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Biomedical subjects

J M Drazen

Publications and source records attributed to J M Drazen.

At least 253 records · Page 14Linked to original sources
PubMed1985

The effects of a fish-oil-enriched diet on pulmonary mechanics during anaphylaxis.

The pulmonary mechanical responses observed after antigen challenge in 2 groups of sensitized, mepyramine-treated, mechanically ventilated guinea pigs were compared: one group was fed a diet rich in fish oil and the other a control diet enriched with beef tallow. The lung tissue of animals fed a fish-oil-enriched diet for 9 to 10 wk incorporated eicosapentaenoic acid (EPA) and docosahexaenoic acid, which constituted 8 to 9% of the total fatty acid content, whereas these alternative fatty acids constituted less than 1% of total fatty acid content of the lung tissue of animals receiving a diet supplemented with beef tallow. With mepyramine pretreatment, animals receiving a fish oil diet exhibited a significantly greater decrease in dynamic compliance from 1.5 through 4.5 min after antigen challenge than did animals receiving a beef fat diet, whereas the decrements in pulmonary conductance were comparable. The combination of indomethacin and mepyramine markedly augmented the antigen-induced decrease in pulmonary mechanics in animals receiving a beef fat diet but not in those receiving a fish oil diet, such that the overall responses of the 2 groups were similar. These findings indicate that the fish oil diet and the indomethacin pretreatment of animals receiving the beef fat diet each facilitates the nonhistamine-mediated bronchoconstrictor response in pulmonary anaphylaxis.

Airway Resistance↗
PubMed1985

Density gradient study of bronchial mucus aspirates from healthy volunteers (smokers and nonsmokers) and from patients with tracheostomy.

Because it is difficult to obtain, little is known of bronchial mucus from the normal human airway; it has been mainly studied as sputum expectorated in chronic bronchitis with particular attention to epithelial glycoprotein. We have now applied density gradient methods to study this and other macromolecules and lipids in normal airway mucus. After lavage at bronchoscopy, mucus was aspirated from six normal volunteers, that include one light and two heavy smokers. This normal mucus has been compared with that obtained from four patients with tracheostomy because of respiratory muscle paralysis due to neurological disease. The normal aspirates contained small threads of mucus, the tracheostomy aspirates viscous blobs of jelly, a difference in physical appearance reflected in macromolecular yields, 0.3-1 mg/ml and 6-24 mg/ml respectively. On analytical ultracentrifugation normal mucus showed no discernible material in the buoyant density region typical of epithelial glycoprotein (1.5 g/ml): Virtually all the material migrated to the miniscus and was predominantly lipids and proteins. A trace amount of material recovered from a higher density region (greater than or equal to 1.6 g/ml) was found to contain both glycoprotein and proteoglycan. Aspirates from the heavy smokers contained appreciable amounts of material with typical buoyant density (approximately 1.5 g/ml) but still with features of proteoglycan. In contrast in tracheostomy aspirates epithelial glycoprotein of typical buoyant density and chemical composition accounted for up to 25% of nondialyzable material. We conclude that under normal conditions typical epithelial glycoprotein is virtually absent from airway mucus and that the glycoconjugate present has features of glycoprotein and proteoglycan.

Adult↗
PubMed1984

Effect of vasoactive intestinal peptide on vagally mediated tracheal pouch relaxation.

Vasoactive intestinal peptide (VIP) was studied as a possible neurotransmitter of nonadrenergic inhibition in guinea pig tracheas in vivo, by examining the effects of VIP and isoproterenol on pressure changes induced by nerve stimulation in an isolated, fluid filled, tracheal segment (tracheal pouch). VIP though less potent than isoproterenol produced a dose-dependent relaxation of the pouch. Incubation of the histamine-constricted tracheal pouch with isoproterenol resulted in pouch relaxation and a significant (P less than 0.005) loss of pouch responsiveness to sympathetic nerve stimulation, while non-adrenergically mediated pouch relaxation resulting from vagal stimulation in the presence of atropine was inhibited to a much smaller degree. VIP incubation produced relaxation of the histamine-constricted pouch and resulted in a greater loss of responsiveness to vagal than to sympathetic stimulation (P less than 0.02). By demonstrating loss of vagal responsiveness after VIP in guinea pigs, sympathectomized by 6-hydroxydopamine combined with incubation of the pouch with propranolol to eliminate circulating beta adrenergic inhibition, the effects of VIP incubation on vagally induced pouch relaxation were confirmed to be non-adrenergic in nature.

Animals↗
PubMed1984

Leukotriene E4-induced airway hyperresponsiveness of guinea pig tracheal smooth muscle to histamine and evidence for three separate sulfidopeptide leukotriene receptors.

Bronchial hyperresponsiveness to contractile agonists and nonspecific irritants is a characteristic feature of bronchial asthma. The mechanisms causing this hyperirritability are unknown. The existence of separate receptors for leukotrienes C4 and D4 (LTC4 and LTD4) has been demonstrated previously by physiologic and radioligand binding studies. The rank order of potency of the sulfidopeptide leukotrienes for contracting tracheal spirals [leukotriene E4 (LTE4) greater than LTD4 = LTC4] is different from that for contracting parenchymal strips (LTD4 greater than LTE4 greater than LTC4), thereby suggesting the existence of a separate receptor for LTE4. We now report that LTE4, the most stable of the leukotrienes comprising slow reacting substance of anaphylaxis, enhances the contractile response of guinea pig tracheal spirals but not of parenchymal strips to histamine in a time- and dose-dependent fashion. The ability of LTE4 to increase histamine responsiveness occurred after removal of the free agonist and recovery of the tissues to baseline tensions and was not produced by leukotrienes C4 and D4, which elicited the same magnitude of contraction of tracheal smooth muscle as LTE4. These findings suggest that LTE4-induced airway hyperirritability is not mediated by the contractile response per se and may be mediated through a receptor distinct from those for leukotrienes C4 and D4.

Airway Resistance↗
PubMed1984

Physiological bases for new approaches to mechanical ventilation.

High frequency ventilatory (HFV) techniques offer potential advantages over conventional forms of mechanical ventilation in patients with diverse forms of respiratory insufficiency. In some respects, HFV challenges conventional physiologic concepts regarding gas transport in the lung. We review hypotheses regarding the mechanism of gas transport and provide a brief perspective on current clinical applications of these techniques.

Humans↗
PubMed1984

Intra-airway gas mixing during high-frequency ventilation.

We examined the intra-airway gas transport mediated by high-frequency oscillations (HFO) in 10 nonintubated healthy volunteers using a method based on comparisons of single-breath N2-washout curves obtained after various durations of breath hold or high-frequency oscillations. With a mathematical analysis based on Fick's law of diffusion we computed the local transport parameter, effective diffusivity, during oscillations of frequency 2-24 Hz and tidal volume 10-120 ml and during breath hold alone. Local effective diffusivity increased with both oscillatory frequency and tidal volume at all levels in the tracheobronchial tree; the enhancing effect of tidal volume on local effective diffusivity was more pronounced than that of frequency so that effective diffusivity was greater with larger tidal volume at fixed frequency-tidal volume product (f . VT). The greatest enhancement of gas mixing within the lung during HFO (over breath hold) was seen in the central airways. In previous studies examining CO2 removal rate during HFO (J. Clin. Invest. 68: 1475, 1981), we found that CO2 output was also greater with larger tidal volume at fixed f . VT, and we attributed this to an end constraint imposed by a fresh gas bias flow. Results of the current study, performed without a bias flow, indicate that bias flow end constraint does not solely account for the observed dependence of CO2 output on frequency and tidal volume.

Adult↗
PubMed1984

Gas mixing during high-frequency ventilation: an improved model.

A model for gas transport during high-frequency ventilation incorporating recently derived empirical forms for the effective diffusivity in oscillatory gas flow through a symmetrical branching network is proposed. The model accounts for the movement of gas among airways with changing cross-sectional area by using a moving-reference-frame analysis. The analysis technique incorporates the convective purging of the bias flow at the airway opening. The model predicts that although the cycle-averaged CO2 elimination rate (VCO2) depends most strongly on the product of frequency and tidal volume (VT), VT has an effect on its own, a finding consistent with published observations. This "VT effect" is due primarily to the oscillatory movement of gas from more central regions into peripheral regions where large cross-sectional areas promote efficient CO2 transport by molecular diffusion. Although the VT effect exists independent of the presence of a bias flow, placing the bias flow near the main carina can enhance the VT effect substantially. As VT is increased to values in the range of ordinary tidal breaths, VCO2 predicted by the model achieves close agreement with VCO2 deduced from conventional gas exchange theory.

Biological Transport↗
PubMed1984

Ozone-induced airway hyperreactivity in the guinea pig.

The predominant airway site and mechanism underlying ozone (O3)-induced respiratory hyperresponsiveness was examined in anesthetized guinea pigs and in vitro tissue preparations. Animals exposed to 1.0 or 1.2 ppm O3 (1 h) demonstrated an enhanced airway response to subcutaneous histamine compared with air-exposed animals. The anatomic site of hyperresponsiveness most likely did not involve the parenchyma, since quasi-static deflationary pulmonary compliance was decreased to a similar extent by histamine in air- and O3-preexposed animals. In contrast, the conducting airways were probably involved as changes in pulmonary resistance elicited by subcutaneous histamine were greater in O3- than in air-exposed animals. Neither atropine nor vagotomy abolished this enhanced responsiveness induced by O3. Although vagal interruption did not alter responsiveness, O3-exposed animals demonstrated greater respiratory responses to efferent electrical stimulation of the vagi than air-exposed animals. This suggests the site of hyperresponsiveness may be located distal to the site of efferent stimulation, possibly in the smooth muscle itself or in its microenvironment.

Acid-Base Equilibrium↗
PubMed1984

High-frequency ventilation.

Complete physiological understanding of HFV requires knowledge of four general classes of information: 1) the distribution of airflow within the lung over a wide range of frequencies and VT (sect. IVA), 2) an understanding of the basic mechanisms whereby the local airflows lead to gas transport (sect. IVB), 3) a computational or theoretical model in which transport mechanisms are cast in such a form that they can be used to predict overall gas transport rates (sect. IVC), and 4) an experimental data base (sect. VI) that can be compared to model predictions. When compared with available experimental data, it becomes clear that none of the proposed models adequately describes all the experimental findings. Although the model of Kamm et al. is the only one capable of simulating the transition from small to large VT (as compared to dead-space volume), it fails to predict the gas transport observed experimentally with VT less than equipment dead space. The Fredberg model is not capable of predicting the observed tendency for VT to be a more important determinant of gas exchange than is frequency. The remaining models predict a greater influence of VT than frequency on gas transport (consistent with experimental observations) but in their current form cannot simulate the additional gas exchange associated with VT in excess of the dead-space volume nor the decreased efficacy of HFV above certain critical frequencies observed in both animals and humans. Thus all of these models are probably inadequate in detail. One important aspect of these various models is that some are based on transport experiments done in appropriately scaled physical models, whereas others are entirely theoretical. The experimental models are probably most useful in the prediction of pulmonary gas transport rates, whereas the physical models are of greater value in identifying the specific transport mechanism(s) responsible for gas exchange. However, both classes require a knowledge of the factors governing the distribution of airflow under the circumstances of study as well as requiring detail about lung anatomy and airway physical properties. Only when such factors are fully understood and incorporated into a general description of gas exchange by HFV will it be possible to predict or explain all experimental or clinical findings.

Animals↗
PubMed1984

Influence of the endotracheal tube on CO2 transport during high-frequency ventilation.

Low-volume, high-frequency ventilation (HFV) delivered via an endotracheal tube can maintain eucapnia in both humans and animals. Because recent animal studies have suggested that a substantial fraction of the resistance to gas transport during HFV can be attributed to the presence of the endotracheal tube, we evaluated the importance of the endotracheal tube on carbon dioxide elimination (VCO2) during HFV in humans. We compared the effectiveness of delivering the fresh gas bias flow at the proximal and the distal end of an endotracheal tube. For each bias flow position, we ventilated patients using tidal volumes of 60 ml or less and frequencies from 0.5 to 12 Hz. In each case, VCO2 was approximately 50% greater when the fresh gas was introduced at the carinal end of the endotracheal tube. Thus, the endotracheal tube contributed about one third of the resistance to HFV-induced CO2 transport in these patients. These results indicate that the position of the fresh gas source strongly influences the effectiveness of HFV.

Adult↗
PubMed1984

Morphologic correlation of physiologic changes caused by SO2-induced bronchitis in dogs. The role of inflammation.

Chronic bronchitis was induced in 6 mongrel dogs by exposure to SO2 gas for 6 to 18 months. All of the dogs developed cough and mucus hypersecretion. Chronic airway obstruction and decreased airway responsiveness to inhaled histamine developed in 5 of the dogs. Histologic changes in dogs evaluated after SO2 exposure included significant mucous gland hypertrophy and hyperplasia, epithelial thickening, and a decrease in the number of luminal cells containing undischarged secretory granules. Acute and chronic inflammation were found in the dogs with airway obstruction and decreased responsiveness to histamine, but such inflammation was absent in the one dog that failed to develop physiologic changes. After a period of recovery from SO2 exposure of 9 to 21 months, inflammation regressed dramatically and the other histologic changes returned toward normal. Physiologic changes regressed somewhat in those dogs that had had changes. These findings suggest that inflammation may be an important factor influencing the development of airway obstruction and altered airway responsiveness in the setting of chronic bronchitis.

Airway Resistance↗
PubMed1984

Physiological basis and interpretation of indices of pulmonary mechanics.

Tests of pulmonary mechanical function provide information about the state of the lungs, both airways and parenchyma. This information can be extracted from measurements made in experimental animals, especially the combined determination of pulmonary resistance and dynamic compliance. This report discusses the rationale upon which effects of an intervention on the lung periphery can be distinguished from those on more central airways. Further, practical considerations involved in making these measurements are discussed.

Carbon Dioxide↗
PubMed1984

Immunologically induced generation of tetraene and pentaene leukotrienes in the peritoneal cavities of menhaden-fed rats.

The generation of sulfidopeptide leukotrienes and leukotriene B (LTB) in response to an IgG-mediated immune complex reaction in the peritoneal cavities of rats fed either a menhaden oil-supplemented diet or a beef tallow-supplemented diet for 9 to 10 wk was determined with the combined techniques of radioimmunoassay (RIA) and reverse-phase high performance liquid chromatography. Rats on the fish fat diet (FFD) incorporated eicosapentaenoic acid (EPA) into pulmonary and splenic tissues with an EPA:arachidonic acid ratio of approximately 2:1, whereas rats on the beef fat diet (BFD) showed no detectable EPA. The estimated total quantities of immunoreactive sulfidopeptide leukotrienes generated by each group of rats were similar, ranging from 70 to 99 ng/ rat in the FFD groups and 65 to 109 ng/rat in the BFD groups; for rats on the FFD this total included the pentaene products LTC5, LTD5, and LTE5 in quantities ranging from 24 to 39 ng/rat. The total quantities of immunoreactive LTB generated in the two groups of rats were similar, being 6 to 29 ng LTB4/rat for the BFD groups and the sum of LTB4 and LTB5 of 8 to 36 ng/rat for the FFD groups. There was a two- to seven-fold preferential generation of immunoreactive LTB5 over LTB4 in the FFD rats. LTC5 was equipotent with LTC4 in contracting guinea pig pulmonary parenchymal strips and ileal tissues. In contrast, LTB5 was 1/30 to 1/60 as potent and did not reach the same maximum as LTB4 in eliciting neutrophil chemotaxis. The finding that FFD favors the immunologic generation of LTB5, which has attenuated biologic activity when compared to LTB4, suggests that EPA-enriched tissues may produce less pro-inflammatory activity than tissues that are EPA-poor.

Animals↗
PubMed1984

High-frequency ventilation.

Recent experiments have demonstrated that normal pulmonary gas exchange rates can be achieved in humans and test animals using high frequency (1 to 30 Hz), low volume (comparable to, or less than the dead space volume) oscillations imposed at the mouth or through an endotracheal tube. This review examines the different methods of High Frequency Ventilation (HFV) and the mechanisms thought to be responsible for gas transport, which are intrinsically different than in normal tidal breathing. Several potentially important transport mechanisms are discussed, including augmented dispersion, bidirectional streaming due to asymmetric velocity profiles, direct ventilation of near alveoli, and intercompartmental mixing or pendelluft. Models used to predict the rate of gas exchange in HFV are described in terms of their theoretical and experimental bases. The model predictions are compared to results of physiologic experiments.

Animals↗
PubMed1984

Lung inflation during high-frequency ventilation.

We investigated the relationship between mean airway pressure and lung volume during low-tidal-volume, high-frequency ventilation (HFV). Eight patients requiring mechanical ventilatory support for treatment of respiratory insufficiency were studied by imposing rapid (60 to 600 breaths/min) oscillations with low tidal volumes (50 to 150 ml) at a constant mean airway pressure of 5 cm H2O. Despite this constant mean airway pressure, lung volume increased substantially during the oscillation period in 7 of 8 subjects, as indicated both by an increase in thoracoabdominal dimensions and by an increase in respiratory system relaxation pressures after the oscillations were stopped. For each patient in whom these changes occurred, the degree of lung inflation rose progressively with increases in either frequency or tidal volume. Given this dissociation between lung volume and mean airway pressure, some index of lung volume or alveolar pressure should be monitored to minimize the likelihood of adverse effects during HFV.

Adult↗
PubMed1983

Airway constriction in normal humans produced by inhalation of leukotriene D. Potency, time course, and effect of aspirin therapy.

Five normal human subjects inhaled aerosols generated from solutions of leukotriene D (LTD) to determine the bronchoconstrictor potency and the time course of airway obstruction produced by this constituent of slow-reacting substance of anaphylaxis. The dose-effect and time-effect curves were compared with curves similarly generated for the well-characterized airway constrictor histamine. Leukotriene D was, on average, 5,900 times more potent than histamine on a molar basis in producing an identical decrement in maximal expiratory flow rate at 30% of control vital capacity above residual volume. In addition, although LTD had a rapid onset of effect, similar to that of histamine, the airway obstruction produced by LTD was longer lasting, thereby reflecting more closely the response of asthmatic allergic individuals to antigen inhalation. The response of these subjects to inhalation of LTD was not altered by ingestion of aspirin, suggesting that the airway obstruction was not mediated by cyclooxygenase products of arachidonic acid.

Adult↗