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Biomedical subjects

W M Gold

Publications and source records attributed to W M Gold.

At least 73 records · Page 4Linked to original sources
PubMed1983

Augmentation of alpha-adrenergic contractions in the trachealis muscle of living dogs.

Discrepancies exist between reported effects of histamine on the alpha-adrenergic responsiveness of the canine trachealis muscle. Therefore, using an in situ preparation described recently (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 49: 84-94, 1980), we tested the effects of histamine and other agents on alpha-adrenergic responses in the trachealis muscle of 34 anesthetized dogs. Under basal conditions, maximum alpha-adrenergic responses were small [3 +/- 1 (SE) g/cm] compared with those induced by a supramaximal parasympathetic stimulus (45 +/- 3 g/cm). After exposure of the muscle to histamine, responsiveness increased markedly to alpha-adrenergic stimuli, which included tracheal arterial injections of norepinephrine and phenylephrine or electrical stimulation of sympathetic nerves. Augmented alpha-adrenergic responsiveness persisted for 20 min after the end of contractions induced by histamine. Serotonin and long-acting, but not short-acting, cholinergic agonists also potentiated alpha-adrenergic responsiveness. We concluded that exposure of the trachealis muscle in living dogs to a variety of constrictor stimuli potently augmented its alpha-adrenergic responsiveness.

Animals↗
PubMed1983

Diagnostic utility of fiberoptic bronchoscopy in patients with Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome.

The records of 35 adult male patients with suspected Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome were reviewed to determine the diagnostic utility of fiberoptic bronchoscopy. Twenty-two of the 24 patients (92%) shown to have Pneumocystis pneumonia were diagnosed by bronchoscopy; 20 patients were diagnosed after 1 bronchoscopy and 2 patients after 2 bronchoscopies. The sensitivity of bronchoscopy specimens for diagnosing Pneumocystis pneumonia was 79% for transbronchial biopsies (19 of 24), 78% for transbronchial biopsy touch preparations (7 of 9), 55% for bronchial washings (11 of 20), and 39% for bronchial brushings (7 of 18). The overall sensitivity of fiberoptic bronchoscopy was 85% (22 positive of 26 total bronchoscopies). Complications, occurring during 6 of the 37 bronchoscopies, were slight hemoptysis (1 patient), fever (2 patients), septic shock (1 patient), and pneumothorax (2 patients). Fiberoptic bronchoscopy is a safe and effective procedure for making the early diagnosis of Pneumocystis carinii pneumonia in adult male patients with the acquired immune deficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1983

IgE-dependent and ionophore-induced generation of leukotrienes by dog mastocytoma cells.

Isolated dog mastocytoma cells sensitized with dog anti-ragweed IgE and challenged with ragweed antigen generate the C-6 peptide leukotriene (LT) constituents of the slow-reacting substance of anaphylaxis (SRS-A), LTC4 and LTD4, and the potent leukocyte chemotactic factor, LTB4, as well as 15-hydroxyeicosatetraenoic acid (15-HETE), 12-HETE, and 5-HETE. Antigen challenge evoked a mean maximum production of LTC4, LTD4, and LTB4, respectively, of 16.3 ng, 4.6 ng, and 6.7 ng per 10(6) mastocytoma cells within 5 min at 37 degrees C, which was maintained for up to 45 min. The maximum production of leukotrienes by mastocytoma cells activated with optimum concentrations of 0.2 to 1 microM calcium ionophore A23187 was 35% to 50% greater than that achieved by antigen challenge, without alterations in the relative quantities of leukotrienes, but was realized only after 30 min at 37 degrees C. The leukotriene products of mastocytoma cells were identified by high-performance liquid chromatography, spectral properties, and immunoreactivity with mono-specific antisera, and exhibited the same concentration-dependence of biologic activity as authentic synthetic standards. The ratio of quantities of C-6 peptide leukotrienes generated was attributable in part to the rate of peptidolytic conversion of LTC4 to LTD4 in the mastocytoma cells, which was 33% per 30 min at 37 degrees C. The rapid maximum response to IgE-dependent stimulation and the unique spectrum of products distinguishes the secretion of leukotrienes by dog mastocytoma cells from that by basophils and some other types of mast cells and suggests diverse contributions of mast cell leukotrienes to immediate and late hypersensitivity reactions.

Animals↗
PubMed1982

Parasympathetic innervation of the cervical trachealis muscle in living dogs.

In 34 anesthetized dogs, we characterized the pathways by which parasympathetic fibers were carried to the cervical trachealis muscle. Nerves were stimulated electrically, and tracheal tension was monitored in segments of the posterior membrane in vivo as described previously (J.K. Brown et al.; J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 49: 84-94, 1980). Stimulation of superior laryngeal nerves contracted 34 of 34 cranial cervical segments and 2 of 4 caudal cervical segments. Recurrent laryngeal nerves contributed to innervation of 34 of 34 cranial, as well as 4 of 4 caudal, segments. Stimulation of pararecurrent nerves contracted 11 of 34 cranial and 4 of 4 caudal segments. Mechanical effects of esophageal contraction, induced by stimulating pararecurrent nerves, did not alter tension in tracheal segments. Tracheal contractions induced by stimulation of all three pathways simultaneously were significantly less than the sum of contractions produced by stimulating each set individually; this was probably due to anastomoses between terminal neurons, overlap in their anatomic distribution, or intercellular nexuses in trachealis muscle. We conclude that parasympathetic innervation of the canine trachea is by three different neuroanatomic pathways.

Animals↗
PubMed1982

Characterization of tracheal mast cell reactions in vivo. Inhibition by a beta-adrenergic agonist.

In 12 anesthetized dogs, we tested the effects of pharmacologic beta-adrenergic stimulation on the severity of tracheal mast cell reactions in vivo (Am Rev Respir Dis 1979; 119:62). In control dogs, tracheal arterial injections of compound 48/80 produced arteriovenous differences in histamine concentrations across the trachea (35 +/- 15 ng/ml), but not the lung; this finding suggested selective degranulation of tracheal mast cells. Tracheal arteriovenous histamine differences correlated (r = 0.70) with tracheal contractions (12 +/- 4 g/cm) induced by compound 48/80 in these animals. In other dogs, injections of isoproterenol (10 micrograms/kg) before compound 48/80 prevented the development of both tracheal arteriovenous differences and contractions. We concluded that pharmacologic beta-adrenergic stimulation inhibited degranulation of tracheal mast cells. The preparation appears suitable for examining the effects of endogenous stimuli on the severity of mast cell reactions in the central airways of anesthetized dogs.

Adrenergic beta-Agonists↗
PubMed1980

Physiological and pharmacological properties of canine trachealis muscle in vivo.

In 23 dogs anesthetized with chloralose and urethan, we developed a preparation that premitted measurement of isometric tension in segments of the tracheal posterior membrane in situ. Length-tension studies showed an optimal length for contraction in each of 5 segments; in all 5 segments, length was optimal when resting tension was 22-35 g/cm. In 8 other segments, stimuli were delivered by systemic intravenous injections, by electrical stimulation of nerves, or by selective injections into the tracheal circulation; the time between delivery of repeated stimuli required for reproducible responses differed for each form of stimulation. Hypoxemia increased tension by 23.1 +/- 5.5 (SE) g/cm in 10 out of 10 other segments; these increases were the results of reflexes, not direct effects. Because the innervation and vascular supply of these segments were largely intact, we concluded that this preparation permits the study of neurohumoral mechanisms which modulate smooth muscle contraction in a prototypic central airway in vivo.

Acetylcholine↗
PubMed1980

In vivo demonstration of nonadrenergic inhibitory innervation of the guinea pig trachea.

To determine if electrical stimulation of autonomic nerves could excite nonadrenergic inhibitory motor pathways in the guinea pig respiratory system in vivo, we studied the effects of electrical stimulation of the cervical vagi and sympathetic nerve trunks on pressure changes (P(p)) within an isolated, fluid-filled cervical tracheal segment which reflected changes in trachealis muscle tone. We preserved the innervation and circulation of the segment as evidenced by a rise in P(p) with vagus nerve stimulation and a fall in P(p) with intravenous isoproterenol. In five atropine-treated animals, stimulation of the cut vagi or sympathetic nerve trunks resulted in a mean fall in P(p) of 7.9 and 8.2 cm H(2)O, respectively. Treatment with propranolol attenuated the response to sympathetic stimulation but not vagal stimulation. To determine if these relaxation responses were mediated by an adrenergic or nonadrenergic mechanism, we studied an additional five animals that had been treated with 6-hydroxydopamine to destroy adrenergic nerve endings. In 6-hydroxydopamine, atropine, and propranolol-treated animals, sympathetic nerve stimulation decreased P(p) only 0.65 cm H(2)O, confirming the elimination of adrenergic nerve influences, whereas vagus nerve stimulation decreased P(p) 17.7 cm H(2)O. After sectioning the recurrent laryngeal nerves, the mean decrease in P(p) during vagus nerve stimulation was only 3.2 cm H(2)O. These findings demonstrate the presence of nonadrenergic inhibitory nerves in the guinea pig trachea in vivo. They further show that nonadrenergic inhibitory nerve effects are elicited during electrical stimulation of the vagus nerves and that interruption of the recurrent laryngeal nerves diminishes the magnitude of these effects.

Adrenergic Fibers↗
PubMed1979

Experimental canine anaphylaxis: cyclic nucleotides, histamine, and lung function.

We studied the effects of Ascaris suum antigen (iv) in 32 natively allergic, anesthetized dogs. After thoracotomy, bilateral cervical vagotomy, and propranolol, samples of peripheral lung frozen in situ were obtained for measurement of cyclic nucleotides and histamine. Following Ascaris, lung histamine decreased 20.4 +/- 3.7% (mean +/- SE), cAMP increased 391 +/- 122%, and cGMP increased 110 +/- 20% with increased plasma histamine and physiological changes of anaphylaxis. No significant changes occurred in 10 control dogs. Release of histamine, reflecting immunological degranulation of mast cells, correlated closely with the physiological effects of anaphylaxis. beta-Adrenergic stimulation with isoproterenol prevented these physiological effects of anaphylaxis in three dogs studied. Furthermore, the level of cAMP induced in lung tissue by beta-adrenergic stimulation in these dogs correlated with the degree of inhibition of immunologically induced histamine release. These results illustrate the suitability of this experimental preparation to study the biochemical and physiological mechanisms of anaphylaxis in vivo.

Anaphylaxis↗
PubMed1979

A chronic isolated tracheal segment to study airway reflexes in conscious dogs.

Airway reflexes are difficult to study in conscious animals because associated changes in ventilation alter intrathoracic airway dimensions. By studying an isolated segment of extrathoracic trachea, we have overcome this problem. In each of 2 dogs, we created surgically an isolated tracheal segment just below the larynx, sealed at one end and tapered at the other to a 3-mm opening via a skin fistula. A chronic tracheostomy was also created near the thoracic outlet. We monitored intraluminal pressure (Pseg) of the isolated segment to reflect changes in smooth muscle tone. During anesthesia, with pentobarbital, gentle mechanical stimulation of the carina, deflation of the lungs, and asphyxia for one min increased Pseg (+9 to +/- 16 cm H2O). Lung inflation and alveolar hyperventilation decreased Pseg (-9 to -16 cm H2O). Five breaths of 2 per cent histamine aerosol increased Pseg (+5 cm H2O) when resting tone was normal. We also coated lumen of the isolated segment with tantalum powder and documented roentgenologically changes in the size of the segment that reflected changes in smooth muscle tone; constriction and dilation in response to asphyxia and lung inflation, respectively, were demonstrated directly by this technique. In conscious dogs, lung inflation decreased Pseg, and carinal stimulation increased Pseg. Instillation of lidocaine hydrochloride (Xylocaine) into the isolated tracheal segment blocked cough caused by mechanical stimulation of the segment, but carinal stimulation still caused constriction of the segment under these conditions which indicated that afferent, but not effrent parasympathetic innervation of the segment had been blocked selectively. Conversely, instillation of atropine sulfate into the isolated tracheal segment blocked constriction of the segment caused by carinal stimulation, but mechanical stimulation of the segment still caused cough under these conditions, which indicated that efferent, but not afferent parasympathetic innervation of the segment had been blocked selectively. We conclude that an innervated extrathoracic tracheal segment constricts and dilates via cholinergic pathways and is suitable for the study of airway reflexes in conscious dogs.

Animals↗
PubMed1978

Distribution oand pharmacological release of histamine in canine lung in vivo.

We have examined the physiological effects of stored mediators released from airways by compound 48/80 aerosols in anesthetized dogs. In 13 dogs, both mast cell numbers and tissue histamine were related inversely to bronchial internal diameter (P less than 0.0001). Compound 48/80 aerosols degranulated mast cells and decreased histamine content (-29.0 +/- 10.0%; mean +/- SE) in 5-10 mm bronchi, but not in 3-4 mm bronchi or lung parenchyma. This was associated with increased plasma histamine (31.8 +/- 18.4 ng/ml), increased airflow resistance (Rrs: + 452 +/- 257%), decreased lung compliance (-28 +/- 10%), and decreased arterial blood pressure (-41 +/- 6.5%) at 2 min. The increased Rrs was reversed by beta-adrenergic agonists, indicating it was caused by bronchial smooth muscle contraction; prevented by chlorpheniramine, indicating it was caused by histamine action on H1-receptors; and augmented and prolonged by propranolol, suggesting that histamine triggered sympathetic mechanisms which modulated the effect of 48/80. This experimental approach permits the study of mechanisms in vivo which may be involved in the sequence of reactions initiated by antigen-IgE interaction. However, the latter involve not only stored mediators, but also unstored mediators, neural reflexes, and complex cellular interactions.

Aerosols↗
PubMed1977

Rapid, shallow breathing after Ascaris suum antigen inhalation: role of vagus nerves.

In five treadmill-exercising, unsedated dogs, we studied the effect of inhaled Ascaris suum antigen aerosols on minute volume of ventilation (VE), respiratory frequency (f), tidal volume (VT), total pulmonary resistance (RL), and dynamic pulmonary compliance (CLdyn), before and during cooling of the vagus nerves. With the vagi warm, inhaled antigen increased VE (mean + 62%; P less than 0.01)by increasing f (mean + 180%; P less than 0.01), despite a decrease in VT (mean - 42%; P less than 0.01). RL increased (mean + 170%; P less than 0.001) and CLdyn decreased (mean - 43%; P less than 0.005). With the vagi cool, inhaled antigen no longer affected VE, f, or VT (P greater than 0.5), although RL still increased and CLdyn still decreased. Inhalation of a bronchodilator, terbutaline, prevented the broncho-constriction induced by antigen but did not prevent the ventilatory response. We conclude that vagal afferent pathways mediate the ventilatory response to inhaled antigen and suggest that the primary stimulus for this response is not airway narrowing.

Animals↗
PubMed1977

Changes in airway mast cells and histamine caused by antigen aerosol in allergic dogs.

We studied the effect of inhaled specific antigen on airflow resistance, histamine concentration, and mast cell numbers in airway tissues in allergic dogs. In each of six allergic dogs with open chests, inhalation of specific antigen aerosol (Ascaris suum) increased airflow resistance from 0.30+/-0.40 (mean+/-SE) to 2.8+/-0.41 cmH2O/1 per s (P less than 0.05); decreased mast cell number from 38.6+/-3.2 to 24.3+/-4.5 mast cells/mm2 (P less than 0.05); decreased histamine (per mg airway tissue) from 5.3+/-0.4 to 3.5+/-0.2 ng (P less than 0.05) in lobar bronchi 5-7 mm in diam; and released histamine into the blood perfusing the lung, control arterial plasma histamine; 2.8+/-0.64 ng/ml; antigen: 154+/-1.7 ng/ml (P less than 0.005). Specific antigen caused no significant changes in mast cells or histamine in bronchi 1-2 mm in diam. Control aerosols of nonspecific antigen or methacholine did not change levels of mast cells or histamine in airway tissues. These results suggest that experimental canine asthma involves local airway reactions with degranulation of mast cells and histamine release, as well as vagally mediated reflex bronchoconstriction.

Aerosols↗
PubMed1977

Asthma.

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Asthma↗
PubMed1976

Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection.

Inhalation of histamine diphosphate aerosol (1.6 per cent, 10 breaths) produced a 218 +/- 54.6 per cent (mean +/- SE) increase in airway resistance in 16 normal subjects with colds compared with a 30.5 +/- 5.5 per cent increase in 11 healthy control subjects (P less than 0.01). There was no significant difference in mean baseline airway resistance between the two groups. Inhalation of saline produced no significant change in airway resistance in either group. Isoproterenol hydrochloride (0.5 per cent, 1 breath) or atropine sulfate aerosol (0.2 per cent, 20 breaths) each reversed and prevented the increase in airway resistance by histamine, indicating that the bronchoconstriction was caused by smooth muscle contraction and that post-ganglionic, cholinergic pathways were involved in the mechanism. In 6 subjects with colds, citric acid aerosol (10 per cent, 5 breaths) caused bronchoconstriction that lasted up to 30 sec after inhalation, a significantly greater effect than that observed in control subjects or in the same subjects after recovery (P less than 0.05). Prior inhalation of atropine aerosol (0.2 per cent, 20 breaths) prevented the bronchoconstriction after citric acid aerosol in all 6 subjects. The threshold concentration of citric acid that produced cough in 7 subjects with colds was significantly lower than that in control subjects or in the 7 subjects after recovery (P less than 0.05), suggesting that the exaggerated cholinergic response was due to a decreased threshold for stimulation of the rapidly adapting sensory receptors in the airways. We have provided evidence that respiratory viral infections that produce airway epithelial damage temporarily cause these subjects to develop more bronchoconstriction after inhaling smaller doses of histamine than do healthy subjects. The fact that atropine prevents this response and that the threshold to cough is temporarily decreased is compatible with our hypothesis that airway epithelial damage by infection exposes and, thus, "sensitizes" the rapidly adapting airway receptors to inhaled irritants, causing increased bronchoconstriction via a vagal reflex. Damage to the airway epithelium may occur as a result of mechanical factors, inhaled chemicals, and pollutants, such as ozone, infections, or perhaps as a result of the action of materials released endogenously (e.g., from mast cells, white blood cells, or platelets). "Sensitization" of rapidly adapting sensory receptors in the airways may be an important factor in asthma and in other diseases of airways.

Aerosols↗
PubMed1976

Effects of intravenous histamine on static lung compliance and airway resistance in normal man.

Static lung compliance and airway resistance were measured in 30 experiments on 6 healthy subjects after intravenous injection of a bolus of histamine (4 mug per kg of body weight). Analysis of the pooled results showed a significant decrease in static lung compliance (maximal mean decrease,--16 per cent occurring 20 sec after injection). There was no significant change in functional residual capacity or vital capacity after injection of the histamine. Administration of propranolol (a beta-adrenergic blocking agent) did not significantly enhance the responses to histamine. The results suggested that humans, like other species, can constrict peripheral airways sufficiently to produce alterations in the static elastic properties of the lungs.

Adult↗
PubMed1976

The mechanism of rapid, shallow breathing after inhaling histamine aerosol in exercising dogs.

In 4 unsedated, exercising dogs, we studied the effects of inhaled histamine aerosol on minute volume of ventilation, respiratory frequency, tidal volume, total pulmonary resistance, and dynamic pulmonary compliance. Inhalation (5 breaths) of 1 to 2 per cent histamine aerosols increased minute ventilation (mean, 50 per cent; p less than 0.001) by increasing respiratory frequency (mean, 166 percent; P less than 0.001), despite decreasing tidal volume (mean, 42 percent; P less than 0.0001). Total pulmonary resistance increased (mean, 200 per cent; P less than 0.001.) Breathing supplemental O2 did not affect the ventilatory response to histamine. Adding external resistive loads to a dog's airway did not simulate the pattern of rapid, shallow breathing produced by histamine. Inhalation of terbutaline prevented the changes in total pulmonary resistance and dynamic pulmonary compliance but did not alter the ventilatory response to histamine. When conduction in the cervical vagus nerves (which were implanted chronically in skin loops) was blocked by cooling, the ventilatory response to histamine was abolished. We concluded that histamine stimulates breathing by stimulation of receptors whose afferent pathways are in the vagus nerves; the effective stimulus is not bronchoconstriction but is presumably due to direct stimulation of airway receptors.

Aerosols↗