Publications by authors named "Laptook A"

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.

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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.

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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.

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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.

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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.

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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.

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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.

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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).

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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We used neonatal piglets to determine the influence of plasma glucose concentration on cerebral energy metabolism during and immediately after partial ischemia. We assessed cerebral metabolism using in vivo phosphorus-31 magnetic resonance spectroscopy. Arterial plasma glucose concentration was increased in four piglets by systemic infusions of dextrose in water for comparison with infusions of saline in four controls or decreased in eight piglets by fasting for 24-48 hours for comparison with four fed piglets.

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We investigated postasphyxial brain damage with 31P magnetic resonance spectroscopy (MRS) and correlated it with neurologic assessment and standard laboratory evaluation during the first 10 months of life in 1 infant, baby G. We compared these observations to 31P MRS data from 7 healthy term newborns, 1 normal infant examined serially over the first 8.5 months of life, and 5 other term infants following perinatal asphyxia.

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Sequential 31P and 1H nuclear magnetic resonance spectra were measured for neonatal piglets (n = 7) to determine the relationship between brain intracellular pH (pHi), lactate, and phosphorylated energy metabolites during partial ischemia. Simultaneous determinations of arterial and cerebral venous blood gases, pH, O2 content, and plasma concentrations of glucose and lactate were also made. Ischemia, induced by bilateral carotid artery ligation plus hemorrhagic hypotension for 35 min, resulted in variable reductions in ATP, phosphocreatine, and increases in Pi, H+, and lactate relative to control levels.

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To determine the effects of lactic acidemia versus lactate on CBF, we infused lactic acid, either buffered with NaOH (L + NaOH) or with added NaCl (L + NaCl), to attain similar osmolalities in 18 piglets. CBF (microsphere technique), pH, blood gases, plasma osmolality, and cerebral arteriovenous differences of O2 content and lactic acid concentrations were measured prior to, at 30 min of a lactic acid infusion, and 15 and 90 min after completion of the infusion. Control arterial pH was comparable between groups (7.

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To determine if cerebral blood flow (CBF) and cerebral metabolic alterations during partial ischemia are affected by a prior interval of ischemia, 13 neonatal piglets were studied during two successive protocols (termed A and B), each consisting of an interval before, during and after partial ischemia induced by hypotension. Piglets were studied with either microspheres (n = 6) to measure CBF and calculate cerebral uptake of O2 and glucose or 31P nuclear magnetic resonance spectroscopy (n = 6) to measure intracellular pH (pHi) and cerebral phosphorylated metabolites. One piglet was used to determine time effects.

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In the fetus, arginine vasopressin (AVP) has been considered a "stress" hormone with primarily cardiovascular effects. In adult animals, AVP also has substantial endocrine effects, e.g.

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Ventilated piglets were studied before, during (15 min), and after (90 min) hemorrhagic hypotension to correlate a 60% reduction in cerebral blood flow with cerebral energy state using radiolabeled microspheres (n = 12) and in vivo 31P nuclear magnetic resonance spectroscopy (n = 11). Cerebral blood flow (ml.min-1.

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31P NMR brain spectra were obtained from piglets over a range of mild hypocarbia to severe hypercarbia (PaCO225 to 198 mm Hg). The chemical shifts of the phosphoethanolamine and inorganic phosphate were used to calculate intracellular brain pH (pHet and pHpi, respectively). Both pHpi and pHet underwent parallel significant decreases during hypercarbia, corresponding to 51 and 53% pHregulation, respectively.

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