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Biomedical subjects

A R Laptook

Publications and source records attributed to A R Laptook.

At least 37 records · Page 2Linked to original sources
PubMed1995

Neurologic manifestations of in utero cocaine exposure in near-term and term infants.

OBJECTIVE: To determine whether the incidence of neurosonographic and neurologic abnormalities is higher in cocaine-exposed infants at birth. METHODS: In utero exposure to cocaine was investigated in 39 term and near-term infants with positive urine screens for cocaine only and 39 matched control infants without drug exposure admitted to the regular term newborn nursery. Serial evaluations were performed on each infant on postnatal days 1 and 2 and included a cranial sonogram, a neurologic and behavioral assessment for drug withdrawal, and Doppler interrogation of the anterior and middle cerebral arteries. RESULTS: There were no differences between groups in neurosonographic abnormalities. Grade I or II intraventricular hemorrhage occurred in 11% of cocaine-exposed and 11% of control infants. There were no cases of grade III intraventricular hemorrhage, cystic periventricular leukomalacia, or neonatal stroke. Head size was smaller in cocaine-exposed infants, ie, 32.7 +/- 0.1 cm versus 33.8 +/- 0.1 cm. The neurologic examination was similar between groups with regard to tone, reflexes, and cranial nerves. Behavioral scores were higher on both days, in cocaine-exposed versus control infants, ie, 4.4 +/- 0.5 versus 2.7 +/- 0.03 on day 1 and 5.0 +/- 0.5 versus 1.71 +/- 0.31 on day 2. Cerebral blood flow velocity measurements in the anterior cerebral artery were similar between groups on both days of examination. However, cocaine-exposed infants demonstrated a significant increase in flow velocity from day 1 to day 2, ie, 0.48 +/- 0.03 to 0.57 +/- 0.04. There was a concomitant decrease in the pulsatility index from day 1 to day 2 in the cocaine-exposed, ie, 0.74 +/- 0.02 to 0.69 +/- 0.02, but not in the control infants. No differences were noted in the flow velocities in the middle cerebral arteries between groups. CONCLUSIONS: Term and near-term infants admitted to a regular nursery who are exposed to cocaine in utero: (1) do not exhibit an increased incidence of neurosonographic abnormalities; (2) do exhibit altered behavior consistent with drug withdrawal; and (3) do demonstrate changes in flow velocity in the anterior cerebral artery consistent with the vasoconstrictive effects of the drug. However, these changes were not accompanied by changes in the neurologic examination or altered care. The long-term neurodevelopmental implications of these subtle abnormalities in the neonatal period remain to be determined.

Blood Flow Velocity↗
PubMed1994

The effects of systemic glucose concentration on brain metabolism following repeated brain ischemia.

Since systemic glucose concentration is an important determinant of ischemic brain metabolism in neonates, we sought to determine if the systemic glucose concentration influences brain metabolic alterations following repeated partial ischemia. A group of hyperglycemic piglets (n = 12) were compared to a group of modestly hypoglycemic piglets (n = 12) using in vivo 2H and 31P magnetic resonance spectroscopy to simultaneously measure cerebral blood flow and phosphorylated metabolites before, during and 30 min after two 10-min episodes of ischemia (i.e. Recovery 1 and 2). For both groups, beta-ATP levels at Recovery 1 and 2 were lower than Control (91 +/- 11 and 83 +/- 15% of Control, respectively for both groups combined, P = 0.002 vs Control). Inorganic phosphorus was elevated in hyperglycemic piglets at Recovery 1 and 2 (117 +/- 15 and 118 +/- 10% of Control). In contrast, in modestly hypoglycemic piglets inorganic phosphorus progressively rose from Recovery 1 (131 +/- 24% of Control) to Recovery 2 (149 +/- 37% of Control), and differed from the hyperglycemic group (P = 0.02). These changes did not correlate with post-ischemic cerebral blood flow, cerebral O2 delivery or cerebral glucose delivery. In both groups phosphocreatine and intracellular pH returned to Control values during Recovery 1 and 2. The progressive increase in inorganic phosphorus post-ischemia in hypoglycemic piglets suggests that modest hypoglycemia during and following repeated partial ischemia adversely affects immediate brain metabolic recovery.

Adenosine Triphosphate↗
PubMed1994

Age-related changes in swine brain creatine kinase-catalyzed 31P exchange measured in vivo using 31P NMR magnetization transfer.

31P exchange rates through the creatine kinase-catalyzed interconversion of phosphocreatine and gamma-ATP were measured in a total of 27 miniature swine ranging in age from 5 days preterm to 5 weeks old. A steep increase in the forward rate constant for 31P exchange from phosphocreatine (PCr) to gamma-ATP was observed between 2 days preterm and 3 days postterm, with a more gradual increase for older ages. In contrast, the [PCr]/[NTP] ratio measured by in vivo 31P nuclear magnetic resonance (NMR) remained constant throughout this age interval and close to unity. Forward and reverse rate constants and the rate of flux for 31P exchange were equal to each other for both preterm and 5-week-old animals, suggesting that the creatine kinase reaction is near-equilibrium for this span of age. Multifrequency steady-state saturation of P(i) and PCr compared to single-frequency saturation of PCr produced the same extent of saturation transfer to gamma-ATP, and the saturation of P(i) alone had no effect on the gamma-ATP 31P NMR signal. These results suggest that even for immature swine brain, creatine kinase activity should be adequate to buffer against changes in [ATP] when there is a mismatch between energy supply and energy demand, during conditions such as ischemia or hypoxia. The results from the present study indicate the unlikelihood that previously reported discrepancies between forward and reverse 32P flux rates in rat brain (Shoubridge et al., FEBS Lett 140:288-292, 1982) were due to neglect of gamma-ATP to P(i) exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Modest hypothermia provides partial neuroprotection for ischemic neonatal brain.

Hypothermia is a frequent occurrence in newborns, and thermoregulatory management is a fundamental part of medical stabilization. Although modest reduction in brain temperature (2-3 degrees C) before ischemia provides neuroprotection in adults, the effect of modest hypothermia on immature brain has not been examined. Nine-day-old swine were exposed to 15 min of incomplete global brain ischemia, with intraischemic rectal temperatures of either 38.3 +/- 0.4 degrees C (n = 10, normothermic) or 35.4 +/- 0.5 degrees C (n = 10, hypothermic). The relationship between rectal and brain temperature was delineated in preliminary experiments on four swine. Animals with intraischemic rectal temperatures maintained at either 39.5 degrees C or 35.5 degrees C were associated with a similar magnitude of difference in brain temperature. Therefore, rectal temperature was used to monitor brain temperature for 20 animals studied subsequently. Ischemia was induced by combining neck compression with hemorrhagic hypotension and resulted in similar group values for mean arterial pressure and changes in pH and blood gases at the completion of ischemia. A clinical overall performance score and brain tissue structure were evaluated after 72 h (or earlier if animals died prematurely). Hypothermic animals had less severe stages of impairment compared with the normothermic group (p = 0.023). Hypothermic piglets had less histologic damage in the neocortex at 0.5 cm beneath the brain surface (p = 0.048), the caudate nucleus (p = 0.038), and the pons/midbrain (p = 0.04) and the same direction of effect in neocortex at 1 cm beneath the surface (p = 0.07) and the cerebellum (p = 0.07) as compared with normothermic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Energy reserves and utilization rates in developing brain measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy.

Age-related changes in cerebral energy utilization were examined in swine, a species whose maximal rate of development is known to occur in the perinatal period. Interleaved in vivo 31P and 1H nuclear magnetic resonance spectroscopy was used to measure the rates of change in cerebral concentrations of phosphocreatine (PCr), nucleoside triphosphates, and lactate following complete ischemia, induced via cardiac arrest, in a total of 19 newborn, 10-day-old, and 1-month-old piglets. Preischemic concentrations of these three metabolites plus glucose and glycogen were determined in a separate experiment on 12 piglets whose brains were funnel-frozen in situ. The rate constants for the PCr and ATP decline and lactate increase were determined by nonlinear regression fits to the experimental data, assuming first-order kinetics. The rate constants and preischemic metabolite concentrations were used to calculate the initial flux of high-energy phosphate equivalents (approximately P), which was used as an estimate of cerebral energy utilization at the point when ischemia was initiated. Cerebral energy utilization equaled 6.5 +/- 1.9, 9.5 +/- 3.2, and 15.1 +/- 3.2 mumol approximately P/g/min in newborn, 10-day-old, and 1-month-old piglets, respectively. Within each age group the energy utilization rate was not altered by hyperglycemia-induced increases in cerebral energy reserves, but during hypoglycemia cerebral energy utilization rates decrease. The slope of approximately P versus time decreased with the duration of ischemia, indicating that cerebral energy utilization rates decrease after the first few minutes of ischemia. Newborn piglets had higher cerebral energy utilization rates compared with literature values for newborn rats and mice. This is consistent with the concept that newborns from a species with a perinatal stage of maximal growth and development will have higher cerebral energy demands compared with newborns from a species such as rodents, whose maximal growth occurs postnatally. However, this conclusion remains tentative because literature cerebral utilization rates estimated from the initial slope of approximately P-versus-time plots tend to underestimate the true rate, since the assumption of continued linearity may not be valid for the interval chosen.

Animals↗
PubMed1993

31P NMR relaxation does not affect the quantitation of changes in phosphocreatine, inorganic phosphate, and ATP measured in vivo during complete ischemia in swine brain.

Ischemia-induced changes in 31P NMR relaxation were examined in 16 piglets. NMR spectra were acquired under control conditions and during complete cerebral ischemia induced via cardiac arrest. Changes in T1 were assessed directly in six animals during control conditions and after 30-45 min of complete ischemia when changes in brain Pi levels had reached a plateau. The T1 for Pi did not change, i.e., 2.3 +/- 0.5 s during control conditions versus 2.4 +/- 1.0 s during ischemia. To evaluate phosphocreatine and ATP, two types of spectra, with a long (25-s) or short (1-s) interpulse delay time, were collected during the first 10 min of ischemia (n = 10). Both types of spectra showed the same time course of changes in phosphocreatine and ATP levels, implying that the T1 relaxation times do not change during ischemia. There were no changes in the linewidths of phosphocreatine, ATP, or Pi during ischemia, implying that the T2* values remain constant. Our results suggest that the 31P T1 and T2* for phosphocreatine, Pi, and ATP do not change during ischemia, and therefore changes in 31P NMR peak intensity accurately reflect changes in metabolite concentrations.

Adenosine Triphosphate↗
PubMed1993

The effect of hypercarbia on age-related changes in cerebral glucose transport and glucose-modulated agonal glycolytic rates.

This study examined the effect of hypercarbia on cerebral agonal glycolytic rates and brain lactate accumulation after complete ischemia induced by cardiac arrest. Before cardiac arrest, the blood plasma glucose concentration in seven newborn (113 d postconception; normal gestation, 115 d) and seven 1-mo-old (144 d postconception) piglets was adjusted to a specific value (range, 1 to 64 mM), and then inspired ventilation gases were changed to 10:50:40 CO2:O2:N2 for 20 min. The agonal glycolytic rate was measured by monitoring the rate of cerebral lactate formation in vivo using proton nuclear magnetic resonance spectroscopy, and postmortem brain lactate concentrations were measured biochemically in tissue extracts obtained 40 to 45 min after cardiac arrest. These data were compared with 21 normocarbic piglets of similar age, nine examined as part of the present study and 12 examined previously (Corbett RJT, Laptook AR, Ruley JI, Garcia D: Pediatr Res 30:579-586, 1991). There was a nonlinear relationship between the final postmortem brain lactate concentration and preischemia blood plasma glucose concentration that was most prominent in newborn piglets and previously had gone unnoticed. When analyzed using a steady-state model for glucose transport, this relationship revealed that normocarbic newborns had a lower preischemia affinity constant for the transport mechanism for glucose (2.8 +/- 1.5 mM) and lower cerebral glucose utilization rate relative to transport rate (0.12 +/- 0.04), compared with 1-mo-olds (4.5 +/- 1.4 mM and 0.30 +/- 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗
PubMed1992

Cerebral acid buffering capacity at different ages measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy.

Cerebral acidosis occurring during ischemia has been proposed as one determinant of tissue damage. Newborn animals appear to be less susceptible to ischemic tissue damage than adults. One possible component of ischemic tolerance could derive from maturational differences in the extent of acid production and buffering in newborns compared to adults. The purpose of this study was to measure the dependency of acid production on the blood plasma glucose concentrations and acid buffering capacity of piglets at different stages of development. Complete ischemia was induced in 29 piglets ranging in postconceptual age from 111 to 156 days (normal term conception, 115 days). Brain buffering capacity during the first 30 min of ischemia was quantified in vivo, via 31P and 1H nuclear magnetic resonance (NMR) spectroscopy, by measuring the change in intracellular brain pH for a given change in the concentration of compounds that contribute to the production of hydrogen ions. Animals from all four age groups showed a similar linear correlation between preischemia blood glucose concentration and intracellular pH after 30 min of ischemia. For each animal the slope of the plot of intracellular pH versus cerebral buffer base deficit was used to calculate the buffer capacity. Using data obtained over the entire 30 min of ischemia, there was no difference in the mean buffer capacity of the different age groups, nor was there a significant correlation between buffer capacity and age. However, there was a significant increase in buffer capacity for the intracellular pH range 6.6-6.0, compared to 7.0-6.6, for all age groups. No significant differences in buffer capacity for these two pH ranges were observed between any of the age groups. Acid buffering capacity was also measured by performing pH titrations on brain tissue homogenized in the presence of inhibitors of glycolysis and creatine kinase. Plots of homogenate pH versus buffer base deficit showed a nonlinear trend similar to that seen in vivo, indicating an increase in buffer capacity as intracellular pH decreases. A comparison of newborn and 1-month-old brain tissue frozen under control conditions or after 45 min of ischemia revealed no differences that could be attributed to age and a slight decrease in buffer capacity of ischemic brain compared to control brain tissue homogenates. There was no difference between the brain buffering capacity measured in vivo using 31P and 1H NMR and that measured in vitro using brain homogenates.

Acids↗
PubMed1992

Glucose-associated alterations in ischemic brain metabolism of neonatal piglets.

BACKGROUND AND PURPOSE: During global brain ischemia or hypoxia-ischemia in adults, hyperglycemia is deleterious to the brain. In contrast, similar adverse effects have not been found in neonatal animals. This investigation examined neonatal piglets to determine if there were specific alterations of ischemic brain metabolism associated with different systemic glucose concentrations and to potentially clarify the effects of hyperglycemia during ischemia in neonates. METHODS: Two groups of animals (n = 12 in each group) were studied during partial ischemia to compare the effects of hyperglycemia (plasma glucose concentration, 258 +/- 97 mg% [mean +/- SD]) with modest hypoglycemia (plasma glucose concentration, 62 +/- 23 mg%). A broad spectrum of cerebral blood flow reduction was achieved by combining inflation of a cervical pressure cuff with varying degrees of hemorrhagic hypotension. High-energy phosphorylated metabolites, intracellular pH, and cerebral blood flow were simultaneously measured using a magnetic resonance spectroscopic technique. Brain metabolic variables (beta-ATP, inorganic phosphorus, phosphocreatine, intracellular pH) were plotted as a function of blood flow reduction during partial ischemia for each group. RESULTS: During ischemia values of cerebral blood flow were comparably distributed between groups and ranged from 15% to 110% of those of control. At a given reduction of cerebral blood flow, hyperglycemic piglets maintained a higher concentration of beta-ATP (p = 0.011) and had a smaller increase in inorganic phosphorus (p less than 0.001). At cerebral blood flow less than 50% of control, the intracellular pH of piglets with modest hypoglycemia during partial ischemia was never reduced to less than 6.46, whereas intracellular pH fell as low as 5.97 for hyperglycemic animals. CONCLUSIONS: ATP preservation may account for the differing effects of glucose during ischemia in neonates compared with adults, provided that the accentuated brain acidosis is not deleterious to neonatal brain tissue.

Adenosine Triphosphate↗
PubMed1992

Blood flow and metabolism during and after repeated partial brain ischemia in neonatal piglets.

BACKGROUND AND PURPOSE: Our investigation sought to determine whether neonatal brain ischemic vascular and metabolic effects were altered by repeated episodes of ischemia. METHODS: We studied twelve piglets using in vivo magnetic resonance spectroscopy to obtain multiple, simultaneous measurements of cerebral blood flow and phosphorylated metabolites from the same tissue volume. The relationship between cerebral blood flow and energy metabolism was examined over a range of reduced cerebral blood flow (90-10% of control). Three episodes of partial ischemia were studied, each lasting 10 minutes and separated by 45 minutes. RESULTS: During each interval of ischemia, plots of the percent reduction in cerebral blood flow versus the percent change in phosphorylated metabolites (phosphocreatine, inorganic phosphorus) or unit change in intracellular pH did not differ in slope and intercept. The relationship between beta-ATP and cerebral blood flow during repeated ischemia revealed similar slopes, but a lower intercept during the third interval of ischemia (p = 0.029). After ischemia, cerebral blood flow was reduced as a function of the severity of the preceding ischemia. After each interval of ischemia, phosphocreatine and intracellular pH were unchanged from preischemic values. Inorganic phosphorus remained elevated after ischemia (117 +/- 16 and 118 +/- 11% of control, p less than 0.005, following the first and second intervals of ischemia), and beta-ATP was restored to progressively lower values (92 +/- 10 and 83 +/- 11% of control, p less than 0.025). Calculated free ADP decreased after ischemia and correlated with the postischemic level of beta-ATP (r = 0.63, p = 0.001). CONCLUSIONS: These results demonstrate that the relationship between cerebral blood flow and metabolism was reasonably preserved during repeated partial ischemia. However, following ischemia, alterations occurred in both cerebral blood flow and metabolism. These alterations may reflect a relative inhibition of ATP production by metabolic regulators such as ADP on either glycolysis or oxidative phosphorylation or both.

Adenosine Diphosphate↗
PubMed1991

Intraobserver and interobserver reliability in assessment of neonatal cranial ultrasounds.

Intraobserver and interobserver reliability in assessing neonatal cranial ultrasounds for periventricular-intraventricular hemorrhage (PVH-IVH) is not well studied; therefore, studies were designed to address this. For intraobserver reliability 180 cranial ultrasounds (360 hemispheres) were randomly selected from greater than 2000 ultrasounds and read twice by one radiologist in a blinded fashion. Ninety-eight percent were interpreted identically; of the 2% reinterpreted differently, all were initially abnormal but normal on the second reading. The least agreement occurred when interpreting ventricular size. Only four infants (1.1%) were placed in an unfavorable prognostic category (grades III and IV) on the first reading and a favorable prognostic category on the second interpretation (no bleed, grades I and II). To determine interobserver reliability, 20 sonograms were interpreted by eight independent observers representing five institutions. Using the multiple rater kappa kappa statistic, we determined interobserver agreement on overall impression (normal vs. abnormal), presence and extent of PVH-IVH (i.e. grade), presence of residual cyst, and ventricular dilatation. Greatest degree of agreement occurred when determining normal vs. abnormal, residual cyst, no bleed, and grades III and IV PVH-IVH. Poorest agreement occurred when reading grades I and II PVH-IVH and ventricular dilatation. After condensing interpretations of cranial ultrasounds into two prognostic categories, i.e. favorable (no bleed, grades I and II) and unfavorable (grades III and IV), there was excellent agreement among the observers.

Cerebral Hemorrhage↗
PubMed1991

Simultaneous measurement of cerebral blood flow and energy metabolites in piglets using deuterium and phosphorus nuclear magnetic resonance.

This report demonstrates the feasibility of using deuterium (2H) and phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy to make multiple simultaneous determinations of changes in cerebral blood flow, brain intracellular pH, and phosphorylated metabolites for individual animals. In vivo spectra were obtained from the brains of newborn piglets immediately following an intracarotid bolus injection of deuterium oxide. Experiments were performed at magnetic field strengths of 1.9 T (2H NMR only) or 4.7 T (interleaved 2H and 31P NMR). The rate of clearance of deuterium signal was used to calculate cerebral perfusion rates (CBFdeuterium) during a stable control physiologic state and conditions known to alter blood flow. CBFdeuterium values measured at 1.9 T under conditions of control (normocarbia, normotension), hypercarbia, hypocarbia, and varying degrees of ischemia induced by hypotension showed a significant positive correlation with values measured simultaneously using radiolabeled microspheres (CBFdeuterium = 0.4 x CBFmicrospheres + 8; r = 0.8). Simultaneous interleaved 2H and 31P NMR measurements under control conditions indicate that brain energy metabolites and intracellular pH remained at constant levels during the time course of the administration and clearance of deuterium oxide. Also, brain phosphorylated metabolites and intracellular pH did not differ significantly from their preinjection levels. Under control physiologic conditions, CBFdeuterium varied by +/- 6% and phosphorylated metabolite levels did not show a significant change with time, as measured from 15 blood flow determinations collected over 4 h. The results indicate that CBFdeuterium determinations have excellent reproducibility and do not affect brain energy metabolite levels. The procedures described here have the potential to bring a novel methodology to bear on investigating the relationship between cerebral perfusion and energy status during conditions such as ischemia or asphyxia.

Adenosine Triphosphate↗
PubMed1991

Effects of acute hypercapnia on maternal and fetal vasopressin and catecholamine release.

Although fetal asphyxia, i.e. hypoxemia, acidosis, and hypercapnia, increases plasma arginine vasopressin (AVP) greater than 40-fold, hypoxemia and metabolic acidosis occurring independently cause only 5-fold and 2-fold increases, respectively. To determine the effects of hypercapnia on AVP release, we examined the effects of acute hypercapnia on AVP secretion in six pregnant sheep and their fetuses at 135 +/- 4 d (chi +/- SD), exposing the ewe successively to room air, 30% O2, 30% O2 plus 10% CO2, 30% O2, and room air, and monitoring uterine blood flow, as well as maternal and fetal mean arterial pressure, heart rate, arterial blood gases, and plasma AVP and catecholamines. Oxygen exposure had no effect on the ewe or fetus. During O2 plus CO2 exposure, the ewes and fetuses developed hypercapnia in the absence of hypoxia, arterial CO2 tension increasing to 8.38 +/- 0.87 kPa (62.9 +/- 6.5 mm Hg) and 10.0 +/- 0.61 kPa (75.2 +/- 4.6 mm Hg) (p less than 0.001), respectively, at 30 min of exposure. Although fetal heart rate and mean arterial pressure were unchanged, maternal values rose 61 and 30% (p less than 0.001), respectively. At 30 min of O2 + CO2 exposure, maternal norepinephrine increased from 2.23 +/- 0.74 to 8.52 +/- 3.97 nmol/L (p = 0.15) and fetal epinephrine increased from 0.27 +/- 0.10 to 2.271 +/- 0.90 nmol/L (p = 0.01); plasma AVP was not significantly increased in the ewe or fetus, although levels rose from approximately 45 to 127 +/- 48 and 137 +/- 64 pmol/L (p = 0.10), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effect of age on glucose-modulated cerebral agonal glycolytic rates measured in vivo by 1H NMR spectroscopy.

The purpose of this study was to investigate the effect of plasma glucose concentration on cerebral agonal glycolytic rates in piglets of different ages. Twenty-four piglets were divided into four different age groups corresponding to 113, 121, 128, and 145 d postconception (normal gestation = 115 d). For each group the agonal glycolytic rate was measured by monitoring the rate of cerebral lactate accumulation after total ischemia. Ischemia was induced by cardiac arrest, and the rate of lactate formation was measured in vivo using proton nuclear magnetic resonance spectroscopy. Before cardiac arrest, the blood plasma glucose concentration for individual piglets was adjusted to a specific value in the range 1-30 mM. The dependence of agonal glycolytic rate upon blood glucose concentration was analyzed for each age group, using the Michaelis-Menten equation to evaluate Vmax, the maximal rate of glucose utilization, and Km the concentration of plasma glucose at which the half maximal rate of utilization occurs. Vmax for the two youngest age groups of piglets had significantly different (p less than 0.05) values compared with each other (1.38 +/- 0.17 and 1.92 +/- 0.64 mumol.g-1.min-1, respectively) and with the two older groups of animals (2.99 +/- 0.52 and 3.42 +/- 0.65 mumol.g-1.min-1, respectively). The Km values determined for the two youngest age groups (0.79 +/- 0.70 and 1.79 +/- 0.33 mM, respectively) also were significantly lower than for the two older age groups (4.96 +/- 2.90 and 4.82 +/- 2.96 mM, respectively). We conclude that throughout the first 2 wk of life there are marked increases in the cerebral glycolytic capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1990

Neonatal intracranial hemorrhage: I. Changing pattern in inborn low-birth-weight infants.

Many reports of the occurrence of periventricular-intraventricular hemorrhage (PVH-IVH) are biased by the inclusion of both inborn and outborn infants. To obviate this selection bias we examined a large inborn population of low-birth-weight infants to determine if the incidence of PVH-IVH changed over a 3-year interval from March, 1982 through February, 1985. Serial cranial ultrasonography was performed in 463 consecutive infants of birth weight less than or equal to 1500 g who survived for more than 8 h. The incidence of PVH-IVH decreased from 31.5% and 29.3% in years 1 and 2, respectively, to 23.7% in year 3 (P less than 0.05). The latter reflected a fall in the incidence of grades III and IV PVH-IVH, but no change in the incidence of grades I and II. This observation was not attributable to changes in mortality, the distribution of infants by birth weight and estimated gestational age in each year of the study, or infants excluded from the analysis. Contrary to most reports, 21.9% of all PVH-IVH during the 3 years were first diagnosed after 14 days postnatal age and were predominantly grade I. These results document not only a change in the epidemiology of PVH-IVH in an inborn population, but also the importance of serial cranial ultrasonography beyond the first week of life.

Birth Weight↗
PubMed1990

Neonatal intracranial hemorrhage: II. Risk factor analysis in an inborn population.

The ability to predict the occurrence of neonatal periventricular-intraventricular hemorrhage (PVH-IVH) would be useful in the design of clinical trials to prevent its occurrence. Therefore, data were collected from 463 consecutive infants less than or equal to 1500 g birth weight delivered between March 1, 1982 and February 28, 1985. This large population made it feasible to divide the infants into two groups, using one group to develop a model predictive of ICH and the second group to test the validity of the model. Infants were randomly grouped by sex, race, gestational age, birth weight, month of birth, mortality, and incidence and grade of worst PVH-IVH. In Group A (n = 232), respiratory distress syndrome, ventilator therapy, PaCO2 greater than or equal to 60 mmHg, PO2 less than or equal to 40 mmHg greater than or equal to 2 h, lower 1- and 5-min Apgar scores, lower pediatric estimation of gestational age, and pneumothorax were significantly associated with PVH-IVH by univariant analyses (chi 2, P less than 0.03). Multivariant discriminant analysis performed on Group A revealed that pneumothorax, cesarean section, PaCO2, and ventilator therapy were most predictive of PVH-IVH, but sensitivity was 55% and specificity 78%. Applying the model to Group B, sensitivity decreased to 21% while specificity rose to 93%. Logistic regression, which takes into account non-normally distributed variables, did not improve predictability.(ABSTRACT TRUNCATED AT 250 WORDS)

Apgar Score↗
PubMed1990

Acid homeostasis following partial ischemia in neonatal brain measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy.

The purpose of this study was to investigate neonatal brain energy metabolism, acid, and lactate homeostasis in the period immediately following partial ischemia. Changes in brain buffering capacity were quantified by measuring mean intracellular brain pH, calculated from the chemical shift of Pi, in response to identical episodes of hypercarbia before and after ischemia. In addition, the relationship between brain buffer base deficit and intracellular pH was compared during and following ischemia. Thus, in vivo 31P and 1H nuclear magnetic resonance spectra were obtained from the brains of seven newborn piglets exposed to sequential episodes of hypercarbia, partial ischemia, and a second episode of hypercarbia in the postischemic recovery period. For the first episode of hypercarbia, brain buffering was similar to values reported for adult animals of other species (percentage pH regulation = 54 +/- 16%). During ischemia, the brain base deficit per unit change in pH was -19 +/- 5 mM/pH unit, which is similar to values reported for adult rats. By 20-35 min postischemia, brain acidosis partly resolved in spite of a net increase in lactate concentration. Therefore, the consumption of lactate could not explain acid homeostasis in the first 35 min following ischemia. We conclude that H+/HCO3- or other proton equivalent translocation mechanisms must be sufficiently developed in piglet brain to support acid regulation. This is surprising, because a substantial body of evidence implies these processes would be less active in immature brain. The second episode of hypercarbia, from 35 to 65 min postischemia, resulted in a smaller decrease in brain pH compared with the first episode, a result indicating an increase in brain buffering capacity (percentage pH regulation = 79 +/- 29%). This was associated with a parallel decrease in brain lactate content, and therefore acid regulation could be attributed to either continued ion translocation or the consumption of lactate. A mild decrease in brain pH and content of energy metabolites was observed, a finding suggesting that the metabolic consequences of severe postischemic hypercarbia are neither particularly dangerous or beneficial.

Acidosis, Respiratory↗