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Biomedical subjects

S M Golden

Publications and source records attributed to S M Golden.

At least 19 recordsLinked to original sources

Cerebral vascular response to hemorrhagic hypotension in newborn lambs: the influence of developing anemia.

The ability of newborn animals to autoregulate cerebral blood flow (CBF) has been documented. Most studies of the cerebral vascular response to hypotension utilize hemorrhage, generally confounded with anemia. We studied the cerebral blood flow and metabolic response of chloralose and urethane anesthetized newborn lambs to regulated hypotension. Lambs (< or = 7 days old) were catheterized for radioactive microsphere determinations of CBF. The dorsal sagittal sinus was catheterized to obtain cerebral blood samples for the calculation of oxygen uptake. Cerebral perfusion pressure was reduced in a step-wise fashion with hemorrhagic hypotension. Animals spontaneously became anemic with hypotension (AH; n = 8). In a group of animals (NH; n = 6), anemia was prevented by infusion of autologous red blood cells. Arterial pressure was reduced from control to 50, 40, and 30 mm Hg. In the AH group hematocrit fell 37% but was not different from control in the NH group. Total CBF was maintained in all groups. The lowest perfusion pressures studied were 25 +/- 1 and 22 +/- 1 mm Hg in AH and NH groups respectively. Oxygen delivery decreased (37%) only in the AH group, secondary to anemia. Calculated oxygen consumption was maintained in the AH group but increased (approximately 50%) in the NH group at 50 and 40 mm Hg. The ratio of oxygen uptake to oxygen delivery (fractional oxygen extraction) increased linearly in both groups as arterial pressure decreased. The major findings of these experiments are (i) The anesthetized newborn lamb can maintain CBF when perfusion pressure falls to 25 mm Hg and this autoregulatory capacity (classically defined) is not dependent on a change in hematocrit and, presumably, viscosity; (ii) Cerebral hypotension, anemic or not, appears to be accompanied by an increase in fractional extraction of oxygen.

Anemia

Pharmacokinetics of intravenous immunoglobulin in neonates.

Intravenous immunoglobulin (IVIG) may be a therapeutic adjunct to antibiotic treatment of neonatal infections. We examined the pharmacokinetics and safety of IVIG in human neonates. Thirty neonates with suspected sepsis were randomly assigned either to a treatment (receiving either 250, 500, or 1,000 mg/kg of IVIG plus antibiotics) or control (antibiotics alone) group. The 500 mg/kg dose produced a rise in total IgG for greater than 8 and in group B streptococcus (GBS) type-specific IgG for greater than 4-14 days. The type-specific antibody elevation varied with the amount of pathogen-specific antibody and dose of IVIG. Pharmacokinetic analysis suggests a Vdss of 42 ml/kg, Cl of 3.0 ml/kg/day, a biphasic elimination curve, and a terminal elimination half-life of 24.2 days. No toxicity was observed. These data may be valuable in determining optimal dosing schedules for IVIG in treating or preventing neonatal infections.

Anti-Bacterial Agents

A group B streptococcal extract reduces neutrophil counts and induces neutrophil aggregation.

The possibility that group B streptococci (GBS) may induce neonatal neutropenia by promoting neutrophil aggregation and the entrapment of aggregates in the lung was studied in vivo and in vitro utilizing a cell free GBS extract [(GBS)-trichloroacetic acid (TCA)]. The intravenous infusion of the extract into neonatal lambs induced reductions of circulating white blood cells (0 time, 3.1 X 10(3)/mm3 +/- 0.5 versus 2.2 X 10(3)/mm3 +/- 0.7) 5 min after infusion (p less than 0.01). At necropsy these lambs had prominent accumulation of polymorphonuclear leukocytes in their pulmonary interstitium. Subsequently, neutrophil aggregation was studied by incubating GBS-TCA in human serum or phosphate-buffered saline with subsequent addition to human polymorphonuclear leukocytes in an aggregometer. GBS-TCA incubated in human serum induced prompt polymorphonuclear leukocyte aggregation (mean delta T 12.3% +/- 2.8 in human serum versus delta T 2.5% +/- 2.1 in phosphate-buffered saline, p less than 0.001). Preincubation of GBS-TCA followed by incubation in human serum with human GBS hyperimmune IgG significantly reduced aggregation (GBS-TCA in serum mean delta T 14.9 +/- 2.44 versus 5.42 +/- 1.80, p = 0.002). Cell-free GBS products may induce polymorphonuclear leukocyte aggregation in the presence of whole serum. This phenomenon might contribute to the pulmonary injury experienced by infants with GBS pneumonia and sepsis.

Animals

Endotoxemia in the neonatal lamb.

Although gram-negative sepsis is a major cause of neonatal morbidity and mortality, our understanding of endotoxemia in the neonate has been hampered by the lack of experimental models. Previous studies have suggested neonatal hyporesponsiveness to endotoxin. We studied unanesthetized neonatal lambs which had been exposed to the environment prior to study. These animals demonstrated the classic early phase changes of endotoxemia including pulmonary hypertension which was dependent upon prostanoid production. This model allows further studies of endotoxemia in the neonate.

Animals

Effect of maternal intravenous infusions on fetal extracellular fluid composition in pregnant ewes.

Infusion of intravenous solutions to women in labor is common clinical practice. Since these infusions may change the volume and electrolyte balance between the mother and fetus, we investigated the influence of acute maternal volume expansion upon fetal and maternal fluid and electrolyte equilibrium in the chronically catheterized fetal lamb. Paired measurements of maternal and fetal plasma sodium and potassium concentrations, osmolality, and colloid osmotic pressure (COP), plus measurements in the fetal-placental plasma volume were obtained following rapid maternal infusions with saline, dextrose, and dextran solutions. Maternal infusions resulted in changes in fetal electrolyte concentrations as well as alterations in transplacental COP differences. Despite these changes, however, no changes in fetal plasma volume were noted.

Animals

Short-term responses in neonatal lambs after infusion of group B streptococcal extract.

Short-term (0 to 30 minutes) physiologic responses of neonatal lambs infused with a trichloroacetic extract of a type III (strain 878) group B streptococcus (878-TCA) were studied. Bolus injections of 878-TCA were associated with pulmonary hypertension, peripheral arterial hypoxemia, and reductions in circulating white blood cell and platelet counts. These events were associated with a rise in plasma levels of prostaglandins F2 alpha and E and could be prevented by proper treatment with ibuprofen. Continuous infusions of 878-TCA were associated with a dose-dependent rise in systemic and pulmonary arterial pressures and a fall in arterial PO2. During infusion, inhibition of prostaglandin synthesis resulted in a return toward preinfusion values. The authors conclude that venous infusions of extracts of 878-TCA induce significant pulmonary and systemic arterial vascular perturbations in the neonatal lamb and that some of these alterations are associated with the release of prostaglandins or other arachidonic acid metabolites.

Animals

Effect of cephalic pressure on fetal cerebral blood flow.

During vaginal delivery, the fetus is exposed to a variety of stresses including pressure applied to the fetal skull. In order to study the effects of this stress on fetal homeostasis, we monitored the response to external cephalic compression applied to the acutely prepared near-term fetal lamb. In response to cephalic pressure, we noted initial bradycardia followed by sustained tachycardia. Mean arterial pressure and pulse pressure rose during cephalic pressure and gradually returned to baseline levels. Cerebral blood flow fell approximately 95% early in the period of compression. This fall in total cerebral blood flow was accompanied by a redistribution of cerebral flow. During this time, a smaller percentage of cerebral blood flow was found in the cortex and a greater percentage was directed to the brainstem.

Animals

Umbilical cord care. A study of bacitracin ointment vs. triple dye.

Umbilical cord colonization rates were examined over a 4-year period following topical application of bacitracin (1978-1980) or triple dye (1980-1982). A total of 2402 cords were cultured: 1229 following bacitracin cord care and 1173 after triple dye application. Cords treated with bacitracin had significantly higher colonization rates when compared to triple dye prophylaxis. Bacterial colonization with Staphylococcus epidermidis and group B beta-hemolytic streptococcus was found only after bacitracin prophylaxis. Our data support the use of triple dye for routine cord care and suggest that bacitracin application may increase the rate of group B streptococcal colonization.

Acridines

Studies of short-term pulmonary and peripheral vascular responses induced in oophorectomized sheep by the infusion of a group B streptococcal extract.

Short-term (0-30 min) pulmonary and systemic vascular responses of oophorectomized ewes infused intravenously with a trichloroacetic acid (TCA) extract of a type III (strain 878) group B streptococcus (GBS) were studied. TCA-878 extract induced significant pulmonary hypertension, reduction in femoral artery pressure and reduced femoral artery PO2. These responses were similar to those observed after the infusion of sublethal doses of E. coli endotoxin and could be prevented by priming the animal with ibuprofen or indomethacin. Ewes rechallenged 48 h after their initial dose of TCA-878 extract experienced pulmonary arterial pressure significantly higher than those induced by the first infusion. Similar augmented responses were not seen after rechallenge with endotoxin. Larger doses of TCA-878 extract resulted in increasingly higher pulmonary arterial pressure. We conclude that the venous infusion of TCA extracts of GBS-878 induces significant pulmonary hypertension in sheep and that this response may be mediated by prostaglandins. The vasoactive substance extracted from these streptococci could play a role in promoting the vascular instability experienced by the human neonate with early onset GBS disease.

Animals

Effect of resuscitative fluids upon physical properties of blood perfusing the brain.

Acute physiologic changes induced by the infusion of resuscitative fluids may be harmful, resulting in the clinical sequelae of pulmonary and intraventricular hemorrhage. Using a chronically catheterized lamb model, changes in plasma sodium concentration, osmolality, hematocrit, glucose, colloid osmotic pressure, and arterial pressure were quantified in blood directly perfusing the brain, following distal infusions of fluids commonly used during neonatal resuscitation: molar and .5M NaHCO3, D10W and D25W, and whole blood. Distal infusion of hypertonic solutions resulted in acute alterations in electrolyte and osmotic equilibrium in the common carotid artery. All infused solutions caused a brief elevation in mean blood pressure; whole blood transfusion resulted in a sustained increase in blood pressure.

Animals

The influence of asphyxia on fetal lidocaine toxicity.

Local anesthetics have played an important role in modern obstetrics. Although reasonably safe, these agents have been shown to have detrimental effects in some fetuses. In the present study we examined the influence of acute asphyxia in the fetal lamb on the distribution and cerebral uptake of maternally infused lidocaine. Results demonstrate that asphyxia is associated with higher lidocaine concentrations in the fetal plasma, increased presentation of the drug to the fetal brain, and increased cerebral lidocaine uptake. These findings underscore the importance of evaluation of fetal status when considering the risks and benefits of maternal drug use.

Animals

Osmolality and oncotic pressure of volume expanding fluids for newborn administration.

Resuscitation of the newborn frequently requires rapid expansion of the circulating volume and correction of metabolic acidosis and hypoglycemia. solutions commonly used for resuscitation contain various concentrations of NaHCO3, glucose, electrolytes, and albumin. We have demonstrated the wide range of osmolalities of solutions frequently available in nurseries and delivery rooms and the resultant osmolalities caused by the addition of NaHCO3. We have also shown the in vitro concentration of albumin needed to equal full-term cord blood colloid osmotic pressure (COP).

Acidosis

Skin craters--a complication of transcutaneous oxygen monitoring.

Continuous transcutaneous oxygen monitoring has become standard practice in the management of infants who require supplemental oxygen. Previously described complications of tcPO2 monitoring consist of prolonged intense skin erythema or first degree burns. Two cases of premature infants who developed numerous, hyperpigmented skin craters following prolonged tcPO2 monitoring are reported. Although these lesions appear to be harmless, they have not resolved with time and long-term cosmetic implications are unknown.

Burns