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J G Martin

Publications and source records attributed to J G Martin.

At least 163 records · Page 9Linked to original sources

Interrupter resistance elucidated by alveolar pressure measurement in open-chest normal dogs.

The interrupter method for measuring respiratory system resistance involves rapidly interrupting flow at the mouth while measuring the pressure just distal to the point of interruption. The pressure signal observed invariably exhibits two distinct phases. The first phase is a very rapid jump, designated delta Pinit, which occurs immediately on interruption of flow. The second phase is designated delta Pdif and is a further pressure change in the same direction as delta Pinit but evolving over several seconds. The physiological interpretations of delta Pinit and delta Pdif have been somewhat unclear. Delta Pinit has been taken to equal the pressure drop across the pulmonary airways, possibly with a contribution from the tissues of the respiratory system. Delta Pdif can arise, in principle, from two sources: gas redistribution throughout the lung after interruption of flow and stress recovery within the tissues. To resolve these issues we performed interruption experiments on anesthetized paralyzed, tracheotomized, open-chest normal dogs during passive expiration while measuring alveolar pressures at three sites with alveolar capsules. We found that, in the absence of the chest wall, delta Pinit reflects only the resistance of the airways and that delta Pdif can be ascribed almost entirely to the stress recovery properties of lung tissues.

Airway Resistance↗

Antigen challenge of sensitized rats increases airway responsiveness to methacholine.

We measured airway responsiveness to methacholine (MCh) of highly inbred rats before and after six inhalational challenges with antigen. Ten Brown-Norway rats (130-216 g) that were actively sensitized to ovalbumin (OA) received six challenges with OA at 5-day intervals beginning 19 days after sensitization. An aerosol of OA (5% wt/vol) was inhaled for 1, 2, 5, and 10 min or until pulmonary resistance (RL) increased by at least 50%. Challenges with aerosolized MCh were performed immediately before and 14 days after sensitization, 2 days after the 3rd OA exposure, and 2, 7, 12, and 17 days after the 6th OA challenge. Four unsensitized rats underwent inhalational challenges with MCh over an equivalent time period. Responsiveness to MCh was calculated as the concentration of MCh required to increase RL to 200% of the control value (EC200RL). Seven out of 10 rats in the experimental group reacted to the first OA challenge with an immediate increase in RL of greater than 50% of control (range 70-550%). Three animals were unreactive to OA. Base-line EC200RL for all rats undergoing sensitization was 2.13 mg/ml (geometric mean), and it did not change significantly after sensitization (2.05 mg/ml). However, EC200RL of the rats that reacted to OA (n = 7) decreased significantly after 3 (1.11 mg/ml; P less than 0.005) and 6 OA exposures (0.96 mg/ml; P less than 0.005). The increase in responsiveness to inhaled MCh was present 17 days after the last OA exposure (EC200RL = 1.40 mg/ml; P less than 0.05). EC200RL of neither the unreactive sensitized rats (n = 3) nor the control rats (n = 4) changed after OA challenges.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Relationship between in vivo airway reactivity and in vitro responsiveness of tracheal smooth muscle in inbred rats.

We evaluated the in vivo and in vitro airway responses to cholinergic stimulation in two highly inbred strains of rats. Five Fisher and six Lewis rats inhaled aerosols of doubling concentrations of methacholine (MCh). Pulmonary resistance (RL) was measured before and after each MCh inhalation. The concentration of MCh required to double RL (EC200RL MCh) was calculated. Spirally cut tracheal strips were suspended in an organ bath and the isometric tension was recorded. Cumulative concentration-response curves to carbachol were obtained using concentrations ranging from 10(-9) to 10(-3) M in half-log increments. The maximum tension (Tmax) developed and the negative log of the molar concentration required to induce 50% of Tmax (pD2) were calculated. The geometric mean of ED200RL MCh for the Fisher group was significantly lower than that for the Lewis group (0.68 and 2.66 mg/ml, respectively; p less than 0.05). No significant difference was found for Tmax (0.67 +/- 0.11 vs. 0.50 +/- 0.11 g) and pD2 value (6.24 +/- 0.08 vs. 6.21 +/- 0.22 -log M), indicating a similar contraction of tracheal smooth muscle. We therefore conclude that (1) in vivo airway responsiveness is strain-related and genetically determined in the rat; (2) that there is no correlation between in vivo and in vitro airway response to cholinergic stimulation and (3) that intrinsic properties of airway smooth muscle do not account for the differences observed in airway responsiveness in vivo.

Airway Resistance↗

Late airway responses to antigen challenge in sensitized inbred rats.

We studied the magnitude and the time course of changes in pulmonary resistance (RL) after aerosol challenge with chicken ovalbumin (OA) of 15 sensitized, highly inbred Brown-Norway (BN) rats. Animals were actively sensitized and 2 wk later were challenged through the airways. Airway responses of sensitized animals were compared to those of 6 control animals challenged with sufficient methacholine (MCh) to at least double RL and to 4 unsensitized control rats challenged with OA. Ten of 15 rats in the experimental group displayed an early response (ER), defined as an increase in RL of at least 50% within 1 h of challenge. A late response (LR) was considered to have occurred when the value of RL exceeded the mean plus 2 standard deviations of all the measurements taken from 1 h after challenge to the end of the experiment. Two rats died less than 240 min after OA challenge with RL greater than 200% baseline. The remaining 13 were studied for a total duration that ranged from 390 to 720 min and of these animals 10 demonstrated LRs. Maximal RL during the LR after OA was 287 +/- 49% (SE) baseline (range, 129 to 760) versus 115 +/- 15% (75 to 176) for control animals after MCh (p less than 0.01) and 52 +/- 3% (51 to 142; p less than 0.01) for unsensitized control animals after OA. There was no correlation between the magnitude of ER and LR; 3 LRs occurred in the absence of detectable ERs. The median time to the peak of the LR was 450 min; median duration of LRs was 90 min (range, 30 to 135 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Apamin and nonadrenergic inhibition of guinea pig trachealis.

Apamin has been shown to antagonize the nonadrenergic, noncholinergic (NANC) inhibitory system in guinea pig taenia coli. We have examined the effects of apamin on the nonadrenergic noncholinergic inhibitory system and its putative transmitters in isolated guinea pig trachea. Electrical field stimulation (ES) of isolated trachea pretreated with atropine and propranolol evoked reproducible relaxations that were blocked by tetrodoxin, but were unaffected by apamin. Vasoactive intestinal peptide (VIP), adenosine (AD), and adenosine triphosphate (ATP) produced concentration-dependent inhibition of histamine (H)-induced contractions of isolated trachea but the inhibitory actions of these agents were not significantly affected by apamin. In contrast, apamin virtually abolished ES-evoked relaxations in guinea pig isolated taenia caeci, and reduced the inhibition of H-induced contraction by ATP from 40% to 1%. We conclude that neither the NANC inhibitory system in the guinea pig trachea nor its putative mediators VIP, AD, and ATP are antagonized by apamin, in contrast to taenia caeci.

Adenosine↗

The effect of a proximal compliance on interrupter measurements of resistance.

The interrupter method for measuring respiratory system resistance involves rapidly interrupting flow at the airway opening while measuring the pressure just distal to the site of interruption. In general, the pressure signal obtained exhibits an initial rapid change (delta Pinit) accompanied by rapid damped oscillations, followed by a further slow change to a steady-state plateau level. Delta Pinit is thought to principally reflect the resistance of the pulmonary airways Raw. We have developed a computer model capable of simulating the main features observed in an interrupter pressure signal. We show that the distinct phases in the pressure signal can be obscured by the existence of a compliant compartment between the airways and the occluding valve (e.g. the cheeks and pharynx) when Raw is increased. Our results suggest that supporting the cheeks may enable one to estimate Raw with the interrupter technique in the presence of mild to moderate bronchoconstriction, but that with severe bronchoconstriction (Raw increased 10-fold above normal) it may not be possible.

Adult↗

The effect of ephedrine upon uterine artery blood flow velocity in the pregnant guinea pig subjected to terbutaline infusion and acute hemorrhage.

The purpose of the present study was to determine the effect of intravenously administered ephedrine upon uterine artery blood flow velocity (UBFV) in the gravid guinea pig subjected to terbutaline infusion and acute hemorrhage. Ephedrine, 1.0 mg/kg, was administered intravenously to ten chronically instrumented pregnant guinea pigs near term, before and after intravenous infusion of terbutaline and acute hemorrhage. Before terbutaline and hemorrhage, ephedrine increased maternal mean arterial pressure (MMAP) by 30 +/- 1% (P = .0001) and 17 +/- 1% (P = .0001) at 30 s and at 1 min after injection, respectively; UBFV was decreased by 10 +/- 4% (P less than .01) and 14 +/- 4% (P less than .01) at 1 min and at 90 s after injection, respectively. Infusion of terbutaline (1.5-6.0 ug X kg-1 X min-1) increased maternal heart rate (MHR) by 22 +/- 1% (P = .0001), decreased MMAP by 13 +/- 2% (P = .0001), and decreased UBFV by 24 +/- 3% (P = .0001). During hypotension resulting from acute hemorrhage, ephedrine, 1.0 mg/kg, was superior to placebo in restoring MMAP and UBFV toward the prebleed values. The authors concluded that ephedrine, 1.0 mg/kg, results in a small, transient decrease in UBFV in the normotensive gravid guinea pig. However, ephedrine aids restoration of UBFV in the gravid guinea pig rendered hypotensive by acute hemorrhage during terbutaline infusion.

Animals↗

Partitioning of airway responses to inhaled methacholine in the rat.

We measured the changes in upper and lower airway resistance after inhalation of aerosols of methacholine (MCh) in doubling concentrations (16, 32, 64, and 128 mg/ml) in 11 anesthetized nonintubated spontaneously breathing rats. Upper airway resistance (Ru) increased from a control value of 0.48 +/- 0.04 cmH2O X ml-1 X s (mean +/- SE) to 0.85 +/- 0.15 after 128 mg/ml MCh, whereas lower airway resistance (Rlo) increased from 0.11 +/- 0.03 to 0.21 +/- 0.04. However, there was no correlation between the magnitudes of the changes in Ru and Rlo. In a further seven anesthetized spontaneously breathing rats aerosols of MCh were delivered into the lower airways via a tracheostomy and resulted in increases in Rlo from a control value of 0.20 +/- 0.03 to 0.66 +/- 0.12 after 128 mg/ml MCh. Ru also increased to approximately double its control value. We conclude that inhaled MCh causes narrowing of both Ru and Rlo in the anesthetized rat, the changes in Ru and Rlo are not correlated, and changes in Ru can occur when MCh deposition occurs only in the lower airways.

Aerosols↗

Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans.

We examined the effects of lung volume on the bronchoconstriction induced by inhaled aerosolized methacholine (MCh) in seven normal subjects. We constructed dose-response curves to MCh, using measurements of inspiratory pulmonary resistance (RL) during tidal breathing at functional residual capacity (FRC) and after a change in end-expiratory lung volume (EEV) to either FRC -0.5 liter (n = 5) or FRC +0.5 liter (n = 2). Aerosols of MCh were generated using a nebulizer with an output of 0.12 ml/min and administered for 2 min in progressively doubling concentrations from 1 to 256 mg/ml. After MCh, RL rose from a base-line value of 2.1 +/- 0.3 cmH2O. 1-1 X s (mean +/- SE; n = 7) to a maximum of 13.9 +/- 1.8. In five of the seven subjects a plateau response to MCh was obtained at FRC. There was no correlation between the concentration of MCh required to double RL and the maximum value of RL. The dose-response relationship to MCh was markedly altered by changing lung volume. The bronchoconstrictor response was enhanced at FRC - 0.5 liter; RL reached a maximum of 39.0 +/- 4.0 cmH2O X 1-1 X s. Conversely, at FRC + 0.5 liter the maximum value of RL was reduced in both subjects from 8.2 and 16.6 to 6.0 and 7.7 cmH2O X 1-1 X s, respectively. We conclude that lung volume is a major determinant of the bronchoconstrictor response to MCh in normal subjects. We suggest that changes in lung volume act to alter the forces of interdependence between airways and parenchyma that oppose airway smooth muscle contraction.

Adult↗

Effect of endogenous prostaglandins on acetylcholine release from dog trachealis muscle.

We used a radioenzymatic technique to measure effects of the prostaglandin synthesis inhibitor indomethacin and of exogenous prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) on acetylcholine (ACh) efflux from canine tracheal smooth muscle (TSM) during sustained electrical field stimulation (EFS; 2 Hz, 2 ms pulse duration, 50 V for 15 min). ACh efflux from indomethacin (INDO, 10(-6) M)-pretreated and control TSM increased with consecutive stimulations. However, efflux of ACh was greater in INDO-treated than control muscles. INDO increased the tension produced by TSM in response to EFS. Neither PGE2 (10(-8) M) nor PGI2 (10(-6) M) had any effect on ACh efflux from INDO-pretreated TSM during the first of three periods of EFS. However, PGI2 and PGE2 prevented the progressive increase in ACh efflux observed on subsequent stimulations. PGE2 but not PGI2 decreased contractions of TSM caused by EFS. Our results demonstrate that endogenous prostaglandins, probably PGE2, do inhibit EFS-evoked ACh release from canine TSM in vitro, but suggest that these prostaglandins modulate EFS-evoked contractions predominantly by postsynaptic mechanisms.

Acetylcholine↗

Changes in upper and lower airway resistance after inhalation of antigen in sensitized rats.

To assess the contribution of upper and lower airways to the changes in pulmonary resistance after inhalation of antigen by sensitized rats, we measured changes in upper airway resistance (Ru) and lower pulmonary resistance (Rlo) after inhalation of ovalbumin (OA) in anesthetized, spontaneously breathing, sensitized BN rats. Aerosols of antigen were inhaled through the nose and through a tracheostomy in random order; there was a 1-h recovery interval between challenges. After inhalation of OA through the nose, Ru increased from 0.441 +/- 0.057 (mean +/- 1 SE) to 1.342 +/- 0.504 cm H2O X ml-1 X s (n = 6; p less than 0.05) and Rlo increased from 0.099 +/- 0.017 to 0.269 +/- 0.08 cm H2O X ml-1 X s (p less than 0.05). Changes in Ru and Rlo were strongly correlated (r = 0.938; p less than 0.001). After OA was inhaled through the tracheostomy, Rlo increased from 0.089 +/- 0.021 to 0.152 +/- 0.041 cm H2O X ml-1 X s (p less than 0.05). However, Ru did not change significantly. Pretreatment of the lower airways with inhaled atropine did not affect the magnitude of the changes in Ru after inhalation of OA through the nose but significantly attenuated the response of the lower airways. We conclude that when sensitized, spontaneously breathing rats inhale antigen through the nose, the predominant reaction occurs in the upper airways; changes in upper airway resistance do not result from reflexes originating in the lower airways; lower airway responses are mediated in part by cholinergic mechanisms.

Administration, Inhalation↗

Airway responses to aerosolized methacholine in the cat. Effects of partial or complete vagosympathectomy.

To explore the role of airway innervation as a determinant of airway responsiveness to inhaled cholinergic agonists, we studied the effects of partial or complete section of the cervical vagosympathetic trunk on the magnitude of methacholine-induced bronchoconstriction in the chloralose-urethane-anesthetized, mechanically ventilated cat. An initial concentration-response curve to methacholine was constructed to identify the concentration required to cause a twofold to threefold rise in mean pulmonary resistance (RL). Using this concentration, 3 consecutive challenges (C1, C2, and C3) were then performed at 30-min intervals in 4 groups of cats. After a control challenge (C1), the parasympathetic (n = 9), sympathetic (n = 6), or both branches (n = 4) of the cervical vagosympathetic trunks were sectioned. Sham cats (n = 7) showed reproducible increases in RL (C1, delta RL = 15.1 +/- 2.7 cm H2O X 1(-1) X s; C2, delta RL = 15.7 +/- 3.0; C3, delta RL = 13.1 +/- 2.9; mean +/- 1 SE). After parasympathectomy there was an increase in responsiveness after C3 (C1, delta RL = 15.0 +/- 4.3; C2, delta RL = 16.4 +/- 6.4; C3, delta RL = 29.9 +/- 11.6; p less than 0.01). Sympathectomy and vagosympathectomy did not significantly alter responsiveness. The results suggest that vagally mediated inhibitory influences modulate the bronchial response to aerosolized methacholine in the cat.

Aerosols↗

Effect of intravenous epinephrine on uterine artery blood flow velocity in the pregnant guinea pig.

The purpose of the present study was to determine the effect of intravenously administered epinephrine on the maternal cardiovascular response and uterine artery blood flow velocity (UBFV) in the pregnant guinea pig. Epinephrine (0.2, 0.5, and 1.0 micrograms/kg) and lidocaine (0.4 mg/kg, with and without 0.2 micrograms/kg of epinephrine) were administered intravenously to seven chronically instrumented pregnant guinea pigs near term. Lidocaine without epinephrine did not significantly alter maternal heart rate (MHR), maternal mean arterial pressure (MMAP), or UBFV. Epinephrine, with and without lidocaine, resulted in a transient decrease in MHR. Further, epinephrine, with and without lidocaine, resulted in significant elevations in MMAP and significant, dose-related reductions in UBFV. Mean (+/- SEM) UBFV was 72 +/- 4%, 56 +/- 4%, and 40 +/- 5% of baseline at 30 s after administration of epinephrine, 0.2, 0.5, and 1.0 micrograms/kg, respectively. It is concluded that these small intravenous boluses of epinephrine result in significant, although transient, reductions in UBFV in the pregnant guinea pig.

Animals↗

Acetylcholine release from canine isolated airway is not modulated by norepinephrine.

We measured acetylcholine (ACh) release from canine isolated tracheal smooth muscle (TSM) and bronchial spirals using a radioenzymic assay technique. Tissue was incubated in physiological salt solution containing physostigmine (3.10(-5) M), atropine (10(-7) M), and choline (5.10(-6) M), and bath fluid was collected every 15 min for assay. There was a resting release of ACh of 209 +/- 44 pmol/g tissue (mean +/- SE) from 53 to 77 specimens of TSM. Electrical field stimulation (ES) increased ACh release, which was blocked by tetrodotoxin (10(-6) g/ml), confirming the neural origin of ACh. The ACh output during ES (2-ms pulses) at 10 Hz increased linearly from 188 +/- 50 pmol/g tissue (mean +/- SE) for a 1-min volley, to 323 +/- 57 for three volleys, and 544 +/- 128 for five volleys. The ACh output/pulse was constant during ES at 20, 15, 10, and 5 Hz, but it was significantly higher at 2 than at 5 Hz (P less than 0.005). Incubation of TSM with norepinephrine (NE, 10(-5) M) did not affect ACh output either at 2 or 10 Hz. Likewise, ACh output from bronchial spirals during ES and 2 Hz was unaffected by NE. In contrast, NE treatment of isolated guinea pig ileum reduced the ACh released by ES at 2 Hz to 40 +/- 7% (P less than 0.001) of the control ACh output. It is concluded that evoked release of ACh (output/pulse) from cholinergic nerves in canine airway is frequency dependent, as in guinea pig ileum, but that, unlike guinea pig ileum, NE does not modulate its release.

Acetylcholine↗

Methacholine-induced airway reactivity of inbred rats.

Dose-response curves to inhaled aerosolized methacholine chloride (MCh) were obtained in anesthetized spontaneously breathing rats. Thirty rats (10/strain), randomly selected from highly inbred ACI, Lewis (L), and Brown Norway (BN) strains and 40 rats (20/strain) from similarly inbred Wistar-Furth (WF) and Buffalo (Buf) strains were studied. Airway responses were quantitated from changes in pulmonary resistance (RL) and airway reactivity was calculated as the dose of MCh required to increase RL to 150% (ED150RL) and 200% (ED200RL) of base line. There were no statistically significant differences in ED150RL and ED200RL among the five rat strains. Large interindividual variability was present as evidenced by 128-fold differences in ED150RL and ED200RL between the least and most sensitive animal of the same strain. In contrast, seven animals studied repeatedly on different days had values of ED150RL that differed by an average of only 2.9-fold (range 1.6-5.3). Thirteen rats that were studied on two occasions separated by an interval of 3 mo showed no systematic changes in airway reactivity. We conclude that airway reactivity to inhaled methacholine in anesthetized nose-breathing rats is not strain related, and despite animals of a given strain being genetically identical, the variability in airway reactivity within strains suggests that environmental rather than genetic factors are the major determinants of that reactivity.

Airway Resistance↗

The effects of parasympathectomy on serotonin-induced bronchoconstriction in the cat.

We studied the contribution of neural influences, in particular, the nonadrenergic, noncholinergic inhibitory system, on the modulation of airway responses to serotonin (5-HT) in the anesthetized and mechanically ventilated cat. Airway responses were assessed by measurement of pulmonary resistance (RL). Parasympathectomy (PS) caused a variable increase in bronchoconstriction in 9 of 10 cats (n = 10) that had received pretreatment intravenously with atropine (3 mg/kg) and propranolol (2 mg/kg); PS performed following pretreatment with phentolamine (2 mg/kg), propranolol, and atropine led to an increase in bronchoconstriction in only 2 of 6 cats. Dose-response curves to aerosolized 5-HT were performed in one group of cats (n = 5) before and 30 min after PS and in control group (n = 6). Both groups of animals were pretreated intravenously with atropine, propranolol, and phentolamine. The concentration of aerosolized 5-HT that was necessary to double pulmonary resistance (ED200RL) was significantly reduced from 0.117 to 0.062 mg/ml (p less than 0.01) by PS, in contrast to control cats in which ED200RL during 2 consecutive dose-response curves (0.076 and 0.087 mg/ml, respectively) did not change significantly. We conclude that there is neural modulation of airway responses to infused 5-HT through an alpha-adrenergic pathway and that an additional inhibitory nonadrenergic, noncholinergic neural influence is demonstrable in the response to aerosolized 5-HT.

Aerosols↗

Central and local cholinergic components of histamine-induced bronchoconstriction in dogs.

To determine the importance of central and local reflexes in the bronchoconstriction produced by inhaled aerosolized histamine, chloralose-urethan-anesthetized dogs were intubated with a double-lumen catheter, ventilated with a dual cylinder respirator, and instrumented for the measurements of pulmonary conductance (GL) and dynamic compliance (Cdyn) in each lung. In each dog, dose-response curves to inhaled aerosolized histamine were obtained in both lungs separately but synchronously. Four series of experiments were performed. In the first series (n = 10) the responses of the right and left lungs were compared and found to be approximately equal, indicating that one lung could be used as a control for the other. In the second and third series the dose-response curve of one lung that had either been treated with inhaled atropine sulfate (n = 6) (4 mg/ml) or vagotomized (n = 4) was compared with the contralateral control lung. At low concentrations of histamine, GL and Cdyn decreased more in the control lungs than in their atropine-treated or vagotomized counterparts, and approximately 40% of the bronchoconstriction induced was reflex in origin. At higher concentrations of histamine the responses of the control and atropine-treated or vagotomized lungs were not significantly different. In the fourth series of experiments (n = 6) histamine dose-response curves were obtained following combined bilateral vagotomy and unilateral delivery of inhaled aerosolized atropine. In these dogs GL, but not Cdyn, fell to a greater extent in the control than in the atropine-treated lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of mechanical loading on displacements of chest wall during breathing in humans.

Using a respiratory inductive plethysmograph (Respitrace) we studied thoracoabdominal movements in eight normal subjects during inspiratory resistive (Res) and elastic (El) loading. The magnitude of loads was chosen so as to produce a fall in inspiratory mouth pressure of 20 cmH2O. The contribution of rib cage (RC) to tidal volume (VT) increased significantly from 68% during quiet breathing (QB) to 74% during El and 78% during Res. VT and breathing frequency did not change significantly. During loading a phase lag was present on inspiration so that the abdomen led the rib cage. However, outward movement of the abdomen ceased in the latter part of inspiration, and the RC became the sole contributor to VT. These observations suggest greater recruitment of the inspiratory musculature of the RC than the diaphragm during loading, although changes in the mechanical properties of the chest wall may also have contributed. Indeed, an increase in abdominal end-expiratory and end-inspiratory pressures was observed in five out of six subjects, indicating abdominal muscle recruitment which may account for part of the reduction in abdominal excursion. Both Res and El increased the rate of emptying of the respiratory system during the ensuing unloaded expiration as a result of a reduction in rib cage expiratory-braking mechanisms. The time course of abdominal displacements during expiration was unaffected by loading.

Abdominal Muscles↗