Biomedical subjects
Publications and source records attributed to H Bard.
Fetal hemoglobin (HbF) synthesis in children with congenital cyanotic heart disease was compared that in normal children. Children with hypoxemia had higher levels of hemoglobin, total HbF, and HbF synthesis. In these children there was also an inverse correlation between HbF synthesis and oxygen content, as well as between HbF synthesis and hemoglobin concentration. Thus hypoxemia increases HbF synthesis.
We determined the effects of anemia of prematurity on myocardial, metabolic, and erythropoietic functions. Twelve anemic (hemoglobin range, 65 to 78 gm/L) infants without symptoms (gestational age, (mean +/- SD) 28 +/- 2 weeks; birth weight, 1178 +/- 326 gm) were studied at a postconceptional age of 35 +/- 1.6 weeks. All measurements were done before and 36 to 48 hours after a transfusion of packed erythrocytes. Cardiac output, heart rate, and myocardial function were assessed. Oxygen consumption, carbon dioxide production, resting energy expenditure, arterial oxygen pressure for 50% hemoglobin saturation, and the concentrations of erythropoietin and 2,3-diphosphoglycerate were also determined. After transfusion, increased hemoglobin level (75 +/- 4 to 150 +/- 16 gm/L) and decreased oxyhemoglobin affinity (20.8 +/- 1.7 to 23.6 +/- 2.1 gm/L; p < 0.05) caused a decrease in plasma erythropoietin concentration (from 21.1 +/- 6.2 to 5.8 +/- 1.5 mU/ml; p < 0.01). There was a decrease in heart rate (from 155 +/- 10 beats/min to 146 +/- 7 beats/min) and cardiac output (from 281 +/- 73 ml/kg per minute to 199 +/- 62 ml/kg per minute; p < 0.05). Myocardial function indexes, weight gain, and metabolic demands were normal before and after transfusion. These results suggest that oxygenation is adequately maintained in symptom-free infants with anemia of prematurity.
Increased fetal Hb (HbF) synthesis has been shown to occur during fetal hypoxemia and severe anemia. To determine whether increased HbF synthesis occurs during anemia of prematurity, the levels of HbF synthesis were correlated with the degree of anemia and plasma erythropoietin levels. Thirteen newborn infants born at 29.2 +/- 1.7 wk of gestation were studied at a postconceptional age 36.0 +/- 1.1 wk. Hb levels ranged from 65 to 78 g/L. Blood samples were incubated in an amino acid mixture containing [3H]leucine and chromatographed allowing the separation and quantitation of the alpha, beta, and gamma (A gamma T, G gamma, and A gamma I) chains. Erythropoietin was determined by RIA. The mean HbF synthesis was 77.9 +/- 8.9% of total Hb synthesis (range: 61 to 91%). Plasma erythropoietin concentrations were 21.4 +/- 6.4 mU/mL. There was no correlation between the total Hb or HbF synthesis and the level of erythropoietin. There was, however, a significant inverse correlation between the Hb level and HbF synthesis (p < 0.01). Nine infants who had received transfusions during the first few days of life had a mean HbF that was 53.5 +/- 15.2% of total Hb, whereas their HbF synthesis was 78.4 +/- 7.6%. Four of the infants never received transfusions; the total circulating HbF and HbF synthesis in these infants were 87.7 +/- 7.7% and 76.8 +/- 12.7%, respectively. This study shows that there can be a reactivation of HbF synthesis during severe anemia of prematurity.
Explore the source record for details and available documents.
Since very low birth weight preterm newborns are prone to oxygen toxicity and have red blood cells that have a high oxygen affinity, the knowledge of the P90 (the PaO2 required for 90% saturation of hemoglobin) could result in a more optimal oxygenation. This information could diminish the incidence of bronchopulmonary dysplasia and retrolental fibroplasia. To determine P90 and P50 (the PaO2 required for 50% saturation of hemoglobin), cord blood was obtained from 10 preterm newborns who were of less than 30 weeks' gestation (26.4 +/- 1.4 [SD] weeks) weighing less than 1000 g (816 +/- 119 g). The P50 and P90 were determined by gas mixing tonometry and expressed in millimeters of mercury at a temperature of 37 degrees C, a pH of 7.40, and PCO2 of 40 mm Hg. The tonometer permitted an equilibration and sampling of successive aliquots of blood at different oxygen tensions. Measurement of oxygen saturation, pH, and PaO2 provided the information for plotting the oxygen dissociation curve, the P50 and P90. There were at least six experimental points for each oxygen dissociation curve. The results showed that the mean P50 was 18.3 +/- 1.9 mm Hg (2.5 +/- 0.3 kPa) and the P90 was 40.8 +/- 3.6 mm Hg (5.4 +/- 0.5 kPa). This study demonstrates the fetal nature of the oxygen dissociation curve of very low birth weight newborns; but most importantly it also shows that when treating very low birth weight newborns with oxygen, a PaO2 of 41 mm Hg (5.5 kPa) is enough to saturate 90% of the hemoglobin at a physiological pH. This information could be of clinical importance to minimize oxygen toxicity.
Little information is available on the energy expenditure of infants with increased work of breathing from respiratory distress syndrome (RDS). A study was carried out to determine whether surfactant replacement therapy modifies respiratory gas exchange in newborn infants with RDS and an arterial-alveolar oxygen tension ratio of less than 0.22. In a double-blind, placebo-controlled, rescue trial, infants received either two 5 ml/kg doses of a synthetic surfactant, Exosurf Neonatal, or air placebo. Of 23 infants ventilated for RDS, 11 were randomly assigned to receive air and 12 to receive surfactant. Oxygen consumption, carbon dioxide production, respiratory quotient, and metabolic rate were measured by computerized, closed-circuit, indirect calorimetry. Concomitantly, transcutaneous oxygen and carbon dioxide tension were continuously recorded. Oxygen consumption and carbon dioxide production remained constant during the period infants received surfactant. In patients randomly assigned to surfactant, a decrease in respiratory quotient was observed after the first (p less than 0.025) but not the second dose. This decrease was possibly related to a change in substrate utilization. The improved clinical outcomes reported among infants receiving surfactant were not accompanied by changes in energy expenditure.
This study was carried out to investigate the effect of fetal hypoxemia, as a result of acute intermittent maternal hypoxia, on the switchover from fetal to adult type Hb as well as Hb oxygen affinity and 2,3-diphosphoglycerate levels in the near-term fetus. These experiments were carried out using 10 fetal lambs with gestational ages ranging from 132 to 140 d. After the installation of appropriate fetal catheters, five of the ewes were exposed to an air mixture containing 10% O2 for 90 min/d for 4 consecutive d. Blood samples were withdrawn before the beginning of the hypoxic experiments and between the 5th and 6th d after the first episode of hypoxia. These samples were for the determination of 2,3-diphosphoglycerate concentration, arterial O2 pressure at which Hb is 50% saturated, and Hb type synthesis. Blood gases were monitored during each hypoxic episode. During the hypoxia, fetal arterial O2 pressure decreased from 2.43 +/- 0.36 kPa (18.2 +/- 2.7 mm Hg) to 1.57 +/- 0.17 kPa (11.8 +/- 1.3 mm Hg). These values returned to their initial levels after cessation of the maternal hypoxia. Five control animals of the same gestational age were also followed. During the interval of the study, a decrease of fetal Hb synthesis was noted (71.7 +/- 12.1 to 57.4 +/- 10.2%, p less than 0.001) in the control group. However, the level of fetal Hb synthesis did not significantly change in the hypoxic group (85.1 +/- 11.1 versus 80.6 +/- 18.9%).(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Since the ovine model is the most commonly used for foetal haemodynamic investigation it was felt important 1) to investigate the technical difficulties involved with ultrasound fetal cardiac imaging in this species and 2) to establish normal reference values for ovine cardiac and umbilical blood flow velocity measurements. Both two-dimensional and pulsed Doppler techniques were used for this assessment in 25 unsedated ewes. All morphological features described in human features to identify the ventricular cavities could be found in the ovine fetus with the two-dimensional echocardiogram. Specific differences included a flatten thorax as visualized from the lateral position, the mesocardial position of the heart, and a large left azygos vein behind the left atrium draining blood into a dilated coronary sinus. The mean peak velocities (cm/sec) of the early diastolic wave (E) and the atrial wave (A), along with their calculated ratio, were not statistically different between the two atrio-ventricular valves (E: 30.6 +/- 6.6, 31.2 +/- 6.1; A: 43.0 +/- 8.3, 41.6 +/- 8.0; E/A: .72, .76 for mitral and tricuspid valves respectively). A significant difference was observed between the acceleration times of the blood ejected into the aorta and the pulmonary artery, with the time interval being shorter in the pulmonary artery (Aorta: 0.052 +/- 0.011; Pulmonary artery: 0.037 +/- 0.009 s). A mean pulsatility index of the umbilical artery of 0.89 was recorded. The data recorded in this study should serve as a reference base for further non-invasive studies of the ovine foetal circulatory system using the ultrasound technique.
BACKGROUND: Surfactant-replacement therapy is now recognized as a life-saving and safe intervention in small premature infants, but there is little evidence concerning its risks and benefits in larger premature infants. METHODS: We conducted a placebo-controlled, blinded trial in 1237 infants with respiratory distress who were enrolled at 23 hospitals in the United States and 13 hospitals in Canada. At entry all the infants weighed at least 1250 g, were receiving mechanical ventilation, and had a ratio of arterial to alveolar oxygen tension below 0.22. The initial dose of either the synthetic surfactant (Exosurf, 5 ml per kilogram of body weight) or air (the placebo) was administered less than 24 hours after birth, with a second dose given 12 hours later. A total of 614 infants were assigned to receive surfactant, and 623 to receive placebo. RESULTS: Fewer infants in the surfactant group than in the placebo group died before 28 days of age or survived at 28 days with bronchopulmonary dysplasia (7 percent vs. 12 percent, P = 0.002). In the first 28 days of life, there were fewer deaths due to respiratory distress syndrome in the surfactant group (1 percent vs. 3 percent, P = 0.043), lower overall neonatal mortality (4 percent vs. 7 percent, P = 0.04), and a lower incidence of bronchopulmonary dysplasia (3 percent vs. 6 percent, P = 0.008). There was also a significantly lower incidence of pulmonary air leaks, intraventricular hemorrhage, patent ductus arteriosus, seizures, hypotension, and pulmonary hypertension in the surfactant group. The infants treated with surfactant were weaned from oxygen and mechanical ventilation significantly sooner than those given placebo, and they less often required high-frequency ventilation or extracorporeal membrane oxygenation. The primary side effect observed more frequently among the infants who received surfactant treatment was pulmonary hemorrhage (six infants vs. one infant, P = 0.055). CONCLUSIONS: In infants weighing at least 1250 g at birth who have respiratory distress syndrome, treatment with two doses of synthetic surfactant improves survival and reduces perinatal morbidity.
We speculated that a relationship may exist between transient peripheral pulmonary stenosis and the closure of the ductus arteriosus. Fifty preterm infants had pulmonary artery and ductal color Doppler flow velocity assessments performed before and after closure of the ductus arteriosus. No flow turbulence or increase in velocity was observed immediately after birth, although a significant discrepancy in size was observed between the main pulmonary artery and its two branches. After closure of the ductus, 15 infants had signs of transient peripheral pulmonary stenosis of the left pulmonary artery in association with a significant decrease of diameter at the origin of the same artery. In all 50 infants, no significant gradient was observed in the right pulmonary artery. We conclude that, at least in the preterm infant, transient peripheral pulmonary stenosis is not present at birth but is an acquired phenomenon closely related to closure of the ductus arteriosus.
Cogenital abdominal wall defects such as omphaloceles can be recognized by fetal ultrasonography. To determine whether associated anatomic features may be useful in determining fetal prognosis, a retrospective study was performed over a 5-year period. There were 28 cases of omphalocele; 16 were larger than 5 cm and classified as giant, and the remainder were considered small. Eleven of the 12 infants with small omphaloceles survived with minimal neonatal complications. Ten of the 16 infants with giant omphaloceles died because of associated congenital anomalies. These were congenital heart disease, central nervous system malformations, and diaphragmatic hernias. This review suggests that the prognosis is good when a prenatal diagnosis of giant omphalocele is made and careful fetal ultrasonography, including echocardiography, does not identify heart, central nervous system, or diaphragmatic malformations, even when there is liver herniation into the omphalocele.
This study assessed the response of the preejection period during hypoxemia with and without acidemia. In five pregnant ewes, hypoxemia was created during 1 hour followed by fetal infusion of lactic acid during 2 hours. A micromanometer catheter positioned above the fetal aortic valve, an endocavitary phonocardiogram, and a fetal electrocardiogram allowed measurements of the two components of the preejection period--the isometric contraction time and the electromechanical delay. At the onset of hypoxemia, because of changes in isometric contraction time, the preejection period began to shorten. When acidemia was induced, the preejection period modified slowly in the opposite direction and lengthened, initially because of a prolongation of electromechanical delay and later because of an increase in the already shortened isometric contraction time. This process developed slowly and at the end of 2 hours of acidemia, preejection period were back to preexperimental values. It can be concluded that systolic time intervals can be normal and misleading when acidosis complicates hypoxemia.
Eleven preterm newborn infants had a Doppler echocardiographic examination of their ventricular filling patterns during intermittent positive pressure ventilation. Peak velocity during early ventricular filling (VE) and during atrial systole (VA) and diastolic velocity-time integral of early (IE) and late (IA) ventricular filling caused by atrial contraction were measured. The ratios of VE/VA and IE/IA were also calculated. Diastolic peak velocities, as well as the diastolic velocity-time integral of early and late ventricular filling measured through the mitral valve were significantly higher during inspiration. The peak of the wave representing the velocity during atrial systole (A) was always higher than the peak of the wave representing the velocity of early ventricular filling (E). As a result, the ratio of these two variables (E/A) was always less than 1, showing no significant variation from inspiration to expiration. The flow patterns into the right ventricle were the opposite of those observed through the mitral valve. During inspiration, a significant decrease (p less than 0.001) in peak and time integral velocities of both the early ventricular filling and atrial systole waves was observed. Heart rate did not vary with respiration. It is concluded that during positive pressure ventilation, inspiration decreases right ventricular filling and enhances left ventricular filling. Opposite changes are recorded during expiration. Early and late phases of diastolic filling are equally affected. These changes are different from those observed during spontaneous breathing and should be taken into account in the assessment of diastolic ventricular function in preterm infants requiring assisted ventilation.
A study was devised to determine the P50 in infants with bronchopulmonary dysplasia (BPD). Other factors such as red blood cell 2,3-diphosphoglycerate (2,3-DPG) level proportions of adult (HbA) to fetal (HbF) hemoglobins which could affect P50 were also measured. Fourteen infants with clinical and radiological signs of BPD with a mean post-conceptional age of 42.2 +/- 4.7 weeks born at a mean gestational age of 29.3 +/- 2.0 weeks were evaluated. The percentage of HbF determined in 8 infants was 40.1 +/- 20.3% and the mean 2,3-DPG concentrations was 13.1 +/- 2.2 mumol/g Hb. The P50 was 25.1 +/- 2.7 mm Hg (range 18-29.5 mm Hg). When a HbO2 curve was established based on a large volume of blood consisting of adult blood and newborn cord blood mixed to attain a P50 of 25.1 mm Hg, the PaO2 at 90% O2 saturation was 52 mm Hg. Since there can be a wide range in HbO2 in infants with chronic BPD, pulse oximetry remains the most prudent method of monitoring oxygen therapy in BPD infants.
A study was devised to determine whether levels of fetal hemoglobin (HbF) synthesis are elevated in infants with bronchopulmonary dysplasia (BPD) when compared with the levels of HbF synthesis found in normal control infants. Twelve infants with BPD, whose postconceptional ages ranged from 40 to 62 weeks, were studied. The mean (+/- SD) gestational age and birth weight was 29 +/- 1.9 weeks and 1289 +/- 376 g, respectively. Elevation infants matched for birth weight, gestational age, and postnatal age served as the control subjects. Blood samples were incubated in an amino acid mixture containing [14C]leucine. The adult hemoglobin and HbF were then separated by column chromatography on diethylaminoethyl-Sephadex. The results demonstrated that the mean (+/- SD) level of HbF synthesis in infants with BPD was significantly higher than that in the control infants (42.6 +/- 22.9% vs 18.8 +/- 12.8%; P less than .01). When levels of HbF synthesis in the infants with BPD and the control infants were compared with data previously reported in normal infants, 7 of the 12 infants with BPD, but none of the control infants, were synthesizing amounts of HbF greater than would be expected for their postconceptional age. The results suggest that cardiopulmonary insufficiency could stimulate HbF synthesis during the first year of life as a result of an erythropoietic response to hypoxemia.
This review was undertaken to determine the effects of prenatal diagnosis, on the basis of ultrasonographic evidence, of a duodenal obstruction on the care and morbidity of the newborn infant. The records of 46 cases of either atresia or stenosis of the small bowel in infants treated during the last six years in a tertiary perinatal center were reviewed retrospectively. A prenatal fetal diagnosis of obstruction was made in 13 patients (12 obstructions located in the duodenum and one in the jejunum). The mean gestational age at prenatal diagnosis was 33.7 weeks (range 27 to 37 weeks). The course of those infants with the prenatal diagnosis made by ultrasound was compared with that of those infants in whom the diagnosis was established after the onset of symptoms of obstruction appeared. Such a prenatal diagnosis resulted in earlier surgical intervention (1.8 versus 3.9 days). Metabolic complications secondary to repeated vomiting were found to be less frequent. The expectant mother in whom such a fetal prenatal diagnosis has been made can be transported to a tertiary level perinatal center where neonatal and specialized surgical expertise are available. After birth, the infant can undergo immediate operation without being separated from its mother.
To determine whether fetal hypoxemia induced by hyperglycemia has any effect on the proportions of fetal and adult hemoglobin synthesized during fetal development, hemoglobin synthesis was determined after a period of hyperglycemic hypoxemia in the fetal lamb. These experiments were carried out at a time in gestation during the switch from fetal to adult hemoglobin. Twelve catheterized fetal sheep were included in this study. Seven were made hyperglycemic by glucose infusions during 5 days (group I) and five were control animals (group II) that received saline solution infusions (0.45 gm/dl). In group I, glycemia increased from 14.7 +/- 5.0 to 54.6 +/- 16.4 mg/dl (p less than 0.001), whereas oxygen content decreased from 8.5 +/- 1.7 to 6.4 +/- 2.2 ml/dl (p less than 0.01). Red blood cells obtained before and after 5 days of glucose or saline solution infusions were incubated in an amino acid mixture containing 14C-leucine. The hemoglobins were then subjected to polypeptide chain elution with carboxymethyl cellulose chromatography. The amount of fetal hemoglobin synthesized was determined by the ratio of radioactive gamma-chain to total of radioactive non-alpha-chains. The data demonstrated that the hyperglycemic fetus synthesizes more fetal hemoglobin than expected for the period of fetal development (78.0% +/- 10.9% versus 59.8% +/- 11.3%, p less than 0.02).