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Biomedical subjects

S Cassin

Publications and source records attributed to S Cassin.

At least 55 records · Page 3Linked to original sources
PubMed1982

Preparation and stability of indomethacin solutions.

Indomethacin is used in closure of the ductus arteriosus in newborn humans as well as in related research in near-term sheep and goats. Conflicting data in these studies have led to a reexamination of indomethacin stability. Solutions at various pH values, at two temperatures, and in polyethylene glycol (PEG-400), were assessed by high-pressure liquid chromatography for indomethacin and its products. Solutions below pH 7.4 were stable. Decomposition was rapid in alkaline solutions. Solutions at pH 7.4 showed no changes up to 24 h. Solutions of sodium indomethacin, and of indomethacin in PEG were stable. Solutions in aqueous Na2CO3 were variably stable depending on the mode of mixing. A solution prepared directly in 0.1 M Na2CO3 (pH 10.7) lost 75% of its content in 80 min; a similar solution diluted immediately with two volumes of pH 7.4 buffer (final pH 9.9) showed less decomposition. A solution in Na2CO3 adjusted to pH 7.4 with HCl was stable (at least 24 h). Solutions prepared by suspending indomethacin in 0.9% NaCl and adding Na2CO3 slowly were stable for 80 min; rapid mixing led to decomposition. Solutions in plasma were stable at -20 degrees C (2 months). Lack of indomethacin activity in some biological studies may have resulted from injection of inactive solutions.

Drug Stability↗
PubMed1982

Studies of factors which stimulate lung fluid secretion in fetal goats.

Twenty near-term fetal goats, delivered by Caesarian section, under chloralose (50 mg/kg), with intact umbilical cords, were monitored for lung fluid production by a dye dilution method. Controls, and fetuses given slow infusions of saline (0.9% (w/v) NaCl at 0.028 - 0.042 ml/kg per min, intravenous, for 2 h), showed no significant increases in lung fluid production, Na+ secretion, or Na+ concentration in lung fluid. Intermediate rates of infusion (0.053 ml/kg per min for 2 h) did not increase fluid production, but significantly increased Na+ secretion and Na+ concentration in lung fluid. Fast infusions (0.084 - 0.24 ml/kg per min for 2-3 h) increased significantly fluid secretion (up to 40-fold), Na+ secretion (up to 9.3-fold), and Na+ concentration in lung fluid (increases up to 5.2 mequivalents/l); in one case, spontaneous reabsorption was reversed to secretion. Prolactin, placed directly in the lungs (10 micrograms/ml fluid), by the third hour; controls showed no changed. In all cases Cl- behaved similarly to Na+; K+ moved partly independently. Synthetic pentagastrin (infused at 0.12-2.5 micrograms/kg per min, intravenous) did not stimulate secretion. The results suggest that the fetal lungs may influence salt-water balance, and this may be under prolactin control.

Animals↗
PubMed1981

Effects of prostaglandin D2 on perinatal circulation.

Prostaglandin D2 (PGD2) is a powerful antiaggregatory agent and contracts various types of smooth muscle preparations, including isolated canine and bovine pulmonary vessels. Pulmonary vascular responses of anesthetized fetal and adult goats and newborn lambs to PGD2 were evaluated in situ by means of an isolated perfused lower left lobe preparation. These experiments indicate that PGD2 is a pulmonary vasodilator in fetal goats, both a pulmonary vasodilator and vasoconstrictor in newborn lambs depending on the dose used, and a pulmonary vasoconstrictor in adult goats. Evidence is presented of an age-related change in pulmonary vascular response to prostaglandins. The responses of the pulmonary vasculature are dose dependent; however, there is not a significant dose-dependent relationship for systemic arterial pressure or heart rate with intrapulmonary infusions of PGD2. The inhibition of prostaglandin synthesis potentiates the pulmonary response to PGD2 in fetal goats. In contrast with other prostaglandins, PGI2, PGE2, and PGE1, which dilate both the fetal pulmonary and systemic circulations, PGD2 has minimal action on the systemic circulation over a wide range of doses.

Aging↗
PubMed1981

New thermal method for evaluating vaginal blood flow.

The goal of this study was the development noninvasive technique for measurement of vaginal blood flow. A vaginal probe (diameter 1.84 cm; length 7.0 cm) was constructed by winding 23 m of 34-gauge enameled copper wire around a hollow cylinder of epoxy-impregnated glass wool. Resistance of the wire was 20 omega at 40 degrees C. Surface area of coil was 40.5 cm2. The temperature of the wire midway along the coil was measured continuously with a thermcouple. Temperature difference (delta T) between coil and vagina was raised by delivery of 300 mA with a resultant production of 1.8 W. In ewes treated with 1 mg estrone im., delta T fell significantly (p less than 0.025) by 90 min and (p less than 0.005) by 120 min after injection. There was a significant correlation between delta T and vaginal blood flow as measured by the radiolabeled microsphere technique.

Animals↗
PubMed1981

Effects of prostacyclin on the fetal pulmonary circulation.

The effects of prostacyclin (PGI2) and its metabolite, 6-keto-PGF1 alpha, on pulmonary and systemic circulations of anesthetized, unventilated fetal goats and sheep were evaluated in situ using an isolated perfused lower left lobe preparation. Results from infusions of PGI2 into the left pulmonary artery suggested dose-dependent decreases in pulmonary vascular resistance (PVR) and mean systemic arterial pressure (SAP). Two-minute infusions produced more pronounced reductions in PVR than 1-minute infusions, and fetal goats exhibited greater depressor responses to PGI2 (2-minute infusions) than fetal lambs. For every 10% decrease in mean pulmonary arterial pressure (PAP), SAP decreased by 3% in sheep receiving 1-minute infusions of PGI2. Systemic hypotensive responses and increases in heart rate were similar in both species. PGI2 appears to be a more powerful dilator of the fetal pulmonary circulation than PGE1 or PGE2; also, intrapulmonary infusions of PGI2 resulted in greater and more sustained systemic hypotensive effects than similar infusions of PGE1 and PGE2. The stable metabolite of PGI2, 6-keto-PGF1 alpha, produced attenuated pulmonary vasodilation. Since PGI2 may produce systemic hypotension, the use of this agent in treatment of persistent pulmonary hypertension should be considered with caution.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Comparative effects of PGD2 and PGE2 on vasoconstrictor responses in the feline intestinal vascular bed.

The effects of prostaglandins (PG) D2 and E2 on vascular resistance and vasoconstrictor responses were compared in the feline mesenteric vascular bed under conditions of controlled flow so that changes in perfusion pressure directly reflect changes in vascular resistance. Infusions of PGD2 into the superior mesenteric artery significantly dilated the mesenteric vascular bed and inhibited vasoconstrictor responses to sympathetic nerve stimulation and intra-arterial injections of norepinephrine and angiotensin II. The inhibitory effects of PGD2 were reversible and dose-dependent. PGD2 inhibited responses to sympathetic nerve stimulation to a greater extent than responses to the pressor hormones. Infusion of PGE2 at similar doses dilated the mesenteric vascular bed but had little or no effect on vasoconstrictor responses to sympathetic nerve stimulation or pressor hormones. These data suggest that PGD2 possesses the ability to modulate responses to nerve stimulation and pressor hormones by both pre- and post-junctional actions in the feline mesenteric vascular bed.

Angiotensin II↗
PubMed1979

Pulmonary and systemic vascular responses of perinatal goats to prostaglandins E1 and E2.

Effects of prostaglandins of the E series and their metabolites on pulmonary and systemic circulations of newborn and exteriorized fetal goats (anesthetized with chloralose) were evaluated in situ using an isolated perfused left lung lobe preparation. Prostaglandin E1 (PGE1) and, to a lesser extent, prostaglandin E2 (PGE2) infusions resulted in decreases of pulmonary vascular resistance (PVR) of fetal and neonatal goats. Infusions of PGE1 or PGE2 (less than 2 microgram.kg-1.min-1 for 1 min) directly into left pulmonary arterial blood did not affect systemic arterial pressure (SAP). Infusions of PGEs (greater than 2 microgram.kg-1.min-1 for 1 min) resulted in decreases in SAP and heart rate. The dose-response characteristics of the pulmonary circulation in response to PGE1 and PGE2 were not different in fetal and newborn goats. Fetal asphyxia did not alter the dose-response characteristics of pulmonary circulation in response to PGE1. Metabolites (15-keto) of PGE1 and PGE2 had no effect upon PVR or SAP of perinatal goats. These results demonstrate in perinatal mammals 1) vasodilator action of PGE1 and PGE2 on the pulmonary and systemic circulations, and 2) catabolism by the lungs of these prostaglandins.

Animals↗
PubMed1978

Sodium transport by isolated bullfrog small intestine. Effect of prostaglandin E1.

Addition of 446 micron prostaglandin E1 (PGE1) to the serosal medium of isolated short-circuited bullfrog small intestine elicited small increases transmural potential difference and short-circuit current while addition of PGE1 to the mucosal medium caused no change in the electrical parameters. Addition of 100 micron indomethacin to the mucosal medium inhibited both potential difference and short-circuit current with a resultant increase in steady-state tissue resistance. In the presence of mucosal 100 micron indomethacin, serosal 60 micron PGE1 markedly stimulated transmural potential difference and short-circuit current with a resultant decrease in steady-state tissue resistance. Serosal arachidonic acid (330 micron) stimulated transmural potential difference and short-circuit current and this effect was abolished by the addition of 100 micron indomethacin to the mucosal medium. Serosal 60 micron PGE1 only stimulated the M (mucosa) leads to S (serosa) unidirectional flux of sodium. These results strongly suggest that the PGE1 action is mediated either via a series of metabolic reactions which possibly increase the permeability of the mucosal membrane to sodium or via direct stimulation of rheogenic sodium pump activity.

Animals↗
PubMed1978

Circulatory responses of perinatal goats to prostaglandin precursors.

The effects of precursors in the prostaglandin synthetic pathway as well as those of analogs of cyclic endoperoxide intermediates upon the pulmonary and systemic circulations of fetal and newborn goats were examined. Exogenous arachidonic acid increased pulmonary vascular resistance and decreased systemic arterial pressure of fetuses and newborns. The effects of dihomo-gamma-linolenic acid on the circulation are qualitatively similar, but quantitatively less, than those of arachidonic acid. The cyclic endoperoxide analogs were strong pressors in both pulmonary and systemic circulations. The responses to the fatty acid precursors, which are totally blocked by indomethacin and meclofenamate, appear to indicate that they give rise to more than one vasoactive product. Furthermore, exogenous arachidonic acid produces effects which appear to be different from those produced by endogenous pulmonary arachidonic acid.

Animals↗
PubMed1978

Effect of indomethacin on pulmonary vascular response to ventilation of fetal goats.

The effect of indomethacin treatment of the pulmonary vasodilation caused by ventilation of the fetal lung with air was evaluated in anesthetized, exteriorized, fetal goats by means of an open-chest, pump-perfused lung preparation. The decrease in pulmonary vascular resistance that occurs when the fetal lung is ventilated with air consists of two components: 1) a rapid decrease in pulmonary vascular resistance during the first 30 s of ventilation; 2) a slower decline, which continues through the first 10-20 min or more of ventilation. Indomethacin has no effect on the first component. The second component is absent following indomethacin pretreatment. The effect of indomethacin treatment is more pronounced in immature fetuses (less than 90% gestation) than in mature fetuses. Prostaglandin synthase activity appears to be important in the pulmonary vasodilation caused by ventilation of the fetal lungs with air.

Animals↗
PubMed1978

Effects of indomethacin on cardiovascular hemodynamics of goats in hemorrhagic shock.

We examined effects of indomethacin, meclofenamate, and prostaglandin E1 on systemic arterial pressure, heart rate, cardiac output, and systemic vascular resistance of anesthetized juvenile goats in severe hemorrhagic shock. Hemorrhagic shock was characterized by low systemic arterial pressure, decreased vascular resistance, and reduction in cardiac output. In acute experiments, indomethacin (3.4 mg/kg) attenuated the systemic hypotension of hemorrhagic shock. The increase in systemic arterial pressure following treatment with indomethacin was the result of increased systemic vascular resistance. Systemic arterial pressure, heart rate, and cardiac output fell during intravenous prostaglandin E1 infusions (3 micrograms/kg/min for 5 min) in both controls and goats in shock. The effects of prostaglandin E1 were more pronounced and prolonged in goats that had undergone the hemorrhagic-shock-producing procedure followed by indomethacin than in control animals treated with indomethacin but not hemorrhaged. Not only was meclofenamate less effective than indomethacin in increasing the systemic arterial pressures of goats in this type of hemorrhagic shock, but also it attenuated the pressor effects of indomethacin. Substances synthesized via prostaglandin fatty acid cyclo-oxygenase may be involved in the systemic hypotension that is characteristic of hemorrhagic shock.

Animals↗
PubMed1977

Effects of increased intracranial pressure on pulmonary vascular resistance of fetal and neonatal goats.

The effects of increased intracranial pressure on the pulmonary circulation were investigated in fetal and neonatal goats. Pulmonary vascular resistance and systemic arterial pressure increased with elevation of intracranial pressure in neonatal animals. Alpha-adrenergic blockade completely eliminated both of these responses. The response of the fetal pulmonary circulation was unlike that seen in the postnatal animal. Although there was a slight elevation of pulmonary vascular resistance initially, the predominant response was a decrease in resistance. The decrease in fetal pulmonary vascular resistance was unaffected by phenoxybenzamine, but reversed by propranolol. After the beta-adrenergic blockade, increased intracranial pressure produced an increase in pulmonary vascular resistance. Similarly, ventilation of fetal lungs resulted in an increase in pulmonary vascular resistance after increased intracranial pressure. These results demonstrate for the first time that pulmonary vascular resistance may be altered in fetal and neonatal animals by increasing intracranial pressure. The elevation of pulmonary vascular resistance after elevated intracranial pressure must be due to an active pulmonary vascular constriction.

Age Factors↗