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Biomedical subjects

J G Martin

Publications and source records attributed to J G Martin.

At least 19 recordsLinked to original sources
PubMed1992

Effect of negative pressure ventilation in severe chronic obstructive pulmonary disease.

The hypothesis that patients with chronic obstructive pulmonary disease (COPD) have chronic inspiratory muscle fatigue was tested in an effectiveness trial in which negative pressure ventilation (NPV) was used to produce inspiratory muscle rest. In a double-blind study 184 patients with severe COPD were randomly allocated active or sham NPV treatment for a 12-week period of home use. The distance walked in a 6 min walk test was the primary outcome variable. Secondary outcome measures were cycle exercise endurance time, severity of dyspnoea, quality of life, arterial blood gas tensions, and respiratory muscle strength. The percentage reduction in amplitude of the diaphragmatic electromyographic signal multiplied by hours of NPV was used to reflect the dose of NPV so we could examine dose-response relations. Analysis was based on intention to treat. We found no evidence of a clinically or statistically significant difference in any outcome measure between active and sham groups. No dose-response relation was observed. Moreover, the intervention was poorly accepted despite substantial clinical support. We conclude that NPV as used in this study is difficult to apply and ineffective when used with the aim of resting the respiratory muscles in patients with stable COPD.

Aged↗
PubMed1992

Effects of ketotifen on airway responses to allergen challenge in the actively sensitized brown Norway rat.

The purpose of the study was to examine the effect of ketotifen on the airway responses and the recruitment of the inflammatory cells into the airways of sensitized rats after antigen challenge. Twenty-five Brown Norway rats, 7-9 weeks old, were actively sensitized to ovalbumin (OA) (1 mg s.c.) and Bordetella pertussis vaccine (10(9) bacilli i.p.). At 14 days after sensitization rats were anesthetized with urethane (1.1 g/kg i.p.) and intubated endotracheally. Aerosols of OA (5% W/V in saline for 5 min) were administered to control rats (Group A; n = 9), to a low-dose ketotifen group (Group B; 1 mg/kg PO; n = 8) and a high-dose ketotifen group (Group C; 10 mg/kg; PO for 10 days; n = 9). Pulmonary resistance (RL) was measured at baseline, and every 15 min for up to 8 h after OA. The magnitude of the early response was 241 +/- 51% in A (% baseline RL; mean +/- SE), and significantly less in B(119 +/- 7%) and C(131 +/- 16%) (p < 0.01). The late response was significantly lower in C than A but not B. The total cell number in bronchoalveolar lavage at 8 h after OA challenge was significantly higher in A than B and C (p < 0.01). The lymphocyte and eosinophil counts were reduced in B and C compared to A (p < 0.05). A positive correlation was found between the late response and total number of cells recovered in the BAL (r = 0.78) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1992

Effects of prostaglandin E2 on ganglionic transmission in the guinea pig trachea.

We studied the effects of prostaglandin E2 (PGE2) on the contractile responses of in vitro guinea pig tracheal preparations with intact vagal innervation. The preparation was stimulated either through the vagal nerves (NS) or with an electrical field (EFS) and trachealis response was assessed from the pressure change inside the tracheal tube. Ganglionic blockade by hexamethonium inhibited responses to NS but did not affect EFS while both responses to NS and EFS were abolished by atropine or tetrodotoxin. This indicates that responses to both stimulation modalities were mediated by cholinergic nerves but that NS involved a ganglionic relay whereas EFS did not. Within the frequency range of 0.1-20 Hz, there was a gradual increase in the pressure generated by the trachealis muscle with increasing frequency of stimulation. The frequency-response relationship was similar for NS and EFS. Thus, the ganglion does not appear to play an important filtering or amplifying role under those conditions. PGE2 (1-50 mM) produced a concentration-dependent inhibition of NS and EFS without affecting responses to exogenous acetylcholine (ACh). This suggests that the main action of PGE2 is to reduce ACh release from post-ganglionic nerve terminals. PGE2 inhibited EFS to a larger extent than NS; we postulate a possible excitatory effect of PGE2 on neurotransmission in the airway ganglia.

Animals↗
PubMed1992

The relationship between late asthmatic responses and antigen-specific immunoglobulin.

The aim of this study was to examine the relationships between allergen-induced early and late airway responses and antigen-specific IgE, IgG, and lymphocyte subsets in blood and bronchoalveolar lavage (BAL). Brown Norway rats were sensitized at 7 weeks of age with ovalbumin (1 mg s.c.) with use of Bordetella pertussis as an adjuvant. Three weeks after sensitization, animals were anesthetized and challenged with an aerosol of ovalbumin (5% wt/vol in saline) for 5 minutes. Each animal was studied for 8 hours with repeated measurements of lung resistance. Blood was obtained at 0, 1, 2, and 3 weeks before ovalbumin challenge. Ovalbumin-specific IgE and IgG were determined by ELISA. No specific antibody was detectable before sensitization. Ovalbumin-specific IgE and IgG rose between 1 to 2 weeks after sensitization and peaked at 3 weeks. The IgE level did not correlate with the magnitude of either the early or the late responses. In a similar manner no correlation existed between the magnitude of specific IgG and the late response. However, a significant inverse correlation (r = -0.73; p < 0.01) occurred between specific IgG and the early response. No correlation occurred between the ratio of helper (W3/25 +) to suppressor (OX-8 +) lymphocytes in blood and BAL and airway responses to allergen. The size of the early and late responses were correlated, suggesting a common stimulus. Despite the blunting of the early response by repeated sensitization the late response was unaffected, suggesting that the factors that determine the physiologic expression of the early and late responses are different.

Animals↗
PubMed1992

Induction of sleep apnoea with negative pressure ventilation in patients with chronic obstructive lung disease.

BACKGROUND: Negative pressure ventilation provides intermittent non-invasive ventilatory assistance for patients with advanced chronic obstructive lung disease. Upper airway obstruction during sleep, a reported complication of the technique, may, however, limit its clinical applicability. METHODS: The effects of nocturnal negative pressure ventilation on ventilation and on indices of sleep quality were investigated in five patients with severe chronic obstructive lung disease (mean (SE) FEV1 31% (3%) predicted) who had completed three months of nightly negative pressure ventilation. Subjects underwent overnight polysomnography on consecutive nights, the first night serving as a control and negative pressure ventilation being provided on the second night. Ventilators were adjusted to result in maximum suppression of the peak phasic electromyogram signal from the diaphragm. RESULTS: Negative pressure ventilation resulted in substantial increases in episodes of obstructive apnoea and hypopnoea (mean (SE)/h 59.3 (19.8) v 3.2 (1.3) on control nights). Most obstructive events, however, were associated with under 3% oxygen desaturation, and the lowest recorded values for overnight oxygen saturation were similar on the two study nights. Negative pressure ventilation was also associated with significant increases in the frequencies of movement arousals and changes in sleep stage. CONCLUSIONS: Negative pressure ventilation applied during sleep to patients with advanced chronic obstructive lung disease may result in the development of recurrent episodes of apnoea and hypopnoea as well as altered sleep quality, which could limit its clinical applicability.

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PubMed1992

In vivo airway reactivity: predictive value of morphological estimates of airway smooth muscle.

Airway responsiveness to methacholine and other bronchoconstrictors is highly variable within and among species. The aim of the experiments in this report was to evaluate the importance of the quantity of airway smooth muscle as a determinant of intra- and inter-species variability in airway responsiveness. To do this we established concentration-response curves to methacholine in a sample of normal guinea pigs as well as in rat, rabbit, and dog. After challenge we excised the lungs for the quantitation of smooth muscle by morphometry. Animals were anesthetized with pentobarbital and mechanically ventilated using a Harvard ventilator. Aerosols of methacholine were administered in progressively doubling concentrations from 0.0625 to 256 mg/mL for a period of 30 s for each concentration. The maximal response, determined from pulmonary resistance (RL), and the concentration of methacholine required to effect 50% of the maximal RL were determined. After provocation testing the lungs were removed and fixed with 10% Formalin. Midsagittal sections and parahilar sections were stained with hematoxylin-phloxine-saffron for microscopic examination of smooth muscle. The images of all airways in the sections were traced using a camera lucida side-arm attachment and digitized using commercial software. The area of the airway wall occupied by smooth muscle was determined and standardized for airway size by dividing it by the square of the epithelial basement membrane length. The variability in airway smooth muscle in the intraparenchymal airways was significantly greater between than within individual guinea pigs (n = 13). This was not true of extraparenchymal airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Low-frequency pulmonary impedance in rabbits and its response to inhaled methacholine.

We assessed pulmonary mechanics in six open-chest rabbits (3 young and 3 adult) by the forced oscillation technique between 0.16 and 10.64 Hz. Under control conditions, pulmonary resistance (RL) decreased markedly between 0.16 and 4 Hz, after which it became reasonably constant. Measurements of alveolar pressure from two alveolar capsules in each rabbit showed that the large decrease of RL with increasing frequency below 4 Hz was due to lung tissue rheology and that tissue resistance was close to zero above 4 Hz. Estimates of resistance and elastance, also obtained by fitting tidal ventilation data at 1 Hz to the equation of the linear single-compartment model, gave values for RL motion that were slightly higher than those obtained by forced oscillations at the same frequency, presumably because of the flow dependence of airways resistance. After treatment with increasing doses of aerosolized methacholine, RL and pulmonary elastance between 0.16 and 1.34 Hz progressively increased, as did the point at which the pulmonary reactance crossed zero (the resonant frequency). The alveolar pressure measurements showed the lung to become increasingly inhomogeneously ventilated in all six animals, whereas in the three younger rabbits lobar atelectasis developed at high methacholine concentrations and the alveolar capsules ceased to communicate with the central airways. We conclude that the low-frequency pulmonary impedance of rabbits exhibits the same qualitative features observed in other species and that it is a sensitive indicator of the changes in pulmonary mechanics occurring during bronchoconstriction.

Administration, Inhalation↗
PubMed1992

A peptidergic component to vagally induced tracheal vasodilation in the dog.

The purpose of the study was to determine the extent that peptidergic afferent and efferent pathways contribute to vagally induced vasodilation in the trachea of the dog. The change in vascular resistance of the tracheal branch of the cranial thyroid artery and the trachealis responses were determined in 28 anesthetized, paralyzed, and mechanically ventilated dogs. After propranolol (2 mg/kg) and phentolamine (1.5 mg/kg), stimulation of the superior laryngeal nerves (NS; 15 Hz, 7 V, 2 ms, 30 s) caused a decrease in vascular resistance of 11.7 +/- 0.8% and a tracheal contraction of 5.2 +/- 4.7 cmH2O. Atropine (1.5 mg/kg) reduced the fall in vascular resistance to 4.7 +/- 0.8% (P less than 0.01), whereas tracheal contraction was abolished. Thiorphan (1.5 mg), a neutral endopeptidase inhibitor, augmented the decrease in vascular resistance (8.8 +/- 0.6%; P less than 0.01) to NS. After hexamethonium (0.5 mg/kg), NS still caused a small decrease in TVR (2.9 +/- 0.9%; P less than 0.05), which was abolished by capsaicin. In atropinized dogs, capsaicin reduced the fall in vascular resistance after NS; the residual vasodilation was virtually abolished by hexamethonium. Acetylcholine (10(-3) mg/kg) decreased vascular resistance (15.7 +/- 3.0%), and the effect was abolished by atropine. We conclude that there is noncholinergic nonadrenergic vagally induced tracheal vasodilation that is peptidergic. The peptidergic vasodilation appears to be mediated by both afferent and efferent pathways.

Acetylcholine↗
PubMed1992

Comparison of upper and lower airway responses of two sensitized rat strains to inhaled antigen.

The purpose of the study was to investigate the relationships between upper airways responses and pulmonary responses of two strains of highly inbred rats to inhaled antigen. To do this we measured the upper and lower airways resistance for 60 min after challenge of Brown-Norway rats (BN; n = 13) and an inbred rat strain (MF; n = 11), derived from Sprague-Dawley, with aerosolized ovalbumin (OA). Rats were actively sensitized with OA (1 mg sc) using Bordetella pertussis as an adjuvant. Two weeks later the animals were anesthetized and challenged. Tracheal pressure, esophageal pressure, and airflow were measured, from which total pulmonary resistance was partitioned into upper airway and lower pulmonary resistance (RL). The peak upper airway response to inhaled OA was similar in BN (1.89 +/- 0.66 cmH2O.ml-1.s; n = 7) and MF (2.85 +/- 0.68 cmH2O.ml-1.s; n = 6). The lower airway response to OA challenge was substantially greater in BN, and RL changed from 0.07 +/- 0.01 to 0.34 +/- 0.13 (n = 6; P < 0.05). The MF did not have any significant increase in RL after challenge; the baseline RL was 0.12 +/- 0.02 and only reached a peak value of 0.15 +/- 0.05 (n = 5; P = NS). Lower airway responsiveness of BN (n = 10) to serotonin, an important mediator early allergic airway responses, was similar to MF (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Effect of body posture on concentration-response curves to inhaled methacholine.

Lung volume has been shown to be a major determinant of the bronchoconstrictor response to inhaled methacholine (MCh). Because a change in body posture from sitting to supine is associated with a reduction in lung volume, we hypothesized that airway responsiveness to inhaled MCh should be affected by body posture. Responsiveness to MCh was assessed in both sitting and supine postures on separate days in 10 subjects aged 24 to 42 yr. Subjects inhaled aerosols of saline and MCh in progressively doubling concentration (0.125 to 256 mg/ml). Responses were assessed by measuring partial and complete forced expiratory flow-volume curves (PEFV and MEFV, respectively). As indices of airway responsiveness, we took the MCh concentration ([MCh]) at which the FEV1 fell by 10% relative to postsaline (PC10), the maximal percentage fall in FEV1 (MR), the [MCh] at which FEV1 reached 50% of MR (EC50), and the [MCh] at which the flow at 20% vital capacity on PEFV curves fell by 20% relative to postsaline (FP20). Responsiveness to MCh was increased in the supine compared with the sitting posture. In the sitting posture, the geometric mean values of MR, PC10, and FP20 were 16.3%, 16.3 mg/ml, and 2.0 mg/ml; supine they were 29.9% (p less than 0.009), 3.0 mg/ml (p less than 0.02), and 0.6 mg/ml (NS), respectively. EC50 did not change with posture. These results are consistent with the notion that airway responsiveness is influenced by airway-parenchymal interdependence and indicate that the results of bronchial provocation testing in the supine posture cannot be directly compared with those in the upright posture.

Adult↗
PubMed1992

Effect of interleukin-2 on the airway response to antigen in the rat.

To evaluate the hypothesis that lymphocyte stimulation can modify the bronchoconstrictive response to inhalational challenge with an allergen, we administered interleukin-2 (IL-2), an important lymphokine in lymphocyte activation and proliferation, to actively sensitized rats. Brown Norway rats received either human recombinant IL-2 (n = 8) or its vehicle (n = 7) twice a day from the ninth to the fourteenth day after active sensitization to ovalbumin (OA) and were challenged with an aerosol of OA. Lung resistance (RL) during the early response increased to a maximum of 698 +/- 230% and 180 +/- 26% of baseline values in the animals receiving IL-2 and vehicle, respectively (p less than 0.025). The late response was threefold greater in IL-2-treated than in vehicle-treated animals (p = 0.01). IL-2 increased OA-specific IgG levels in the serum, but it did not significantly affect total or specific IgE levels. IL-2 caused an inflammatory infiltrate around the airways with significant increases in eosinophils, lymphocytes, and mast cells prior to antigen challenge. Our results indicate that stimulation of cell-mediated immunity can affect airway responsiveness to antigen.

Animals↗
PubMed1992

Morphometric changes during the early airway response to allergen challenge in the rat.

The purpose of this study was to determine the relative contributions of airway wall edema and smooth muscle contraction to the early response (ER) of allergic bronchoconstriction. Brown Norway rats, 6 to 7 wk old, were sensitized with ovalbumin (OA). Anesthetized rats were challenged with either OA or saline 2 wk later. Pulmonary resistance (RL) was measured every minute until either it increased to 150% of the baseline, defined as a significant ER, or until 15 min elapsed. Eight OA-challenged test rats with a significant ER and eight saline-challenged control rats were used for morphometric studies. The lungs were quick-frozen with liquid nitrogen, processed with freeze substitution, and sagittal sections (5 microns) were stained with hematoxylin and eosin. The airway lumen subtended by the epithelial basement membrane (LuB) and cross sectional airway wall area (AW) of all airways were measured by camera lucida and digitization. The LuB and AW of each airway was standardized for size by dividing by the ideal airway lumen (LuBideal), which was calculated from the length of basement membrane, assuming a perfect circle in the unconstricted state. The cumulative frequency distribution of the LuB/LuBideal for the airways from test rats was shifted to the left compared with the control rats (p less than 0.01), indicating airway narrowing after challenge. Airway narrowing increased as a function of airway size. Cumulative frequency distributions of AW/LuBideal showed that there was a significant increase in the wall thickness of only the small airways of test animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1992

Identification of adenylate cyclase-coupled histamine H2 receptors in guinea pig tracheal smooth muscle cells in culture and the effect of dexamethasone.

Histamine acts on airway contractile elements through at least two different receptor subtypes: H1, which mediates Ca(2+)-dependent contraction, and H2, which stimulates cyclic adenosine monophosphate (cAMP) synthesis and possibly relaxation. The aim of this study was to determine the relative contribution of the different receptor subtypes to histamine-stimulated cAMP production by guinea pig tracheal smooth muscle (GPTSM) cells in primary culture. Histamine and N-alpha-methylhistamine induced concentration-dependent cAMP synthesis; these effects were entirely blocked by 10(-4) M cimetidine, an H2-receptor antagonist, whereas 10(-6) M thioperamide, a selective H3 blocker, was ineffective. The H3 agonist, R-(alpha)-methylhistamine, did not stimulate cAMP synthesis. Triprolidine, an H1 antagonist, did not modify histamine (10(-5) M)-stimulated cAMP synthesis. Histamine (10(-5) M) doubled [Ca2+]i in GPTSM. A 24-h pretreatment of GPTSM cells with 10(-6) M dexamethasone enhanced cAMP synthesized in response to 10(-5) M histamine and to 5 x 10(-6) M forskolin but did not significantly alter either the affinity or the binding capacity for [3H]-tiotidine, an H2-receptor antagonist. These results indicate that GPTSM cells in culture express H2 but not H3 receptors, which are linked to adenylate cyclase; their functional expression does not seem to be modulated by the concurrent activation of H1 receptors, whose presence in GPTSM is evidenced by a histamine-stimulated increase in [Ca2+]i. The most likely site of action of dexamethasone in enhancing histamine-stimulated cAMP synthesis is at the level of adenylate cyclase since the steroid had no effect on the H2 receptor itself.

Adenylyl Cyclases↗
PubMed1992

Feeding studies in rats with mineral hydrocarbon food grade white oils.

This investigation compared the effects of feeding rats diets containing food grade white oil processed by either conventional oleum treatment or the more modern method of catalytic hydrogenation. In two separate experiments, male or female Fischer-344 rats were given free access for 90 days to diets containing 0, 10, 100, 500, 5,000, 10,000, or 20,000 ppm of either oleum-treated white oil (OTWO) or hydrotreated white oil (HTWO). There were no mortalities and no adverse clinical signs associated with feeding either white oil. Treatment-related effects evidenced by hematological, clinical chemical, and pathological changes were generally dose-related and more marked in female than in male rats, and the OTWO caused a greater pathological response than the HTWO. Tissue residues of saturated hydrocarbons were up to 5.2 times higher in female rats than in males. Rats fed 5,000 ppm or more of either white oil showed dose-related alterations in several hematological and clinical chemistry variates associated mainly with hepatic damage or functional alteration. At necropsy, mesenteric lymph nodes were enlarged, and increases in weight of liver, kidney, and spleen were significant. Microscopic changes were characterized by multifocal lipogranulomata in mesenteric lymph node and liver. No changes were observed in rats fed OTWO or HTWO for 90 days at dietary concentrations of 10 or 100 ppm, equivalent to a minimum intake of 0.65 and 6.4 mg/kg/day, respectively. Differences in degree of pathological response associated with each oil may have been due to their differences in specification rather than processing method.

Animals↗
PubMed1991

A randomized clinical trial of negative pressure ventilation in severe chronic obstructive pulmonary disease: design and methods.

This report documents the design and methods of a randomized clinical trial designed to test the effectiveness of home negative pressure ventilation in patients with severe chronic obstructive pulmonary disease. Active negative pressure ventilation was compared with a sham version of the treatment after a pre-trial assessment had indicated the feasibility of the latter. Over 1200 patients in the metropolitan Montreal area were screened. Of these, 348 patients were recruited to enter a 4-week stabilization period, and 184 were subsequently randomized to receive either active or sham negative pressure ventilation. A 5-day in-hospital period was used to train patients in ventilator use and obtain baseline measures of exercise capacity, lung function, respiratory symptoms, and quality of life. Home ventilation treatment took place during a following 12-week period. Respirator use was recorded both from patient logs and from concealed meters installed in the units. Patients received four home visits by physiotherapists during the 12-week period and returned for follow-up to the hospital 4 and 12 weeks post-discharge for reassessment.

Aged↗