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Biomedical subjects

E W Spannhake

Publications and source records attributed to E W Spannhake.

At least 55 records · Page 3Linked to original sources
PubMed1985

Effect of repeated antigen exposure on antigen-and mediator-induced bronchospasm in sheep.

We studied the effects of repeated exposures of antigen on airway reactivity to mediators of anaphylaxis and immediate response to the antigen. Seven antigen-sensitive sheep were exposed to aerosols of Ascaris suum antigen 5 times biweekly; a control group of seven sheep underwent the same exposure regimen with saline vehicle. Sheep were assigned to experimental (Ascaris) or control groups so the distribution of animals with regard to bronchial reactivity to mediators was about the same. Airway reactivity was assessed by determining the effects of aerosolized histamine (10-1,000 micrograms), prostaglandin F2 alpha (PGF2 alpha, 10-300 micrograms), and a stable analogue of thromboxane A2 (U-46619, 1-100 micrograms) on lung resistance (RL) and dynamic lung compliance (Cdyn). Before treatment, experimental and control groups showed similar changes in RL and Cdyn, with analogue greater than histamine greater than PGF2 alpha. At the highest dose of each agonist, mean increases in RL were 50, 123, and 29%, respectively, and mean decreases in Cdyn were 21, 45, and 12%. During the first 15-min exposures to antigen aerosol, mean RL had increased by 125% and Cdyn decreased by 38% of base-line values; hyperinflation following the exposures reduced the changes to 56 and 31%, respectively. Changes in RL and Cdyn during the final antigen exposures and following postexposure hyperinflation were reduced significantly (P less than 0.05) compared with the initial exposures. Baseline RL and Cdyn before and after the exposures to antigen or saline were not significantly different. Airway reactivity to histamine, PGF2 alpha, or analogue was not significantly altered in these atropinized animals over the range of doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1985

Increased in vitro airway responsiveness in sheep following repeated exposure to antigen in vivo.

We have studied the effect of repeated in vivo antigen exposure on in vitro airway responsiveness in sensitized sheep. Fourteen sheep underwent five biweekly exposures to aerosolized Ascaris suum antigen or saline. Following this exposure regimen, the animals were killed and tracheal smooth muscle and lung parenchymal strips were prepared for in vitro studies of isometric contraction in response to histamine, methacholine, prostaglandin F2 alpha, and a thromboxane A2 analogue. No alteration in tracheal smooth muscle responsiveness was observed between saline- and antigen-exposed tissue. In contrast, by use of lung parenchymal strips as an index of peripheral airway responsiveness, significant increases in responsiveness to histamine and a thromboxane A2 analogue (10(-6) and 10(-5) M) were observed in antigen-exposed tissue compared with saline controls. These results demonstrate that repeated antigen exposure in vivo selectively increase the responsiveness of peripheral lung smooth muscle to certain chemical mediators of anaphylaxis.

Animals↗
PubMed1985

Influence of mediators of anaphylaxis on collateral ventilation and the lung periphery of the dog.

The relative activities of three bronchoconstrictive mediators of anaphylaxis, prostaglandin (PG) D2, PGF2 alpha and histamine, were investigated in anesthetized dogs using two different measures of peripheral lung reactivity: resistance to flow through collateral airways (Rcoll) and dynamic lung compliance (Cdyn). In the collateral system, the three agonists exhibited approximately 3-fold differences in their relative activities when administered by rapid injection into the superior vena cava, with PGD2 greater than PGF2 alpha greater than histamine. PGD2 was approximately three times more active than PGF2 alpha in reducing Cdyn, whereas responses to PGF2 alpha and histamine were equivalent. These relationships were unchanged in vagotomized animals. Pretreatment with atropine (1 mg/kg) significantly attenuated changes in Rcoll, but had only small and inconsistent effects on changes in Cdyn. Although the time to initial response in both measures of peripheral airways reactivity was similar, the time to maximal response in Rcoll was approximately twice that of Cdyn. In lung parenchymal strips, the rank order of contractile activity of the three mediators was opposite that observed in the peripheral airways in vivo. These data demonstrate that airflow through the collateral system can be modulated by mediators of anaphylaxis in the pulmonary circulation and suggest that such mediators may influence ventilation/perfusion relationships in the lung periphery through their differential effects on peripheral airways and other parenchymal contractile elements. The present study also indicates that the determinants of flow through the collateral system exhibit certain basic pharmacologic and physiologic differences from those of Cdyn and suggests that these two measures of peripheral airways reactivity are not equivalent.

Airway Resistance↗
PubMed1983

In vivo metabolism of dihomo-gamma-linolenic acid to bronchoactive products in the canine lung.

We investigated the effects of dihomo-gamma-linolenic acid (DGLA), the fatty acid precursor to the monoenoic prostaglandins, on pulmonary mechanics in the intact chest, artificially ventilated dog. Under conditions of normal airway tone, intravenously administered DGLA produced a modest, dose-related increase in lung resistance and decrease in dynamic lung compliance. These responses were approximately 30-100 times less than those produced by arachidonic acid. The bronchoconstrictive responses to DGLA were abolished by prior inhibition of the cyclooxygenase with indomethacin. PGD1 was equal in activity to PGF1 alpha in causing constriction of central and peripheral airways of the dog. PGE1 was without significant airway effects in these animals under conditions of resting airway tone. We conclude that DGLA is a moderately good substrate for the cyclooxygenase pathway enzymes of the canine lung, producing products having a predominantly bronchoconstrictive effect. This bronchoconstriction is most likely due to the synthesis of PGD1 and PGF1 alpha and is not due to the synthesis of lipoxygenase pathway products.

8,11,14-Eicosatrienoic Acid↗
PubMed1981

Pulmonary vascular responses to prostaglandins.

Pulmonary vascular responses to the endoperoxide PGH2, an endoperoxide analog, primary prostaglandins (PGE2, PGF2 alpha, and PGD2), arachidonic acid, and PGI2 were compared in the intact chest of the cat and dog. The primary prostaglandins as well as PGH2 and a stable endoperoxide analog all increase lobar arterial pressure in the dog and cat when injected into the lobar artery. Since pulmonary blood flow was held constant with a pump and left atrial pressure was unchanged, the increases in lobar arterial pressure indicate an increase in pulmonary vascular resistance. The endoperoxide analog and PGF2 alpha were very potent pressor agents in the pulmonary vascular bed. The primary prostaglandins and the endoperoxide analog had significant contractile activity in isolated segments of bovine intrapulmonary artery and vein and in canine intrapulmonary vein. The endoperoxide analog. PGF2 alpha, PGD2, and arachidonic acid, in addition to increasing pulmonary vascular resistance, increased bronchomotor tone. In contrast to the effects of the primary prostaglandins and the endoperoxide analog, PGI2 had vasodilator activity in the pulmonary vascular bed and this activity was enhanced when pulmonary vascular tone was elevated. The prostaglandin precursor arachidonic acid produced both increases and decreases in pulmonary vascular resistance, depending on dose and rate of administration, and these responses were blocked by indomethacin. These data indicate that the prostaglandins have marked but diverse activity in the pulmonary vascular bed.

Animals↗
PubMed1981

Metabolism of prostaglandin endoperoxide by microsomes from cat lung.

It has been reported that the prostaglandin (PG) precursor, arachidonic acid, produces divergent hemodynamic responses in the feline pulmonary vascular bed. However, the pattern of arachidonic acid products formed in the lung of this species is unknown. In order to determine the type and activity of terminal enzymes in the lung, prostaglandin biosynthesis by microsomes from cat lung was studied using the prostaglandin endoperoxide, PGH2, as a substrate. The major products of incubations of PGH2 with microsomes were thromboxane (TX) B2 (the major metabolite of TXA2), 6-keto-PGF1 alpha (the breakdown product of PGI2) and 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT). Formation of TXB2 was markedly reduced by imidazole. Tranylcypromine decreased the formation of TXB2 and HHT and inhibited the formation of 6-keto-PGF1 alpha. At low PGH2 concentrations, equal production of TXB2 and 6-keto-PGF1 alpha was observed. However, as PGH2 concentration increased, 6-keto-PGF1 alpha production approached early saturation while TXB2 production increased in a linear fashion. These results suggest that enzymatic formation of TXA2 and PGI2 is a function of substrate availability in the lung. These findings provide a possible explanation for the divergent hemodynamic responses to arachidonic acid infusions at high and low concentrations in the feline pulmonary vascular bed.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

6-keto-PGE1 exhibits more potent bronchodilatory activity in the cat than its precursor, PGI2.

In anesthetized, vagotomized an mechanically ventilated cats, we investigated the bronchodilatory activity of the PGI2 metabolite, 6-keto-PGE1, relative to PGI2 and PGE2. In a range of doses from 0.3-10.0 microgram, i.v. injection of 6-keto-PGE1 produced a dose-related decrease in central airway resistance (RL) in animals bronchoconstricted by 5-HT. This effect on RL was 3-10 times greater than that produced by i.v. PGI2. At the lower doses, 6-keto-PGE1 was also more potent than PGI2 in increasing dynamic lung compliance; their effects upon semi-static compliance were not significantly different. Comparison of the bronchopulmonary effects of the two prostanoids did not show any consistent difference in their temporal patterns. In contrast to PGI2 or PGE2, 6-keto-PGE1 had minimal pulmonary vasomotor activity. Inhibition of the cyclooxygenase pathway with sodium meclofenamate had no effect on the bronchopulmonary actions of 6-keto-PGE1 or on its duration of action. These data indicate that 6-keto-PGE1 is a more potent bronchodilator than PGI2 in the cat. They further suggest that conversion of PGI2 to 6-keto-PGE1, if it occurs to an appreciable extent in the lung in vivo, could enhance bronchodilatory activity.

Alprostadil↗
PubMed1981

Pulmonary vasoconstrictor responses to graded decreases in precapillary blood PO2 in intact-chest cat.

The effects of graded changes in pulmonary lobar arterial blood PO2 and ventilatory hypoxia were investigated in the intact-chest cat under conditions of controlled lobar blood flow. A reduction in precapillary PO2 from systemic arterial levels to below 60 Torr increased lobar arterial pressure. Ventilation with 10% O2 increased lobar arterial pressure, and responses to ventilatory hypoxia and precapillary hypoxemia were independent but additive. The magnitude of the pressor response to precapillary hypoxemia was similar in experiments in which the lung was autoperfused with right atrial blood or cross-perfused with aortic blood from a donor cat breathing 10% O2. During retrograde perfusion of the ventilated lung, a reduction in pulmonary venous PO2 to 40 Torr did not affect inflow pressure. The present data suggest that sensor sites upstream to the alveolar-capillary region in segments of lobar artery unexposed to alveolar gas sense a reduction in precapillary blood PO2 and elicit a pulmonary vasoconstrictor response. The sensor site in the precapillary segment is independent of sensors in the alveolar-capillary-exposed segment region, and the effects of stimulation of both sensors on the pulmonary vascular bed are additive. In addition, the present data indicate that sensors in the pulmonary veins do not sense a reduction in PO2 in venous blood and elicit a vasoconstrictor response. These data suggest that the mixed venous blood PO2 may exert an important regulatory role in controlling pulmonary arterial pressure and pulmonary vascular resistance in the cat under normal and pathological conditions.

Animals↗
PubMed1980

Reversal of 5HT-induced bronchoconstriction by PGI2: distribution of central and peripheral actions.

In anesthetized, mechanically ventilated, and vagotomized cats, we studied the distribution of the bronchodilatory effects of prostaglandin I2 (PGI2) in central and peripheral airways. In the intact-chest cat, bolus intravenous injection of PGI2 in a range of doses from 3 to 100 micrograms produced dose-dependent reversal of 5-hydroxytryptamine- (5HT) induced bronchoconstriction. Bronchodilatory effects were manifested by a pronounced decrease in central airways flow resistance, as estimated by measurement of lung resistance and by an increase in dynamic lung compliance (Cdyn). A similar distribution and magnitude of airway effects were produced by intravenous administration of PGE1 in a range of doses from 0.3 to 10 micrograms. PGI2 significantly reversed the frequency dependence of compliance induced by infusion of 5HT. The PGI2 metabolite, 6-keto-PGF1 alpha, was without effect on pulmonary mechanics. Comparison of right- versus left-heart administration of PGI2 did not point to a significant role of the bronchial circulation in the airway effects of PGI2. Comparison of the effects of PGI2 and PGE1 on cat bronchial and parenchymal strips contracted by 5HT showed both prostaglandins to have predominant action on bronchial smooth muscle with PGI2 being 3-10 times less active than PGE1. These data suggest that PGI2 has central airway bronchodilator activity, similar to, but less potent than PGE1. In addition, they suggest that PGI2 has significant dilator activity in certain peripheral areas of the lung, as well.

Animals↗