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A R Laptook

Publications and source records attributed to A R Laptook.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effect of plasma glucose concentration on cerebral metabolism during partial ischemia in neonatal piglets.

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. Plasma glucose concentration showed a significant linear correlation with intracellular pH (r = -0.7, p less than 0.05). Piglets that developed hypoglycemia during partial ischemia had a smaller reduction in intracellular pH and a larger increase in inorganic phosphate content than piglets that were normoglycemic or hyperglycemic during ischemia. Similar differences persisted during the first 5 minutes of postischemic reperfusion. Subsequently, the cerebral concentrations of phosphorylated compounds returned to normal in all piglets. Our results demonstrate that 1) arterial plasma glucose concentration influences cerebral energy metabolism and intracellular pH during ischemia, 2) neonatal piglets can develop profound brain acidosis, and 3) brain acidosis during ischemia does not influence the restoration of cerebral phosphorylated compounds to control levels during the first 90 minutes after ischemia.

Adenosine Triphosphate↗
PubMed1989

Use of 31P magnetic resonance spectroscopy to characterize evolving brain damage after perinatal asphyxia.

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. MRS noninvasively provides biochemical correlates of the evolution of brain damage following perinatal asphyxia and suggests that pH derived from the inorganic phosphate peak may serve as a marker for brain injury.

Asphyxia Neonatorum↗
PubMed1988

Quantitation of acidosis in neonatal brain tissue using the 31P NMR resonance peak of phosphoethanolamine.

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. We conclude that the chemical shift of the phosphomonoester peak in vivo can be used to measure decreases in intracellular pH in neonatal brain.

Acidosis↗
PubMed1988

Effects of repeated ischemia on cerebral blood flow and brain energy metabolism.

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. Control values of all variables were similar during protocol A and B. In each protocol hypotension was associated with similar reductions in CBF and cerebral O2 uptake but cerebral glucose uptake differed (0.10 +/- 0.05 vs 0.05 +/- 0.02 mmol.min-1.100 g-1 during hypotension of A and B, respectively, p less than 0.05). During hypotension of protocol A and B similar changes in phosphorylated metabolites and pHi occurred and were characterized by a reduction in pHi, phosphocreatine and adenosine triphosphate and an increase in inorganic phosphate. Changes in phosphate metabolites and pHi were reversible within 25 min following hypotension in both protocols. Thus, changes in CBF, cerebral O2 uptake, pHi and cerebral energy metabolism are similar during repeated episodes of partial ischemia. However, differences in cerebral glucose uptake in protocol A and B raise the possibility that the balance between energy production and utilization is altered, or alternative substrates are metabolized or enzymatic activity in the glycolytic pathway is changed.

Animals↗
PubMed1988

Effects of lactic acid infusions and pH on cerebral blood flow and metabolism.

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 (7.50 +/- 0.02 vs. 7.49 +/- 0.02, X +/- SE); during and following L + NaCl and L + NaOH, values were (p less than 0.05) 7.09 +/- 0.03, 7.35 +/- 0.02, and 7.46 +/- 0.02 vs. 7.58 +/- 0.03, 7.61 +/- 0.01, and 7.57 +/- 0.03, respectively. PaCO2 remained unchanged and osmolality rose by 15% in both groups during infusions and persisted throughout the study period. For L + NaCl piglets, CBF (ml/min.100 g) rose from 136 +/- 15 to 198 +/- 26 (p less than 0.05) at 30 min of infusion and remained elevated at 201 +/- 25 and 207 +/- 28 at 15 and 90 min following the infusion, respectively. Similarly, for L + NaOH piglets, CBF rose from 130 +/- 25 to 196 +/- 31 (p less than 0.05) with the infusion and was 174 +/- 17 and 166 +/- 21 at 15 and 90 min afterward, respectively. Although lactic acid infusion increases CBF, the associated metabolic acidemia is not responsible for changes in CBF.

Animals↗
PubMed1988

Intracellular pH, lactate, and energy metabolism in neonatal brain during partial ischemia measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy.

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. In four piglets, whose arterial blood glucose rose above control, brain lactate exceeded 20 mumol g-1 with corresponding decreases in pHi of greater than 0.7 units compared to control levels. The extents of brain acidosis and lactosis showed a strong linear correlation with each other (r = 0.94). Maximal changes in brain lactate, pHi, and ATP at the end of ischemia showed significant positive linear correlations with the control levels of arterial blood glucose, but did not correlate with arterial glucose or arterial cerebral-venous glucose difference values during ischemia. The relationship between pHi and buffer base deficit was comparable to results reported for adult animals up to 20 mumol ml-1. However, in contrast to models proposed for adult brain, the continued linear relationship between pH and higher buffer base levels is most consistent with a theoretical model that assumes the presence of weak acid buffers with pKa values from 6.7 to 5.2.

Adenosine Triphosphate↗
PubMed1988

Increased fetal secretion of ACTH and cortisol by arginine vasopressin.

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., acting as a corticotropin-releasing factor, an effect not clearly demonstrated in the fetus. Therefore we examined this action of AVP in fetal sheep [135 +/- 1 (SE) days gestation] during a 30-min vasopressin infusion (12 mU/min) while monitoring mean arterial pressure (MAP) and heart rate (HR). Blood samples were obtained before, 15 and 30 min during, and 30 and/or 60 min after the infusion. During vasopressin infusion (n = 11), MAP increased (P less than 0.01), whereas HR fell (P less than 0.01). Plasma AVP increased from 2.32 +/- 0.22 to 84 +/- 6.8 and 89 +/- 10 microU/ml (P less than 0.001), whereas adrenocorticotropin (ACTH) rose from 18.0 +/- 2.4 to 27.7 +/- 3.7 and 43.4 +/- 8.0 pg/ml (P less than 0.05) and cortisol from 1.81 +/- 0.36 to 3.48 +/- 0.56 and 3.97 +/- 0.57 micrograms/dl (P less than 0.005) at 15 and 30 min, respectively. Although neither basal nor AVP-induced ACTH increases changed over the period of gestation studied, base-line cortisol concentrations and the absolute rise in ACTH-stimulated cortisol release increased as gestation progressed, demonstrating increased adrenal sensitivity to ACTH. As in adults, AVP stimulates fetal pituitary secretion of ACTH, providing evidence for another role for AVP in fetal adaptation.

Adrenocorticotropic Hormone↗
PubMed1988

Alterations in cerebral blood flow and phosphorylated metabolites in piglets during and after partial ischemia.

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-1.100 g-1) decreased during hypotension (98 +/- 28 to 41 +/- 28, p less than 0.05), increased at 5 min postreperfusion (131 +/- 53, p less than 0.05), and returned to control values by 90 min postreperfusion. Cerebral O2 uptake was reduced during partial ischemia, remained depressed 5 min postreperfusion, and increased to within 20% of control values at 90 min postreperfusion. Relative to control, hypotension was associated with decreased (p less than 0.05) phosphocreatine (62 +/- 11%), phosphocreatine/inorganic phosphate ratio (41 +/- 10%), and nucleoside triphosphate (82 +/- 12%) while inorganic phosphate increased (155 +/- 32%, p less than 0.05). During ischemia intracellular pH dropped from 7.06 +/- 0.07 to 6.59 +/- 0.31 (p less than 0.05) and the cerebral arteriovenous difference of glucose increased. Phosphorylated metabolites returned to within 10% of control 15 min after blood reinfusion and remained constant thereafter. Based on calculations of ATP synthesis and utilization rates during control and hypotension, we speculate that the rate of energy utilization of the brain during ischemia is reduced 18-49% relative to the control utilization rate.

Animals↗
PubMed1987

Vasopressin and catecholamine secretion during metabolic acidemia in the ovine fetus.

It has been suggested that the substantial rise in fetal plasma arginine vasopressin (AVP) during intrauterine hypoxia/asphyxia reflects decreases in PaO2 and/or pHa; however, the components of these "stresses," i.e. PO2, PCO2, and pH, have not been controlled. Recently, only modest increases in fetal AVP secretion were seen during hypoxia independent of changes in pH and PCO2. Since the independent effects of metabolic acidosis on fetal AVP secretion are unknown, we induced acute metabolic acidemia in fetal sheep at 137 +/- 4 (mean +/- SD) days gestation with 1 M NH4Cl, while monitoring mean arterial pressure, heart rate, PaO2, PaCO2, pHa, plasma osmolality, and blood concentrations of electrolytes, AVP, dopamine, norepinephrine, and epinephrine. Mean arterial pressure, PaO2, PaCO2, and plasma osmolality and sodium were unchanged; pHa decreased from 7.37 +/- 0.01 to 7.04 +/- 0.05 (p less than 0.05) during NH4Cl and did not return to control levels until 24 h later. AVP increased from 2.85 +/- 0.23 to 5.26 +/- 1.11 microU/ml (p less than 0.05) at the time of maximum acidosis, correlating with the fall in pHa (r = -0.67, (p = 0.001); however, after stopping NH4Cl, AVP returned to baseline levels although pHa remained less than 7.15. In control studies using the same osmolar load, volume, and rate of infusion, AVP levels were unchanged. Only epinephrine was significantly (p less than 0.05) elevated during acidosis, but did not correlate with pHa or plasma AVP. Marked metabolic acidemia appears to have little or no effect on fetal AVP secretion, and fetal catecholamine secretion is variable.

Acidosis↗
PubMed1987

The use of the chemical shift of the phosphomonoester P-31 magnetic resonance peak for the determination of intracellular pH in the brains of neonates.

The use of the chemical shift of the phosphomonoester P-31 magnetic resonance peak for the determination of intracellular pH has been assessed for piglet and neonatal human brain in vivo. The chemical shift difference between resonance peaks corresponding to phosphoethanolamine and inorganic phosphate, compared with phosphocreatine, was determined for piglets and human neonates. Using in vitro pH titration data to calculate intracellular pH, it was found that pH values from the phosphoethanolamine peak (pH 6.84 to 6.80) were lower than pH estimates from the inorganic phosphate peak (pH 7.22 to 6.99). This difference suggests that phosphoethanolamine and inorganic phosphate may exist in different intracellular environments. Results are presented to demonstrate that the phosphomonoester peak may also be used to measure changes in intracellular pH associated with brain ischemia.

Animals↗
PubMed1987

Cerebral lactic acid delivery and uptake during and after ischemia in the piglet.

To determine whether lactic acid is a cerebral substrate during and after partial ischemia in piglets, cerebral blood flow and arteriovenous differences of O2 and substrates were measured during control, after hemorrhagic hypotension, and 10 and 90 minutes after reperfusion with blood. During and following ischemia, alterations in cerebral O2 and glucose uptake indicated disturbed oxidative metabolism. Cerebral lactic acid uptake was similar at control, hypotension, and 90 minutes postreperfusion, but rose 10 minutes postreperfusion. Absent cerebral production of lactic acid during and net uptake following ischemia do not support lactic acid as a substrate since insufficient O2 was available for oxidation.

Animals↗
PubMed1985

Cerebral vascular responses to tolazoline infusions in the piglet.

Ventilated piglets were studied to determine the effects of intravenous tolazoline infusions during hypoxia on the cerebral circulation and to assess whether cerebral responses reflect tolazoline-induced alterations in the systemic vasculature. We measured cerebral blood flow (CBF), cardiac output (CO), mean arterial pressure (MAP) and cerebral arteriovenous differences of O2 content during normoxia, isocapnic hypoxia (FiO2 14%), and hypoxia (FiO2 14%) with infusions of either saline (n = 7) or tolazoline (n = 10). Hypoxia alone resulted in comparable cardiovascular alterations in both groups. During hypoxia + saline MAP remained stable, but decreased during hypoxia + tolazoline, reflecting reductions in systemic vascular resistance (SVR) and variable changes in CO (reductions in 4 piglets, increases in 6). In both groups CBF rose during hypoxia alone and remained elevated during hypoxia with saline or tolazoline. Cerebral O2 delivery, extraction and uptake were unchanged in both groups. Although mean CBF was similar during hypoxia with saline or tolazoline, CBF was variable during tolazoline, decreasing in 4 of 10 piglets; CBF never fell with saline. Tolazoline-induced changes in MAP correlated with CBF (r = 0.90, P less than 0.001) emphasizing the importance of MAP in maintaining CBF during hypoxia. Importantly, decreases in CBF also paralleled falls in CO. In the presence of a pressure-passive cerebral vasculature, the adequacy of increases in CO to offset tolazoline-induced reductions in SVR determines MAP and ultimately CBF. Thus, cerebral vascular responses to tolazoline infusions during hypoxia reflect tolazoline-induced systemic circulatory derangements.

Analysis of Variance↗
PubMed1985

The effects of sodium bicarbonate on brain blood flow and O2 delivery during hypoxemia and acidemia in the piglet.

Metabolic acidosis in the neonate is often secondary to hypoxemia and cardiopulmonary disturbances. Sodium bicarbonate, an agent used to treat metabolic acidemia in newborns, is often administered during hypoxemia. In the absence of acid-base alterations, during hypoxemia a reciprocal relationship exists between arterial O2 content (CaO2) and brain blood flow (BBF). However, when hypoxemia is compounded by acidemia it is unclear whether the increase in arterial pH achieved by infusions of sodium bicarbonate alters BBF. To investigate this, BBF (microsphere technique), arterial blood gases, and CaO2 were measured in 14 ventilated piglets. Variables were assessed during a control period, a period of hypoxemia (50 min) associated with metabolic acidemia (hypoxemia + acidemia), and after infusions of either saline (n = 6) or NaHCO3 (n = 8, 2 mEq/kg) during continued hypoxemia. Arterial pH was similar in both groups at control, and hypoxemia + acidemia resulted in comparable reductions of pH in both saline- and NaHCO3-treated piglets (7.21 +/- 0.02 versus 7.21 +/- 0.03, respectively). NaHCO3 infusions produced a significant rise in pH, 7.30 +/- 0.03 versus 7.15 +/- 0.03, p less than 0.05. In each group CaO2 paralleled changes in pH but did not differ between groups. In all animals BBF increased more than 2-fold during hypoxemia + acidemia and was unaltered by infusions of either saline or NaHCO3. Brain O2 delivery decreased in both groups during hypoxemia + acidemia and was unchanged by infusions of saline or NaHCO3. During hypoxemia + acidemia the change in arterial pH induced by NaHCO3 (2 mEq/kg) does not alter BBF or brain O2 delivery.

Acidosis↗
PubMed1984

The renal response to acute asphyxia in spontaneously breathing newborn lambs.

The effects of acute asphyxia on neonatal renal function were examined in spontaneously breathing newborn lambs. 25 min of asphyxia were induced by addition of a respiratory dead space to reduce PaO2 to 41 +/- 3 mm Hg, pH to 7.03 +/- 0.05 and increase PaCO2 to 68 +/- 5 mm Hg (mean +/- S.E.M.). Glomerular filtration rates did not change significantly during or after asphyxia. Immediately following asphyxia significant (P less than 0.05) increases over the baseline were found in urinary flow rates, fractional sodium excretion, absolute sodium excretion and osmolar clearances. These changes were in part secondary to significant (P less than 0.05) increases in plasma glucose concentrations associated with increases (P less than 0.05) in circulating arterial catecholamine concentrations. The percentage of tubular reabsorption of glucose decreased significantly (P less than 0.05) and urinary glucose excretion increased significantly. Renal blood flow was unchanged. Therefore, asphyxia induced significant hyperglycemia which contributed to the concomitant natriuresis and osmotic diuresis in these newborn lambs.

Acute Disease↗
PubMed1984

In situ PCO2 in the renal cortex, liver, muscle, and brain of the New Zealand white rabbit.

Recent studies have shown that in situ PCO2 in rat renal cortical structures far exceeds systemic arterial PCO2. These results were opposite to previous assumptions that renal proximal tubule fluid PCO2 approximated arterial PCO2. The present studies examined the species and organ specificity of the elevated PCO2 in 39 New Zealand White rabbits studied under normal acid-base conditions. In situ PCO2 was measured in renal cortex, superficial hepatic parenchyma, skeletal muscle, superficial cerebral cortex, and femoral nerve, artery, and vein. The results showed rabbit renal cortical PCO2 (57.2 +/- 1.2 mmHg) to be higher than both systemic arterial (39.1 +/- 2.0 mmHg) and venous PCO2 (45.4 +/- 2.1 mmHg). Similarly, liver PCO2 (64.1 +/- 3.5 mmHg) was found to be significantly higher than systemic arterial and venous PCO2 and also higher than portal and hepatic vein PCO2. Skeletal muscle, cerebral cortex, and femoral nerve PCO2 levels were usually greater than systemic arterial PCO2 but less than systemic venous PCO2. These observations show that in situ PCO2 is significantly elevated above afferent and efferent blood PCO2 in the kidney and liver but not in muscle or brain. A possible explanation for these findings in the former two organs may be high CO2 production and/or trapping of CO2 by their vascular systems.

Animals↗
PubMed1984

Chloral hydrate toxicity in a preterm infant.

Ventilator care in premature infants with hyaline membrane disease (HMD) may be complicated by episodes of irritability and "fighting" the respirator, resulting in significant hypoxemia. Neuromuscular blockade with pharmacologic agents such as pancuronium bromide is frequently used to manage this problem [Crone and Favorito, 1980]. This therapy results in the loss of important clinical signs, such as alterations in muscle tone and spontaneous movements, which are important in monitoring the critically ill newborn. As a result of these considerations, we occasionally have utilized the sedative-hypnotic effects of chloral hydrate to achieve adequate ventilation and oxygenation in these infants. We report, however, a case of a preterm infant who developed severe chloral hydrate toxicity after its administration as an adjunct to the treatment of HMD.

Chloral Hydrate↗
PubMed1983

The effect of carotid artery ligation on brain blood flow in newborn piglets.

The common carotid artery is often ligated and used to introduce a left ventricular catheter to perform blood flow studies with radioactive-labeled microspheres. In order to determine whether this procedure alters brain blood flow, 6 newborn piglets were studied. Five measures of brain blood flow were performed in each study; once before and then 4 times (at 20 min intervals) after ligation of the left common carotid artery. Ventilation was controlled using nitrous oxide and oxygen while the hematocrit was kept stable by intermittent transfusions. Brain blood flow was found to remain constant over the duration of the study. No differences in blood flow were found between the right and left sides of the brain. The data indicate that use of a common carotid artery for purposes of left ventricular catheterization do not alter the blood flow to the brain when the microsphere method is used. This facilitates surgical preparation when small animals are used for studies of brain blood flow hemodynamics.

Animals↗