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Biomedical subjects

W M Abraham

Publications and source records attributed to W M Abraham.

At least 145 records · Page 8Linked to original sources
PubMed1983

Duration of mucociliary dysfunction following antigen challenge.

Antigen-induced bronchospasm is associated with an impairment of airway mucociliary clearance, but the duration of this defect has not been examined. In the present study, we determined the time course of mucociliary dysfunction following inhalation challenge with Ascaris suum extract in conscious sheep with hypersensitivity to this antigen. Tracheal mucous velocity (TMV) as an index of mucociliary function, pulmonary resistance (RL), and arterial oxygen tension (Pao2) were measured prior to, immediately after, and serially for 8 h after inhalation challenge. TMV and Pao2 were then measured periodically for at least 2 wk. Immediately after A. suum challenge, mean RL increased to 264% of base line (P less than 0.05), and mean Pao2 decreased to 61% of base line (P less than 0.05). By 2 h postchallenge, mean RL and Pao2 had returned to base line but mean TMV had fallen to 61% of base line (P less than 0.05). Mean TMV reached a minimum of 35% of base line after 5 h (P less than 0.05) and remained significantly depressed between 37% and 54% of base line for 7 days; by day 9, mean TMV had returned to base line. Inhalation challenge with a control antigen (ragweed) failed to alter mean TMV, RL, and Pao2 during the first 8 h and TMV and Pao2 at any time throughout the 2-wk observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Modification of allergic bronchoconstriction by a calcium antagonist: mode of action.

Because both degranulation of mast cells and contraction of airway smooth muscle are dependent upon the influx of calcium, a calcium blocking agent might modify allergic bronchoconstriction by at least these two mechanisms. We treated sheep allergic to Ascaris suum antigen with the calcium antagonist Verapamil prior to airway challenge with an aerosol of Ascaris suum antigen and also investigated the response without pretreatment. Aerosolized Ascaris suum antigen increased mean pulmonary resistance (RL) to 530% of baseline (n = 6). Pretreatment with intravenously administered Verapamil (150 micrograms/kg) increased mean RL to 225% of baseline but bronchoconstriction produced by subsequent antigen challenge was completely prevented. Verapamil did not modify bronchoconstriction produced by aerosols of histamine and carbachol, agents that act upon airway smooth muscle. Further, it did not reverse the increase in RL induced by an intravenous infusion of carbachol. These results suggest that verapamil, at the dosage used, did not prevent allergic bronchoconstriction by a direct action on smooth muscle and therefore was effective by inhibiting the release of mast cell mediators.

Airway Resistance↗
PubMed1983

Characterization of a late phase pulmonary response after antigen challenge in allergic sheep.

We determined if allergic sheep undergo a dual bronchoconstriction in response to inhalation of antigen and whether these responses could be modified by cromolyn or glucocorticosteroids. In 8 conscious sheep with Ascaris suum hypersensitivity, mean pulmonary flow resistance (RL), dynamic lung compliance (Cdyn), thoracic gas volume (Vtg), and arterial oxygen tension (PaO2) were determined prior to, immediately after, and from 2 through 8 h after and 24 h after inhalation challenge with Ascaris suum antigen. Immediately after antigen challenge, mean specific lung resistance (SRL = RL X Vtg) increased by 750% (p less than 0.01) and mean Cdyn and PaO2 decreased by 55% (p less than 0.01) and 37% (p less than 0.01), respectively. By 5 h after challenge, mean SRL and PaO2 had returned to baseline values, whereas mean Cdyn was still below baseline (-19%, p less than 0.05). At 6.5 h, mean SRL increased again to 245% (p less than 0.01) of baseline and remained significantly elevated through the eighth hour. The average increase in mean SRL for the 6.5- to 8-h postchallenge period was 196%, with concomitant decreases in mean Cdyn and PaO2 of 29% and 10%, respectively. By 24 h, all values had returned to baseline. Control inhalation challenge with ragweed, an antigen to which sheep are not sensitive, did not significantly alter SRL, Cdyn, or PaO2 at any time during the 8-h observation period, indicating that the late response was antigen specific and not caused by circadian rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1982

Role of ciliary motility in acute allergic mucociliary dysfunction.

The purpose of this investigation was to determine if abnormal ciliary function contributes to allergic mucociliary dysfunction. In conscious sheep with Ascaris suum hypersensitivity, ciliated cells were obtained with a cytology brush and tracheal mucous velocity (TMV) was determined before and serially for 2 h following antigen inhalation. The recovered cells (also containing mast cells) were suspended in a chamber, and ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of ciliary beat frequency (CBF). One hour after A. suum challenge mean CBF (+/- SE) showed a slight increase from a base-line value of 630 +/- 16 to 716 +/- 30 beats/min (P less than 0.05) when mean TMV was decreased to 57% of base line (P less than 0.05). After 2 h, both mean CBF and TMV returned toward base line. Since possible in vivo actions of chemical mediators liberated by antigen challenge may have been lost after suspension of the brushed cells, we also assessed the effects of antigen on CBF in vitro. A. suum caused a dose-dependent increase in CBF that was blocked by cromolyn sodium. We conclude that 1) allergic mucociliary dysfunction is not caused by a decrease in CBF and 2) antigen-induced release of chemical mediators increases CBF.

Acute Disease↗
PubMed1982

Influence of exercise intensity and duration on biochemical adaptations in skeletal muscle.

The influence of intensity and daily duration of exercise on cytochrome c concentration in the three muscle fiber types was assessed in rats that were treadmill trained for 8 wk (5 days/wk) by 1 of 19 protocols. The importance of exercise duration was determined at six running intensities (10, 20, 30, 40, 50, and 60 m/min). Daily run times resulted in a maximal adaptive change for each running intensity. The general pattern of cytochrome c change, caused by increasing daily run times, followed a first-order manner in all fiber types. The final time-independent asymptotic values were dependent on the intensity of running. In addition, as running intensity was increased, the length of daily run time required to achieve the peak adaptive response was shortened. The intensity influence was very different between fiber types. In the fast-twitch red fiber, the maximal time-independent response at each work intensity was altered by exercise intensity at only submaximal work loads (i.e., the adaptation from 19 to 29 nmol/g was not further increased at 50 and 60 m/min). In contrast, the adaptive response in the fast-twitch white fiber began at 30 m/min (approx 80% VO2max) and increased exponentially as intensity was increased (200% increase at 60 m/min). Whether this different adaptive response between fiber types is due solely to the ordered recruitment of motor units remains to be determined.

Animals↗
PubMed1981

Impaired tracheal mucus transport in allergic bronchoconstriction: effect of terbutaline pretreatment.

The transport velocity of mucus within the trachea, pulmonary resistance, and arterial blood gas composition were measured in intubated conscious sheep with Ascaris suum sensitivity before and during allergic bronchoconstriction. Inhalation of A. suum extract for 15 min increased mean pulmonary resistance significantly from 1.9 cm H2O . L-1 sec-1 to 5.1 cm H2O . L-1 sec-1 after 60 min and to 4.5 cm H2O . L-1 sec-1 after 120 min, while it decreased mean arterial PO2 from 85 to 59 and 53 mm Hg, respectively, without altering arterial PCO2 or pH. This was associated with a decrease in mean mucus velocity from 11.2 to 6.0 and 5.7 mm min-1, respectively. The decrease in mucus velocity was accompanied by endoscopically visible increases in the quantity of tracheal mucus. No alterations in mucus velocity or pulmonary resistance were observed in animals who inhaled a control antigen (ragweed) or breathed a mixture of 10% oxygen 90% nitrogen, which produced a mean arterial PO2 of 51 mm Hg. The administration of 0.25 mg terbutaline sulfate by subcutaneous injection prior to A. suum challenge prevented the changes in mucus velocity, pulmonary resistance, and arterial PO2. We conclude that the decreased mucus velocity in the trachea during antigen-induced bronchoconstriction in conscious sheep is related to the allergic response, and can be prevented by the subcutaneous administration of terbutaline sulfate, a beta adrenergic agonists. This suggests that the protective effect of terbutaline sulfate in antigen-induced bronchoconstriction includes the effect on the associated impairment of mucociliary function.

Animals↗
PubMed1981

Differences in airway reactivity in normal and allergic sheep after exposure to sulfur dioxide.

The effect of breathing 5 ppm sulfur dioxide (SO2) on airway reactivity was studied in both normal and allergic conscious sheep. Allergic sheep were defined as animals in which inhalation of Ascaris suum extract resulted in bronchospasm as evidenced by an increase in mean pulmonary flow resistance (RL), hyperinflation, and a fall in dynamic compliance. Airway reactivity was assessed by measuring the increase of RL after 18 breaths of 0.25% carbachol (c), from an initial RL value obtained after 18 breaths of buffered saline (s) [RL(c-s)]. RL and RL(c-s) were determined prior to, immediately after, and 24 h after exposure to 5 ppm SO4 for 4 h. In both groups RL remained unchanged after SO2 exposure. Prior to exposure, RL(c-s) was not significantly different in seven normal (0.3 +/- 0.1) and seven allergic sheep [0.4 +/- 0.2 (SD) cmH2O X l-1 X s], and there was no significant change in RL (c-s) immediately after SO2 exposure in either group. Twenty-four h later, RL(c-s) RL(c-s) increased to 0.7 +/- 0.8 (P less than 0.2) in normal and to 1.8 +/- 0.9 cmH2O X l-1 X s (P less than 0.01) in allergic sheep. Because the increase in RL(c-s) after 24 h was greater (P less than 0.01) in allergic than in normal sheep, we conclude that SO2 exposure increased airway reactivity more in the former than in the latter.

Animals↗
PubMed1981

Noninvasive ventilatory monitoring by respiratory inductive plethysmography in conscious sheep.

The respiratory inductive plethysmograph is a noninvasive device that has been used to measure tidal volume (VT) in humans from changes in self-inductance of wire coils excited by an oscillator circuit placed about the rib cage and abdomen. We investigated its accuracy in conscious sheep utilizing a new calibration procedure during quiet breathing and breathing associated with bronchospasm provoked by aerosolized carbachol. Seven sheep were intubated with a nasotracheal tube and an esophageal balloon placed for determination of transpulmonary pressure. Base-line mean pulmonary flow resistance (RL) in the sheep was 1.5 +/- 0.7 (SD) cmH2O X l-1 X s. After carbachol inhalation, mean RL increased to a maximum of 8.8 +/- 2.8 cmH2O X l-1 X s (P less than 0.002). AT base line, mean VT estimated by respiratory inductive plethysmography over a 20-s period fell within +/- 6% of spirometry. After carbachol VT in five of the sheep remained close to the initial validation, but in two, it deviated +/- 11% from spirometry. Analysis of the continuous recording of timing and volume components of the breaths revealed that bronchoprovocation did not significantly alter mean VT or frequency. However, there was a slight increase in both parameters resulting in an increase in minute ventilation from 7.6 +/- 2.4 to 9.6 +/- 2.8 l/min (P less than 0.02). Similarly, a slight decline in inspiratory time coupled with the slight rise in VT produced an increase in mean respiratory flow from a base-line value of 0.35 +/- 0.12 to 0.44 +/- 0.17 l/s (P less than 0.05). These results indicate that the respiratory inductive plethysmography accurately monitors breathing pattern in conscious sheep even during severe bronchospasm.

Animals↗
PubMed1981

Effect of pharmacologic agents on antigen-induced decreases in specific lung conductance in sheep.

The purpose of this investigation was to determine the primary mediators responsible for the decrease in specific lung conductance (SGL) after airway challenge with Ascaris suum antigen in allergic sheep. On different occasions, separated by 10 to 14 days, pulmonary resistance and thoracic gas volume were measured in 5 sheep with Ascaris suum hypersensitivity before and for 2 h after a standard inhalation challenge with this antigen. Initially and at the end of the study, inhalation challenge decreased mean SGL to 38 and 44% of baseline, respectively. Pretreatment by intravenous injection of the H1 receptor antagonist chlorpheniramine (2 mg/kg) completely prevented the antigen-induced decrease in SGL. Similar results were obtained with inhalation of the mediator release blocking agent, disodium cromoglycate (1 mg/kg), prior to antigen challenge. The decrease in SGL after inhalation challenge was not modified by pretreatment with the H2 receptor antagonist, metiamide (3 mg/kg), the anticholinergic agent, atropine (0.2 mg/kg), the prostaglandin synthetase inhibitor, indomethacin (2 mg/kg) by intravenous injection, or with inhalation of FPL-55712 (1% solution), an antagonist of slow-reacting substance of anaphylaxis (SRS-A). We concluded that during allergic bronchoconstriction in sheep (1) the decrease in SGL is mediated by histamine via H1 receptors, (2) other liberated or activated mediators including SRS-A do not decrease SGL, and (3) cholinergic reflex mechanisms are not involved in this response.

Airway Resistance↗
PubMed1980

Sulfur dioxide induced airway hyperreactivity in allergic sheep.

The effects of a four-hour exposure (via a Plexiglas hood) to sulfur dioxide (SO2) on airway reactivity was studied in both normal and allergic conscious sheep. Allergic sheep were defined as animals in whom inhalation of Ascaris suum extract resulted in an increase in mean pulmonary flow resistance (RL). Airway reactivity (delta RL) was assessed by measuring the increase in RL after 18 breaths of 0.25% carbachol, from an initial value obtained after 18 breaths of buffered saline. RL and delta RL were determined prior to, immediately after and 24 hours following SO2 exposure in three groups of sheep: six normal sheep exposed to 5 ppm SO2 (group A); six normal sheep exposed to 10 ppm SO2 (group B) and seven allergic sheep exposed to 5 ppm SO2 (group C). RL was not affected by SO2 exposure in any group but both groups B and C showed increases in delta RL 24 hours after exposure. Since the increase in delta RL was greater in group C than in either groups A or B, we conclude that allergic sheep have enhanced susceptibility to the injurious airway effects of SO2.

Airway Resistance↗
PubMed1980

Sensitivity of bronchoprovocation and tracheal mucous velocity in detecting airway responses to O3.

This study was undertaken to determine whether measurements of tracheal mucous velocity or airway reactivity to inhaled carbachol more sensitively detect airway effects of inhaled ozone (O3) in conscious sheep. Dose-response curves of mean pulmonary flow resistance (RL) to carbachol were obtained by measuring RL after five breaths of carbachol aerosol with stepwise increases in drug concentration. The animals then breathed 0.5 ppm O3 through an endotracheal tube for 2 h. The dose-response curves were repeated immediately after the 0.5 ppm O3 exposure and 24 h later. In the eight sheep studied, there were no significant alterations in base-line RL immediately after or 24 h after 0.5 ppm O3. Airway hyperreactivity was not apparent immediately after the sheep breathed 0.5 ppm O3, but it was evident 24 h later. In contrast, six sheep that breathed 0.5 ppm O3 in the same manner for 2 h did not show a significant depression in tracheal mucous velocity the same day or 24 h later. Exposure to 1 ppm O3 for 2 h resulted in airway hyperreactivity immediately after the exposure and elevated base-line RL 24 h later; 2 ppm O3 produced an increase in base-line RL immediately after exposure. We conclude that, in conscious sheep, airway hyperreactivity appears to be a more sensitive indicator of airway effects produced by short-term exposure to 0.5 ppm O3 than depression of tracheal mucous velocity.

Airway Resistance↗
PubMed1979

Determination of pulmonary blood flow by the rebreathing technique in airflow obstruction.

To test the hypothesis that the effect of nonuniform gas distribution on the uptake of inhaled soluble gases in the lung is minimized by rebreathing, we measured pulmonary blood flow by the thermodilution technique, and pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, and alveolar volume by a rebreathing technique in conscious sheep before and immediately after inhalation of a histamine aerosol (4% solution). We also measured pulmonary resistance, distribution of ventilation by multiple-breath N2 washout, and arterial blood gases to monitor airway responses. Histamine inhalation produced a mean pulmonary resistance increase to 621% of baseline accompanied by uneven distribution of ventilation and a decrease in arterial Po2. Despite these alterations in airway function, there were no concomitant changes in pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, alveolar volume, or the ratio of diffusing capacity for CO to alveolar volume. Mean pulmonary capillary blood flow and pulmonary blood flow did not differ from each other before and after histamine inhalation. We conclude that the rebreathing technique for noninvasive measurement of pulmonary hemodynamics is satisfactory in the presence of airflow obstruction.

Airway Obstruction↗
PubMed1977

Factors in delayed muscle soreness.

The possible causes of delayed muscle soreness which occur 24 to 48 hr after exercise were examined from three different approaches, each designed to test an existing hypothesis. Surface electromyograms were used to evaluate the muscle spasm theory; the possibility of actual muscle cell damage was monitored by the presence of myoglobinuria, while the ratio of hydroxyproline/creatinine (OHP/Cr) in 24 hr urine collection was used as a marker for connective tissue involvement. In the first study, although all volunteers developed muscle soreness 24 and 48 hr after exercise, no change in the EMG activity of the sore muscles was observed. Myoglobin excretion was found in 88% of the subjects who developed soreness. However, in a second study, 92% of the subject who performed both moderate and heavy exercise but did not develop muscle soreness had myoglobinuria. In contrast, during a third experiment subjects on gelatin-free diets showed an increase (P less than .1) in the OHP/Cr between control (.020+/-.001) and 48 hr post-exercise (.002+/-.001, X+/-SE). Soreness resulted in all cases. When the OHP/Cr value is taken for the day of maximal soreness, the post-exercise mean increases to .024+/-.001 and the level of significance rises (P less than .005). These observations support the concept that exercise induced soreness may be related to disruption of the connective tissue elements in the muscle and/or their attachments.

Adult↗