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Biomedical subjects

C Roman

Publications and source records attributed to C Roman.

At least 73 records · Page 4Linked to original sources
PubMed1987

Structure-activity relationships (SAR) of the 3-alkyl substituents among a series of hydroxy-acetophenone leukotriene antagonists.

LY171883 is an orally active antagonist of leukotriene (LT) D4 and LTE4. A series of related compounds varying the position and nature of the alkyl side chain were synthesized and evaluated for their ability to block LTD4-induced contraction of guinea pig ileum. Maximal activity was obtained with n-propyl, n-butyl, and n-pentyl substituents with slightly reduced activity for longer side chains. Polar groups on the side chain substantially reduced activity. Thus, it appears that the leukotriene receptor site requires a nonpolar alkyl group of moderate size at the 3-position on this type of receptor antagonist.

Acetophenones↗
PubMed1987

Cardiovascular effects of patent ductus arteriosus in preterm lambs with respiratory distress.

We created a model for studying the cardiovascular and pulmonary effects of patent ductus arteriosus (PDA) in premature lambs with respiratory distress. In 47 fetal lambs at 129 to 133 days gestation (term, 145 days), we infiltrated the ductus arteriosus with formalin and placed a mechanical occluder about it so that its patency could be regulated. Two days later the lambs were delivered, given sheep surfactant, paralyzed, and their lungs mechanically ventilated. These premature lambs could more than double their left ventricular output when challenged with increasing degrees of left-to-right shunts through the PDA. This was accomplished by an increase in stroke volume, not by an increase in heart rate. During the 40-minute observation period, there was no change in dynamic compliance or functional residual capacity while the ductus was patent. When the ductus was patent, there was a significant increase in arterial PaO2 (even with small left-to-right shunts) and a decrease in PaCO2 (with large shunts). Despite the heart's ability to handle the increased volume load of a PDA, there were significant alterations in individual organ blood flows, resulting from a combination of decreased perfusion pressure and localized vasoconstriction. The abdominal organs had significant reductions in blood flow even with small PDA shunts. This decrease in organ blood flow may explain some of the pathophysiologic manifestations of PDA in preterm infants.

Animals↗
PubMed1987

Harlequin foetus in four siblings.

Four siblings (three males, one female), affected by harlequin foetus, are presented. Genetic aspects and classification of this variety of ichthyosis are discussed.

Diseases in Twins↗
PubMed1987

Respiratory effects of a patent ductus arteriosus in premature newborn lambs.

We examined the respiratory effects of a patent ductus arteriosus in 29 premature lambs (131-135 days gestational age) after infiltrating the ductal wall with formaldehyde solution (Formalin) and placing a snare around the ductus to regulate its patency. The lambs were given sheep surfactant, paralyzed, and mechanically ventilated at birth. We first compared 8 lambs with open ductus and 13 lambs with closed ductus during the 12 h after birth. Although lambs with open ductus had greater pulmonary blood flow (301 +/- 36 vs. 188 +/- 11 ml.min-1.kg-1, mean +/- SE, at 12 h of age) and mean pulmonary arterial (44 +/- 3 vs. 33 +/- 2 mmHg) and left ventricular end-diastolic (6 +/- 0.6 vs 4 +/- 0.7 mmHg) pressures, we found no differences in dynamic respiratory compliance (Cdyn = 0.55 +/- 0.07 vs. 0.55 +/- 0.03 ml.cmH2O-1.kg-1), midtidal volume resistance (62 +/- 5 X 10(-3) vs. 62 +/- 7 X 10(-3) cmH2O.ml-1.s), or functional residual capacity (FRC = 27 +/- 3 vs. 26 +/- 2 ml.kg-1). Alveolar-arterial PO2 difference was lower in the lambs with open ductus (238 +/- 65 vs. 362 +/- 37 Torr). Next, we challenged eight lambs with two separate saline infusions (50 ml.kg-1 over 3 min), each given with the ductus alternately closed or open. When the ductus was closed, FRC was unchanged, but Cdyn increased by 18% immediately after the infusion. When the ductus was open, FRC decreased by 16% and Cdyn decreased by 12%. We conclude that the premature lamb is surprisingly resistant to changes in respiratory function from ductal patency during the immediate neonatal period.

Animals↗
PubMed1987

How a patent ductus arteriosus effects the premature lamb's ability to handle additional volume loads.

A model of patent ductus arteriosus in premature lambs was created to examine the lamb's ability to handle the volume load imposed by a patent ductus arteriosus and to determine the lamb's ability to handle any additional volume load. Fifteen preterm lambs [133 +/- 2 (+/- SD) days gestation, term 145 days], whose ductal diameter could be regulated with a mechanical occluder, were studied to determine the independent effects of ductus patency and a saline volume load (50 ml/kg over 3 min) on left ventricular output and its distribution. During a saline infusion, preterm lambs with a closed ductus could only increase their stroke volume by 40% above baseline stroke volume. When challenged with a saline infusion, lambs with an open ductus still were able to increase their stroke volume significantly; the maximal increase in stroke volume during the saline load with the ductus open was 70% above baseline stroke volume. We hypothesize that the associated reduced left ventricular afterload plays a significant role in the preterm lamb's ability to increase its stroke volume when challenged with a patent ductus arteriosus. Even with a patent ductus arteriosus, the lamb still has the ability to handle additional volume loads.

Animals↗
PubMed1987

Umbilical cord compression produces pulmonary hypertension in newborn lambs: a model to study the pathophysiology of persistent pulmonary hypertension in the newborn.

We investigated the effects of chronic intrauterine hypoxaemia produced by prolonged partial umbilical cord compression on the circulation shortly after birth in lambs. Vascular catheters were inserted in 10 fetal sheep at 120 to 130 days gestation to measure descending aortic blood gases, arterial pH, and arterial O2 saturation. An inflatable silicone rubber balloon cuff was also placed around the umbilical cord. After recovery and the return of descending aortic blood gases to the normal range, the balloon was gradually inflated, decreasing the PaO2 from 21.2 +/- 3.6 to 17.5 +/- 1.3 mm Hg and the arterial O2 saturation from 57.1 +/- 9.2% to 37.2% +/- 5.2. After 14.3 +/- 3.7 days of partial umbilical cord compression, the lambs were delivered by Caesarean section, instrumented to measure systemic and pulmonary arterial, right atrial and pulmonary arterial wedge pressures, pulmonary and systemic blood flows, and mechanically ventilated. Five normal lambs were also studied. From 60 to 120 min after delivery, when compared to normal lambs, the umbilical compression lambs had an increased pulmonary arterial pressure (P less than 0.05) pulmonary vascular resistance (P less than 0.05), and right atrial pressure (P less than 0.05) with similar arterial blood gases. In both groups, hypoxic ventilation produced an increase in pulmonary arterial pressure (P less than 0.05) which on return to room air ventilation decreased to baseline in the normal lambs but not in the umbilical cord compression lambs (P less than 0.05). Prolonged partial umbilical cord compression produces chronic fetal hypoxaemia and pulmonary arterial hypertension after birth. This may represent a model to study the pathophysiology of persistent pulmonary hypertension syndrome.

Animals↗
PubMed1986

[Neural control of deglutition and esophageal motility in mammals].

Swallowing is a complex motor sequence involving the coordinated contraction of many muscles of the buccopharyngeal cavity, the larynx and the oesophagus. Most of the muscles are striated except those of the distal oesophagus which, in human and some other species, are of the smooth type. During swallowing, usually divided into a buccopharyngeal and an oesophageal stage (peristalsis), the sequential activity of the muscles results from motor orders programmed by a rhombencephalic swallowing centre and conveyed to the periphery by efferent fibres belonging to various pairs of cranial nerves (Vth, VIIth, IXth, Xth). Apart from the motor nuclei of the cranial nerves, the swallowing centre contains an nuclei of the cranial nerves, the swallowing centre contains an interneurone network responsible for the programming of deglutition. During swallowing, these interneurones (INs) exhibit a sequential activity quite parallel to that of muscles, and persisting in the absence of sensory feedback. The "swallowing INs" are located in two medullary regions: a dorsal region including the nucleus of the solitary tract and the adjacent reticular formation, a ventral region corresponding to the reticular formation surrounding the nucleus ambigus. The dorsal INs are involved in the initiation and the programming of swallowing. The ventral INs receive their swallowing input from the dorsal neurones and are probably switching neurones that distribute the swallowing excitation to the various pools of motoneurones. The swallowing program can be triggered by inputs originating from either the peripheral reflexogenic areas or the supramedullary structures (cerebral cortex in particular). Under physiological circumstances, the swallowing program is continuously modified by peripheral afferents (especially muscular) that adjust the force and the timing of contractions to the size of the swallowed bolus. In addition, an important operating feature of the programming network consists of a functional polarization so that the activity of proximal portions of the swallowing tract inhibits that of distal portions. This polarization implies the existence of inhibitory connections between interneurones, that could constitute "time-lag lines" responsible for the series of delays typical of the swallowing contractile sequence. Lastly, although the smooth muscle oesophagus contains its own programming system (intramural nervous system), motility of this area during deglutition also depends on the medullary program that combines with the intramural program by ways not yet elucidated.

Animals↗
PubMed1985

Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs.

The factors responsible for maintaining the normally low pulmonary blood flow and high pulmonary vascular resistance in the fetus are not well understood. Since leukotrienes are potent pulmonary vasoconstrictors in many adult animal species, we determined whether leukotrienes were perhaps involved in the control of the fetal pulmonary circulation by studying the effects of putative leukotriene end organ antagonists in two groups of fetal lambs. In six fetal lambs studied at 130-134 days gestation, FPL 55712 increased pulmonary blood flow by 61% (P less than 0.05) and reduced pulmonary vascular resistance by 45% (P less than 0.05). There was a small increase in heart rate but no changes in pulmonary and systemic arterial pressures and systemic arterial blood gases. In six other fetal lambs studied at 130-140 days gestation, FPL 57231 increased pulmonary blood flow by 580% (P less than 0.05) and decreased pulmonary vascular resistance by 87% (P less than 0.05). Pulmonary and systemic arterial pressures decreased (P less than 0.05), and heart rate increased (P less than 0.05). Leukotriene end organ antagonism significantly increases fetal pulmonary blood flow and decreases pulmonary vascular resistance. Leukotrienes may play a role in the physiological control of the fetal pulmonary circulation.

Animals↗
PubMed1985

Hepatic oxygen consumption, lactate uptake, and glucose production in neonatal lambs.

Previous studies have evaluated neonatal hepatic metabolism in vitro, and neonatal hepatic oxygen consumption has been measured in vivo, but direct measurements of neonatal hepatic metabolism have not been reported. We studied seven neonatal lambs at age 7-10 days after placing catheters chronically in the hepatic vein, portal vein, descending aorta, left ventricle, and inferior vena cava. Hepatic blood flow was measured by the radioactive microsphere technique. Oxygen consumption and glucose and lactate fluxes were measured using the Fick principle. 14C-lactate was infused intravenously and lactate and glucose specific activities were measured and used to calculate hepatic gluconeogenesis from lactate. Neonatal hepatic blood flow was 254.5 +/- 50.3 ml/min/100 g (mean +/- SD) with 5.4 +/- 4.6% from the hepatic artery and 94.6 +/- 4.6% from the portal vein. Hepatic oxygen consumption was 7.2 +/- 2.4 ml/min/100 g and oxygen extraction was 44.9 +/- 15.4%. Oxygen extraction correlated inversely with oxygen delivery. In the seven lambs, there was net hepatic lactate uptake of 10.2 +/- 5.0 mg/min/100 g (1.13 +/- 0.56 mM) and hepatic glucose production of 30.8 +/- 11.3 mg/min/100 g (1.71 +/- 0.62 mM). In the five lambs in which hepatic gluconeogenesis was measured, 12.4 +/- 5 mg (1.37 +/- 0.56 mM) of lactate was converted to glucose per 100 g liver, accounting for 38.4% of the hepatic glucose production in these lambs. Blood flow and oxygen and substrate delivery to the neonatal liver are lower than those to the fetal liver but the neonatal liver extracts more oxygen and substrates and is able to produce glucose by gluconeogenesis from lactate.

Animals↗
PubMed1984

Effects of fetal-maternal exchange transfusion on fetal oxygenation and blood flow distribution.

The effect of reducing hemoglobin affinity for O2 on fetal oxygenation was assessed in seven fetal lambs in which fetal blood was almost completely replaced by maternal blood 2-3 days postoperatively. Measurements of fetal blood gases and organ blood flow (radionuclide-labeled microsphere technique) were obtained before and 1 h after the exchange transfusion. Umbilical venous blood PO2 increased from 29 +/- 5 to 35 +/- 6 (SD) Torr (P less than 0.001) but hemoglobin O2 saturation decreased from 78.2 +/- 10.3 to 39.8 +/- 8.8% (P less than 0.001), resulting in a 46% decrease in umbilical venous blood O2 content. Since umbilical-placental blood flow also decreased (P less than 0.002), O2 delivery to the fetus decreased by 64% (P less than 0.002). Although O2 extraction increased from 32.5 +/- 6.8 to 50.9 +/- 9.0% (P less than 0.002), fetal O2 consumption fell from 7.28 +/- 1.97 to 4.10 +/- 1.20 ml X min-1 X kg-1 (P less than 0.02), and metabolic acidemia developed. No significant change in fetal cardiac output was observed. Blood flow increased significantly to the myocardium and adrenals but fell in the placenta, carcass, and lungs and was maintained in other organs. This resulted in a significant decrease in the amount of O2 delivered to all fetal organs except to the myocardium in which it was maintained. In the sheep the higher affinity of fetal blood hemoglobin for O2 helps maintain normal oxygenation during fetal life by facilitating O2 uptake at the placenta and unloading O2 in the tissues.

Animals↗
PubMed1983

Effect of gestational age on ductus arteriosus response to circulating prostaglandin E2.

Premature newborn lambs with a patent ductus arteriosus have higher plasma prostaglandin E2 concentrations than near-term newborn lambs with a contricted ductus arteriosus. To see whether these concentrations of PGE2 could produce patency of the ductus arteriosus, we studied eight near-term lambs (with constricted ductuses) delivered by cesarean section, paralyzed, and mechanically ventilated. After ductus arteriosus resistance and plasma PGE2 concentrations had stabilized, a continuous PGE2 infusion into the superior vena cava was started to determine threshold concentrations needed to dilate the ductus in vivo. By two hours after birth, circulating PGE2 concentrations in near-term lambs were considerably less then the threshold concentration, and the ductuses were constricted. In five premature newborn lambs, significantly lower concentrations of PGE2 were required to dilate the ductus: threshold and ED50 concentrations were one sixth and one third, respectively. In these premature lambs during the first two hours after birth, circulating PGE2 concentrations were twice as high as the calculated in vivo threshold level. Therefore, circulating PGE2 concentrations probably played a significant role in the patency of the ductus arteriosus in these premature lambs.

Animals↗
PubMed1983

Factors determining the loss of ductus arteriosus responsiveness to prostaglandin E.

The ductus arteriosus of the newborn infant varies in its ability to dilate when doses of prostaglandin E (PGE) are administered. We infused PGE2 into 15 late-gestation newborn lambs to determine which factors regulate the ability of the ductus arteriosus to respond to PGE. PGE2 dilated the ductus in 10 lambs (responders); in five other lambs, despite similar PGE2 concentrations, there was no effect (nonresponders). The measured ductus resistance after the PGE2 infusion was directly related to the ductus resistance before the infusion. Responders had a larger left-to-right shunt through the ductus before the PGE infusion than nonresponders. Ductus that were isolated and studied in vitro from lambs that were nonresponsive to PGE2 (in vivo) were limited in their ability to relax with PGE2 as well as to actively contract with oxygen and indomethacin. This generalized loss of ductus responsiveness was directly related to the amount of the left-to-right shunt through the lumen of the ductus. These observations are consistent with the hypothesis that the constriction of the ductus arteriosus after birth limits the ability of the ductus to respond to PGE therapy.

Animals↗
PubMed1982

Increased shunt through the patent ductus arteriosus after surfactant replacement therapy.

Instillation of surfactant into the trachea of preterm infants with respiratory distress syndrome is associated with a 90% incidence of patent ductus arteriosus. We studied the effects of surfactant therapy on the ductus arteriosus in 12 preterm lambs. Flow across the ductus arteriosus and systemic blood flow were calculated from radioactive microsphere injections. All developed respiratory failure (pH less than 7.1, Paco2 greater than 60) by 30 minutes after birth. Between 30 and 60 minutes after birth, six lambs were treated with tracheal instillation of 50 mg/kg surfactant lipid. By two hours after birth, treated lambs differed significantly from controls in pH (7.27 +0.02 vs 6.97 +0.08) and Paco2 (43.3 +4.1 vs 85 + 15). There were no differences in Pao2 or PGE2 concentrations or ductus arteriosus resistance, but there was a significantly larger shunt through the ductus arteriosus in treated lambs. This increased shunt resulted from the significant drop in pulmonary vascular resistance and not from a change in patency of the ductus arteriosus. Surfactant replacement may require interventions directed specifically at the patent ductus arteriosus in sick preterm infants.

Animals↗
PubMed1981

Effect of gestational age on pulmonary metabolism of prostaglandin E1 & E2.

The fetus and prematurely delivered newborn lamb have high concentrations of circulating PGE2 that may play a hormonal role, particularly in maintaining the patency of the ductus arteriosus. We studied the ability of the isolated, perfused lung from immature (100 +/- 2 days gestation, +/- SEM n = 8) and near term (142 +/- 1 days, n = 10; term is 150 days) lamb fetuses to metabolize PGE2 as a function of PGE2 concentration in the perfusate. After an intra-arterial infusion of 3H-PGE2 and 14C-inulin (to act as a marker of extracellular space), the bulk of the 14C-inulin was rapidly cleared through the isolated lung and the majority of the 3H activity appeared after the 14C activity had fallen to negligible values. The 3H activity that was retained longer in the lung was primarily associated with the 15-keto prostaglandin E2 and 15-keto-13,14 dihydro prostaglandin E2 metabolites. Lungs from immature fetal lambs metabolized 25% less PGE2 than did lungs from animals near term. This is consistent with our prior observation that premature lambs have decreased plasma clearance rates (in vivo) and elevated circulating concentrations of PGE2 when compared with term newborn lambs.

Alprostadil↗