David E Fisher

Effects of positive pressure ventilation on intrarenal blood flow in infant primates.

Extract: Measurement of intrarenal distribution of renal blood flow by injection of radionuclides in 3—5-day-old infant monkeys showed a preponderance of outer cortical over inner cortical flow with flow rates of 4.23 and 2.54 ml/min/g, respectively. Intermittent positive pressure ventilation (IPPV) causes a reversal of this flow pattern. The theoretical difference in nephron function in these two areas suggests that this reversal in intrarenal flow induced by IPPV may have important clinical implications.Speculation: Extrarenal stimuli such as IPPV causes a redistribution of intrarenal blood flow in infant primates. Any stimuli that results in increased production of epinephrine or similar compounds may be responsible for this redistribution by a local effect on outer cortical blood vessels. Our data further suggest that antidiuretic hormone may influence intrarenal blood flow in addition to altering tubular membrane permeability.

Early state organization and follow-up over one year

Evaluations of state organization at 36 weeks postconceptional age (PCA) were conducted in the special care nursery on 24 low birth weight preterm neonates who were subsequently assessed on three dimensions of outcome at 1 year postterm. Half the subjects (N = 12) had been cared for in an alternative supportive nursery from 32 to 36 weeks PCA; the other half had remained in the regular intermediate care nursery. Although subjects from the alternative nursery demonstrated superior state organization before nursery discharge at 36 weeks PCA (p < .05), they were not superior on any outcome measures at 1 year postterm. Subjects demonstrating superior state organization within their nursery group were compared with subjects demonstrating inferior state organization within their nursery group. Significant differences in 1-year outcome were found between these two groups of good and poor neonatal state organizers on gross morbidity, on the Bayley motor scale, and on a measure of recovery of state organization observed in the Strange Situation (p < .05). J Dev Behav Pediatr 13:83–88, 1992.

The effect of phenobarbital on asphyxia in the newborn monkey.

Extract: This study characterizes the circulatory changes associated with asphyxia in the newborn monkey and examines the effect of phenobarbital on asphyxia. The time to last gasp and duration of total asphyxia as well as heart rate at the start of resuscitation were the same in the phenobarbital-treated and untreated infants. Initial cardiac output was the same in both groups; there was a profound drop in cardiac output with asphyxia which was the same in both groups. Organs which preferentially receive a greater percentage of cardiac output during asphyxia are heart, total brain, and adrenal glands. Organs receiving a decreased percentage of cardiac output during asphyxia are kidneys, liver, and gastrointestinal tract. Cerebral hemisphere flow as a percentage of cardiac output is maintained during asphyxia, whereas paleoencephalon flow as a percentage of cardiac output increases significantly. These data confirm the circulatory redistribution of cardiac output in response to asphyxia described previously in the monkey fetus. The treated infants did not show the prolongation of time to last gasp reported in the monkey fetus; the dose of phenobarbital we used, although adequate to produce sedation, may have been too low to demonstrate the protective effect.Speculation: The long term survival status of infants with neonatal diseases such as severe meconium aspiration or hyaline membrane disease which are frequently accompanied by varying degrees of asphyxia might be improved by including phenobarbital in the treatment regimen if a protective effect were conclusively demonstrated.

Organ blood flows of fetal and infant baboons

Baseline values for total and selected regional blood flows are presented for 77 studies of baboons from 92 days of gestation to 61 days of postnatal age. Systemic blood flow rose from 231.3 +/- 21.4 ml/min/kg to 330.4 +/- 122.4 ml/min/kg in late gestation and from 124.0 +/- 29.9 ml/min/kg on day 1 to 162.8 +/- 20.5 ml/min/kg at the 8th week. In both fetal and infant periods, blood flow to brain, heart, kidneys, and gastrointestinal tract changed to reflect both anatomic and functional requirements. When compared to late gestation levels, blood flows on day 1 to brain, myocardium and gastrointestinal tract decreased proportionally to systemic blood flow. In contrast, renal blood flow on day 1 was maintained at the predelivery level and represented about twice the proportion of systemic blood flow of late gestation. The data presented provide a developmental profile of systemic and selected organ blood flows from mid-gestation to the 8th week of postnatal life in the baboon. As such, they may form the basis for further investigation and understanding of perinatal maladaptation from preterm delivery and disease.

Gluconeogenesis from Lactate in the Chronically Catheterized Baboon Fetus

Gluconeogenesis from lactate may be qualitatively identified in the chronically catheterized baboon fetus in the maternal fed and fasted state. Infusion of 250 microCi U-14C-lactate to the fetus over a 150-min period leads to the appearance of 14C-glucose in the fetal circulation. Little 14C-lactate or glucose appears in the maternal circulation, supporting fetal production of glucose from lactate. Maternal glucose infusion seems to inhibit fetal gluconeogenesis. The mean plateau in percent disintegrations per minute of glucose compared to lactate in the maternal fed state is 14.7 +/- 2.2 compared to 16.1 +/- 3.0 in the maternal fasting state and 11.1 +/- 0.6 during maternal glucose infusion. It is clear that the primate fetus is capable of gluconeogenesis before term. Quantitation of this capacity awaits development of a model permitting assessment of maternal-placental and fetal substrate flux.

A canonical arithmetic quotient for actions of lattices in simple groups

In this paper we produce an invariant for any ergodic, finite entropy action of a lattice in a simple Lie group on a finite measure space. The invariant is essentially an equivalence class of measurable quotients of a certain type. The quotients are essentially double coset spaces and are constructed from a Lie group, a compact subgroup of the Lie group, and a commensurability class of lattices in the Lie group.

Placental Transfer and Fetal Effects of Maternal Sodium ß -Hydroxybutyrate Infusion in the Baboon

ABSTRACT: We examined the effects of maternal sodium ß-hydroxybutyrate (NaBOHB) on the primate fetus to investigate the impact of ketosis not associated with acidosis on fetal metabolism. After a loading dose (600 mg/ kg), NaBOHB was infused for 70 min (300 mg/kg hr) into the maternal femoral vein of eight pregnant baboons, and placental transfer and fetal and maternal metabolic changes were observed during an acute experimental protocol. Maternal arterial levels rose from 0.70 ± 0.21 to 5.42 ± 0.93 mM (p<0.001), and fetal arterial levels from 0.34 ± 0.09 to 2.76 ± 0.64 mM (p<0.01). A maternalfetal gradient of approximately 2:1 was observed in both baseline and steady-state infusion conditions and is similar to the human maternal-fetal ketone gradient. This is in contrast to the sheep where significantly higher gradients have been described. The elevated lactate, from 1.90 ± 0.34 to 2.88 ± 0.54 mM (p<0.05) and somewhat decreased pO2 values in the fetus from 54.8 ± 8.9 to 45.0 ± 3.8 mm Hg (p>0.05<0.1), without change in oxygen consumption (2.00 ± 0.28 versus 1.73 ± 0.15 mM/min) are features common to conditions of increased levels of fetal energy substrate. NaBOHB does not appear to contribute to oxidative energy metabolism of the whole fetus but may contribute to lipid stores. The significance of higher levels of BOHB in the primate fetus compared to the sheep fetus remains to be elucidated.

Splanchnic Uptake and Release of Energy Substrates in the Fasting Baboon Infant

ABSTRACT: Estimates of splanchnic energy substrate exchange in the primate infant have been obtained using a baboon model. The splanchnic bed of the fasting baboon newborn released glucose at an estimated rate of 14.5 ± 5.0 μmol/min·kg body weight. Splanchnic glucose release in the fasting 5-7-wk old baboon infant proceeded similarly at an estimated rate of 15.5 ± 4.5 μmol/min·kg body weight. The principal precursors taken up by the splanchnic bed were lactate, glycerol, and alanine. Uptake of alanine correlated in a linear fashion with glucose release. Lactate was the most important precursor in both age groups. Glucose recycling through lactate is an active mechanism in the primate fetus as well as in the young of other species.

Arterial blood levels of energy substrates and evidence for renal glucose production in the baboon infant.

Summary: The age-related changes in fasting arterial levels of energy substrates and insulin were studied at birth and/or 6 wk in eleven baboon infants. In addition, the renal contribution to glucose release in the primate infant was estimated. Arterial blood glucose levels were similar in six fasted newborns and in nine fasted 6-wk-old infants. Arterial blood lactate, alanine, pyruvate, glutamate, and glutamine levels were significantly higher (P < 0.01) in the new born animals, and β-hydroxybutyrate was significantly higher in the older animals (P < 0.001). Arterial plasma insulin levels were low in both groups. Levels of blood glucose in the inferior vena cava below the renal vein were significantly lower than levels in the aorta (P < 0.01). In contrast, levels of blood glucose in the inferior vena cava above the renal vein were significantly higher than in the aorta (P < 0.05). Computed renal vein glucose levels were higher than those in the aorta (P < 0.01). In the newborn infants, there was significant renal uptake of lactate, pyruvate, glycerol, and glutamine (P < 0.01), and release of β-hydroxybutyrate (P < 0.05). In the older animals, there was renal uptake of alanine, lactate, pyruvate, and glycerol (P 0.01). Mean cardiac output per kg body weight did not differ significantly in the newborn and 6-wk-old infants.Lactate uptake was potentially responsible for 59% of mean renal glucose output in the newborn and 76% of mean renal glucose output in the older infant. Net renal glucose release in eight 6-wk-old infants was estimated to be 3.5 ± 1.1 μM/min · kg (95% confidence limits, 0.7 < 3.5 < 6.2). Net renal glucose release in three newborn infants was 4.7, 5.4, and 19.8 μM/min · kg. There was a significant linear relationship between arterial lactate levels and renal glucose production in the older infants (P < 0.05). Extremely low arterial pH was associated with increased renal glucose release in the newborn, and high arterial pH with decreased or absent glucose release in the 6-wk-old animals.Speculation: The primate infant kidney has a capacity for gluconeogenesis which is apparently enhanced by acidosis and lactate availability. In the stressed human neonate, it is possible that renal gluconeogenesis could be a significant and uncontrolled source of new glucose, leading to hyperglycemia.

BASE DEFICIT DURING CITEIPC ARREST SECONDARY TO RESPIRATORY FAILURE IN IMMATURE PIGS

Recent studies suggest that NaHCO3 may be detrimental in treatment of cardiac arrest from ventricular fibrillation. The American Heart Association (AHA) recomnerds limited use of NaHCO3 (initial dose 1 mEq/kg). In children respiratory failure is the major cause of cardiac arrest; so these studies may not apply. The purpose of our study was to determine base deficit (-BE) at the time of cardiac arrest due to respiratory failure in immature pigs. 10 minipigs (8.0-9.5kg) were anesthetized with pentobarbital and ventilated. Catheters were placed in the aorta and pulmonary artery. The erdotracheal tubes were clamped (9.3±3.1 min) to produce asphyxia causing electromechanical dissociation (EMD) (Aortic pressure (PAo)<30 mmHg). (PAo), arterial blood gases and lactates were measured during a baseline (BL), at time of EMD and 3 min of EMD (EMD3)All piglets developed metabolic acidosis that would require at least 6 mEq/kg of NaHCO3 for partial correction (-BEx Weight in kg x0.3). We conclude that cardiac arrest secondary to respiratory failure results in a -BE which is not treated with resuscitation practiced according to current AHA guidelines.