min-R). In conclusion, glucose administration increased the asphyxia-induced hyperinsulinism in plasma and CSF of piglets, which may alter the severity of neonatal hypoxic-ischemic brain injuries.

117: Changes in blood glucose and plasma amino acids in response to glucagon infusion in small for gestational age infants

The study was designed to show the changes in plasma amino acids in relation the response of blood glucose to glucagon infusion / 0.2 ug/kg/min for 4 hrs /in 7 non-hypoglycaemic /NHSGA/ and 7 hypoglycaemic /HSGA/ newborn infants. In the NHSGA group blood glucose increased from 66±12 mg% to 136±16 mg % by 120 minutes, and thereafter it declined rapidly. In HSGA infants it rose from 22-2 mffH to 69-13 mg % which was maintained during the test period. The unopposed glycaemic action of glucagon suggested a difference in the interaction of hormones between the two groups of neonates. This dirference was also indicated by the observation, that while in the NHSGA group a progressive and significant decline occured in the mejority of amino acids, in the HSGA infants neither the glucogenic, nor the branched chain amino acids were significantly affected by glucagon. This unresponsiveness raises the guestion whether the sustained rise in blood glucose entirely resulted from glycogenolysis, or it could also attributed to stimulated gluconeogenesis, It is not unrealistic to suppose that under the metabolic conditions associated with hypoglycaemia hepatic uptake and intrahepatic disposition of accumulated amino acids, for a period of few hrs,may not necessarily respond simultaneously to glucagon.