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Biomedical subjects

S Cassin

Publications and source records attributed to S Cassin.

At least 19 recordsLinked to original sources
PubMed1996

In utero lung growth of fetal sheep with diaphragmatic hernia and tracheal stenosis.

The observation that tracheal ligation produces pulmonary hyperplasia even in animals with surgically induced diaphragmatic hernia (DH) has led to rapid application of the technique to human fetuses with DH. The aim of this study was to determine how rapidly fetal lung volume increases after creation of a high-grade tracheal stenosis in fetal sheep with surgically created DH. Twenty-three fetal sheep were prepared with a left thoracotomy at 90 days' gestational. Six had creation of a DH with tracheal stenosis (DHTS) over an 18-gauge cannula, which was then removed. Ten had DH alone, and seven control animals (CT) had a thoracotomy without DH. Thirty days later, vascular and tracheal loop catheters were inserted in all animals and tunneled out the ewes' flank. Between 125 and 140 days' gestation, lung volumes and lung liquid production were measured in awake, unanesthetized animals using a standard double-marker dilution technique. Average lung volumes (in milliliters) were 150.9 +/- 13.9 for CT, 29.3 +/- 4.4 for DH, and 414.5 +/- 88 for DHTS (p < 0.01). Mean lung liquid production varied from 6.00 +/- 2.23 mL/h in DH animals before 130 days to 16.69 +/- 8.29 mL/h in DHTS animals after 135 days' gestation. DH animals had lower lung liquid production (8.51 +/- 1.4 mL/h) than CT (12.4 +/- 0.8 mL/h) or DHTS animals (12.4 +/- 2.2 mL/h)(P < .01). The rate constant gamma (h-1) for lung liquid production was significantly higher in DH animals than in either CT or DHTS animals (P < .01). Tracheal stenosis in this model causes rapid lung growth before 130 days' gestation. The authors speculate that short periods of incomplete stenosis might reverse the pulmonary hypoplasia associated with DH. To achieve this goal, the timing and duration of treatment and the optimal degree of stenosis must be defined.

Animals↗
PubMed1995

Nitric oxide administration using constant-flow ventilation.

Nitric oxide (NO) gas is known as both a vasodilator and a toxin. It can react with oxygen to form compounds more toxic than itself, such as nitrogen dioxide (NO2). The reactions are time dependent; thus, infusing NO into breathing circuits as close to ventilated subjects as possible may help minimize toxic byproduct exposure. Unfortunately, flow rates commonly used with mechanical ventilation favor laminar gas flow (streaming) within the breathing circuits. Streaming could delay mixing of NO with other inhaled gases. This mixing delay may interfere with accurate monitoring and/or delivery of NO. We tested the hypothesis that streaming of NO infused by constant flow into the inspiratory limb of a constant-flow mechanical ventilation system can lead to NO concentration delivery estimate errors. We then compared the NO2 concentrations at the ventilator Y-piece with three different NO mixing methods: blending the gases before they reach the breathing circuit inspiratory limb, infusing NO directly into the breathing circuit inspiratory limb far enough from the Y-piece to ensure thorough mixing, and infusing NO directly into the breathing circuit inspiratory limb immediately before the gases reach an in-line mixing device placed close to the Y-piece. Our results indicate that streaming can lead to NO concentration delivery estimate errors and that these errors can be characterized by measuring NO concentration variations across the inspiratory tubing's luminal diameter. NO2 concentration measured at the ventilator Y-piece were dependent on NO concentrations (p < 0.0001), NO delivery methods (p < 0.0001), and interactions between NO concentrations and NO delivery methods (p < 0.0001). We conclude that gas streaming and toxic byproduct exposure should be considered together when choosing an NO delivery method.

Dose-Response Relationship, Drug↗
PubMed1995

The effects of nitric oxide inhalation on the pulmonary circulation of preterm lambs.

This study was designed to test the hypothesis that inhalation of nitric oxide by lambs delivered prematurely would result in increased systemic arterial blood oxygen tension and decreased pulmonary vascular resistance. Eleven premature fetal lambs were delivered by cesarean section at 126-127 d gestation. One hundred min after the onset of ventilation, nitric oxide gas was added to the lambs' breathing mixture. The animals were exposed in random order to 5 ppm for 10 min, 20 ppm for 10 min, and 20 ppm for 20 min. Each treatment period was preceded by and followed by a 10-min washout period. When compared with the washout (control) periods, all three treatment periods resulted in an improvement in both the systemic arterial blood oxygen tension and the physiologic intrapulmonary shunt. Inhalation of nitric oxide also resulted in a selective decrease in pulmonary arterial blood pressure. Comparisons between the different treatment groups revealed a further improvement in blood oxygenation and pulmonary hemodynamics when using the higher concentration of nitric oxide. Interestingly, the rise in arterial blood oxygenation continued after inhaling 20 ppm nitric oxide for more than 10 min.

Administration, Inhalation↗
PubMed1994

Regulation of lung liquid secretion in immature fetal sheep: hormonal interaction.

The present studies were designed to test the hypothesis that arginine vasopressin (AVP) can interact with hydrocortisone and 3,5,3'-triiodothyronine (T3) to induce maturation of lung liquid reabsorptive processes in fetal sheep < 130 days gestation. Lung liquid production rates were measured in chronically catheterized thyroidectomized fetal sheep during eight different experimental treatments. Each experiment consisted of a 2-h control period followed by a 5-h treatment period. Net secretion or reabsorption of lung liquid was measured by using impermeant marker dilution techniques. AVP alone (50 mU/kg bolus plus 5.0 mU.kg-1.min-1 i.v. infusion) does not alter lung liquid secretion in fetal sheep 125 +/- 0.72 (SE) days gestation. In contrast, AVP (same dose as above) with T3 (30 micrograms) and hydrocortisone (6.94 mg/min) depressed lung liquid secretion and caused reabsorption of fluid. T3 alone, T3 and hydrocortisone, T3 and AVP, hydrocortisone alone, hydrocortisone and AVP, and saline did not result in net lung liquid reabsorption over a 5-h treatment period. These investigations demonstrate that AVP, T3, and hydrocortisone interact to cause lung liquid reabsorption in immature fetal lungs.

Absorption↗
PubMed1993

Amiloride inhibits arginine vasopressin-induced decrease in fetal lung liquid secretion.

The effects of arginine vasopressin (AVP) and amiloride were studied in 16 unanesthetized fetal sheep (129-135 days of age) with indwelling catheters. Secretion was measured by an impermeant tracer technique. Control fetuses showed no change in lung liquid secretion over a 5-h period with an average secretion rate of 3.6 +/- 0.31 ml.kg-1.h-1. Infusion of AVP (23.4 +/- 2.23 mU.kg-1.min-1) in seven fetuses (134-140 days of age) produced significant decreases (from control) in the secretion rate over a 5-h period: the secretion rate decreased by 68% in the last hour. Amiloride placed in the lung liquid during infusion of AVP, but after AVP effects had taken place, reversed the AVP-induced decrease in lung liquid secretion. AVP in conjunction with other hormones that are elevated during the stress of birth (epinephrine and cortisol) may be important in the removal of lung fluid at birth.

Adenylyl Cyclases↗
PubMed1992

Effects of intravenous saline infusion on fetal ovine lung liquid secretion.

These studies were designed to investigate the relationship between body fluid volume expansion and secretion of lung liquid in fetal sheep. Twelve fetal animals were used for saline infusion studies after providing them with indwelling vascular catheters and an exteriorized tracheal loop. An additional 10 animals were used as controls. Lung liquid production was measured using an impermeant tracer technique (Blue Dye Dextran). Saline infusion at 1.6, 4.0, 15.6, and 19.2 ml.kg-1.h-1 did not alter significantly lung liquid secretion rates. These results demonstrate that 1) intravenous infusion of saline at relatively high rates in the ovine fetus does not affect net fetal lung liquid formation rate, and 2) the lungs of chronically catheterized, unanesthetized fetal sheep probably do not participate in regulation of excess fluid and electrolytes.

Animals↗
PubMed1992

Endothelin-1-induced pulmonary arterial dilation is reduced by N omega-nitro-L-arginine in fetal lambs.

Endothelin-1 (ET-1) is a pulmonary vasodilator in the unventilated fetal lamb. The site and mechanism of this vasodilator response were investigated in isolated blood-perfused lungs from nine fetal lambs delivered at 127-140 days gestation. The vascular occlusion technique was used to partition the total pulmonary pressure gradient into pressure gradients across large and small arteries (delta PLA and delta PSA, respectively) and veins (delta PV). Injection of ET-1 (74 ng/kg) into the pulmonary artery significantly decreased delta PLA from 12.4 +/- 2.1 to 5.2 +/- 1.1 mmHg and delta PSA from 49.2 +/- 2.7 to 31.3 +/- 4.9 mmHg. The pressure measured by double occlusion, an estimate of pulmonary capillary pressure, was not altered by ET-1 (15.5 +/- 1.0 vs. 14.8 +/- 1.0 mmHg), indicating that ET-1 had no effect on pulmonary veins. Addition of N omega-nitro-L-arginine (estimated perfusate concentration 2-6 mM), an analogue of L-arginine that inhibits the production of endothelium-derived relaxing factor (EDRF), significantly attenuated the dilator responses to acetylcholine (10 micrograms) and ET-1 (74 ng/kg) by 35 and 56%, respectively. These results in unventilated fetal lungs indicate that 1) ET-1 dilates both large and small pulmonary arteries with no effect on pulmonary veins, and 2) this effect is mediated in part through the action of the EDRF pathway.

Acetylcholine↗
PubMed1991

Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ.

Pulmonary vascular responses to endothelin (ET-1), a peptide derived from endothelial cells in culture, were investigated in the ovine fetus delivered by cesarean section from chloralose-anesthetized ewes with intact umbilical circulation. Circulation to the lower left lobe of the fetal lung was isolated in situ and perfused at constant flow with blood withdrawn from the inferior vena cava. Injection of graded doses of ET-1 into the left pulmonary artery decreased pulmonary arterial perfusion pressure in a dose-related manner. At doses of 100, 300, and 1,000 ng, pulmonary vascular resistance per kilogram body weight (PVR/kg) was decreased 30, 40, and 42%, respectively. However, when fetuses were ventilated with 100% oxygen, 100- and 300-ng doses of ET-1 decreased PVR/kg by 5 and 9%, respectively. In contrast, injection of 1,000 ng of ET-1 resulted in a reversal of the response, and PVR/kg was increased by 70%. Ventilation of the right lung alone resulted in a similar reversal of the vasodilator response to 1,000 ng of ET-1, and a 138% increase in PVR/kg was recorded. These studies demonstrate for the first time that ET-1 has vasodilator activity in the normally high-tone ovine fetal pulmonary circulation. In addition, these results show that ET-1 has vasoconstrictor activity in the newly ventilated low-tone pulmonary vasculature. The present data indicate the pulmonary vascular responses to ET-1 are tone dependent in the ovine fetal pulmonary circulation.

Animals↗
PubMed1990

Concentration-activity profile of the modulation of cyclooxygenase product formation by reduced glutathione in microsomal fractions from the goat lung.

Age-related changes in pulmonary formation of arachidonic acid (AA) metabolites are thought to play an important role in regulating cardiopulmonary function. This study addresses the potential role of reduced glutathione (GSH) in modulating cyclooxygenase product formation in the developing lung. Prostaglandin H2 (PGH2) metabolism was studied in microsomal fractions isolated from the lungs of unventilated fetal, neonatal and adult goats. GSH-dependent PGH2 to PGE2 isomerase activity in microsomal fractions from the perinatal (fetal and neonatal) goat lung was not saturable with respect to GSH and can respond to changes in GSH concentration over the range of 0.01 to 30 mM, which encompasses the full range the intracellular GSH levels reported in the literature. However, in fractions from the adult, a lower rate of PGE2 formation is observed at higher GSH concentrations. In addition, the tissue levels of GSH exhibited developmental stage-related differences with fetal being higher than neonatal or adult. The present observations may have physiologic relevance, in that decreases in pulmonary GSH levels after birth may contribute to decreases in plasma PGE2 levels by decreasing pulmonary PGE2 synthesis, thereby contributing to closure of the ductus arteriosus; conversely, increased GSH levels associated with hyperoxia may contribute to persistence of ductal patency. Formation of 6-keto-PGF1 alpha and of TXB2 (the stable metabolites of prostacyclin and TXA2) was decreased when PGE2 formation was increased by GSH activation of PGE2 isomerase in fractions isolated from all three developmental stages. A similar pattern of product formation was observed when AA was employed as substrate. These data suggest the possibility that changes in GSH concentration may modulate eicosanoid formation in cells that contain GSH-dependent PGE2 isomerase, as well as either or both prostacyclin or thromboxane synthase(s).

6-Ketoprostaglandin F1 alpha↗
PubMed1990

The role of lung perfusate PO2 in the control of the pulmonary vascular resistance of exteriorized fetal lambs.

The isolated perfused lower left lung lobe of the exteriorized fetal lamb was used to define quantitatively the relationship between pulmonary perfusate oxygen tension and pulmonary vascular resistance (PVR) in the fetus at multiple oxygen tensions over the range from 8.3 to 433 mm Hg. This allowed variation of the perfusate PO2 over the range of partial pressures from less than 10 mm Hg to over 400 mm Hg while constant values of PCO2, temperature and perfusate flow were maintained. In all animals, calculated pulmonary vascular resistance varied in an inverse manner with the perfusate PO2. The relationship between PVR and perfusate oxygen tension is described by the equation: PVR = 7.67 - 1.54 (log PO2) R2 = 0.70. While others have shown that a single, large increase in blood oxygen tension will decrease the PVR in fetal lambs, these data present the first quantitative description of the role of oxygen tension in the modulation of fetal pulmonary vascular resistance as determined at multiple perfusate oxygen tensions over a fifty-fold range.

Animals↗
PubMed1990

Leukotrienes and prostaglandins in fetal lung liquid.

Several recent studies have suggested that peptidoleukotrienes are involved in or responsible for the pulmonary pressor response to hypoxia as well as the normally high pulmonary vascular resistance of fetal lambs. The present studies were carried out to test these hypotheses. Fetal lambs were prepared with indwelling vascular catheters and tracheal catheters for access to lung liquid. We measured lung liquid levels of leukotrienes C4 (LTC4) and D4 (LTD4) in control unanesthetized fetal lambs with blood gases and pH in the normal range. In the control series, LTC4 and LTD4 were either not detectable or their levels were close to the limit of resolution (LTC4, less than 80 pg/ml; LTD4, less than 50 pg/ml) of the techniques utilized. Leukotriene E4 was measured in a separate study by using pooled samples, and it was also found to be below the detection limit of that assay (10 pg/ml). In a second series of animals, a level of acute hypoxia was induced to decrease fetal arterial PO2 to 12 Torr for 20 min. After hypoxia, tracheal fluid levels of leukotrienes were again below detection limits of the assays used (LTC4, less than 80 pg/ml; LTD4, less than 142 pg/ml). In another study, methodology was altered to lower the detection limits of leukotrienes in lung fluid and to allow the measurement of total peptidoleukotriene concentrations. In this study, even when hypoxia was extended for up to 1 h, leukotriene levels were consistently below the limit of detection of the assay (less than 20 pg/ml for the sum of all leukotrienes).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1989

The effects of arginine vasopressin and epinephrine on lung liquid production in fetal goats.

The effects of arginine vasopressin (AVP) and epinephrine on lung liquid secretion were investigated in 67 acute fetal goats (116 days of gestation to term) with intact umbilical cords after caesarean section. Secretion was measured by an impermeant tracer technique. AVP was infused intravenously (1.6-39.2 mU/(kg.min); 2 h) into 26 fetuses. All fetuses below 130 days of gestation, except one, showed no response. All above 133 days reduced secretion, or turned to reabsorption, except at the lowest infusion rate. The effect persisted, and usually increased postinfusion. Expansion of the lungs with saline did not change the response. The percentage reductions were linearly related to the logarithm of the infusion rate (threshold, 1.42 mU/(kg.min]. The absolute reductions were linearly related to fetal weight. Epinephrine was infused intravenously (0.30-6.72 micrograms/(kg.min); 1-2 h) into 12 fetuses. All fetuses (118 days to term) reduced secretion or reabsorbed by the second hour. At the highest infusion rate, reabsorption was immediate; at the lowest, secretion increased slightly, then fell significantly in the second hour. Epinephrine acted at levels considered physiological at delivery in the sheep. AVP appears to act at plasma levels found in most vaginal deliveries; it may augment epinephrine-induced reabsorption during stress, and help long-term removal of lung fluid.

Animals↗
PubMed1989

Do inhibitors of lipoxygenase and cyclooxygenase block neonatal hypoxic pulmonary vasoconstriction?

Lipoxygenase products have been suggested as mediators of the hypoxic pulmonary pressor response in newborn animals. Data supporting this suggestion are equivocal, since lipoxygenase and leukotriene receptor antagonists that have been used may produce vasodilation because of phosphodiesterase inhibition. We used a leukotriene receptor antagonist L 649923, which appears not to have smooth muscle relaxant activity. L 649923 blocks pressor responses to leukotriene D4 (LTD4) without diminishing the pressor response to hypoxia. Also, BW 755C did not block the pressor response to hypoxia in newborn sheep and goats, whereas the pressor response to LTD4 (75 ng/kg) was depressed significantly. In newborn sheep there was an augmented response to hypoxia with BW 755C, which is consistent with cyclooxygenase inhibition. Finally, the thromboxane receptor antagonist SQ 29548 was investigated in both species. With this agent the pressor response to LTD4 in contrast to that of hypoxia was completely inhibited. We conclude that thromboxanes are involved in the pressor response to LTD4 in newborn lambs and goats. These data do not support the view that leukotrienes are involved in the ovine or caprine neonatal pulmonary pressor response to hypoxia.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1989

Ethanol induces acute pulmonary vasoconstriction in salt-perfused rat lungs.

Ethanol is a pulmonary vasoconstrictor in rat lungs perfused in situ with Krebs-Henseleit salt solution. Pentobarbital-anesthetized rats were tracheotomized, and an in situ recirculating isolated lung perfusion was instituted using a Krebs-Henseleit buffer with 3% bovine albumin at 37 degrees C. Changes in pulmonary arterial pressure and tracheal inspiratory pressure during intravenous ethanol infusion at four different cumulative doses were measured in normoxic (n = 6) and hyperoxic (n = 6) lungs, compared to normoxic perfusate (no ethanol infusion) controls (n = 6). Perfusate alcohol levels progressively increased in experimental groups. Perfusate gas and pH values were normal and not altered by ethanol. PAP increased by the end of ethanol infusion from 9.7 +/- 2 to 26 +/- 13 mm Hg in the normoxic group and from 10.6 to 22 +/- 9 mm Hg in the hyperoxic lungs (p less than .02); no change occurred in control lungs. Severe pulmonary edema occurred in 83% of the ethanol exposed lungs (vs. 0% of perfusate controls). Postethanol wet/dry weight ratios were twice normal (p less than .02). Pulmonary arterial pressure rose in two stages. First there was a 25-100% increase before airway pressure increased, representing pulmonary vasoconstriction. This was followed by a precipitous 100-500% transmitted pressure rise as severe pulmonary edema developed. Thus, we conclude that the vasoconstrictor effect of ethanol on the pulmonary circulation occurs in rats as well as in lambs, dogs, and humans. In isolated perfused rat lungs, the response is locally mediated.

Animals↗
PubMed1988

Carboxy- and oxyhemoglobin in pregnant ewe and fetus after inhalation of marijuana, marijuana placebo and tobacco cigarette smoke.

We measured carboxyhemoglobin (HbCO) and oxyhemoglobin (HbO2) percent saturations and blood gases in four near-term pregnant ewes and their fetuses, during and for 6 hours after 9-12 minutes of smoke inhalation from one high-potency marijuana cigarette (M), a marijuana placebo cigarette (P), and a reference tobacco cigarette (T). Maternal HbCO reached maximum levels at or soon after the exposure (M, 2.8%; P, 3.5%; T, 6.3% above baseline) and fell to baseline values by 6 hours. Fetal HbCO rose slowly reaching a plateau at 3 hours (M, 0.7%; P, 1.1%; T, 2.0% above baseline) which was maintained for at least three additional hours. Reductions in maternal and fetal HbO2 after exposure to marijuana placebo and reference tobacco cigarettes reflected these rises in HbCO. After exposure to marijuana cigarettes, however, fetal HbO2 dropped precipitously by 17% of baseline and showed a prolonged rate of return to presmoking HbO2 levels. Although P exposure caused a greater change in HbCO in the fetus than did M, it had a less-profound effect on fetal oxygenation.

Animals↗
PubMed1988

Specificity of FPL 57231 for leukotriene D4 receptors in fetal pulmonary circulation.

The effects of leukotriene D4 and the putative leukotriene receptor antagonist FPL 57231 were studied on the pulmonary circulation of alpha-chloralose-anesthetized fetal lambs close to term. At constant pulmonary inflow leukotriene D4 (LTD4, 0.1-10 micrograms), as bolus injections, caused dose-dependent increases in pulmonary vascular resistance. FPL 57231 (1.0-10 mg/kg) not only blocked the pressor responses to LTD4 but also lowered the normal pulmonary vascular resistance in a dose-dependent fashion. However, FPL 57231 also decreased the pulmonary pressor response to U 46619, a thromboxane A2 mimic, as well as the pressor response to phenylephrine HCl. Furthermore, the pressor responses to LTD4 were markedly reduced by cyclooxygenase inhibition. In preliminary experiments we demonstrated that the phenidone derivative, BW755C, which is a dual inhibitor of both cyclooxygenase and 5-lipoxygenase enzymes, did not block the pressor response to hypoxia. We conclude that FPL 57231 decreases fetal pulmonary vascular resistance by nonspecific mechanisms. Also the action of LTD4, is indirect and by way of the cyclooxygenase system. Although exogenous leukotrienes are able to produce a marked pulmonary pressor response, endogenous leukotrienes are probably not responsible for the hypoxic pulmonary pressor response of the fetal lung or its normally high pulmonary vascular resistance.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗