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Biomedical subjects

S H Loring

Publications and source records attributed to S H Loring.

At least 73 records · Page 4Linked to original sources
PubMed1981

Effects of beta adrenergic blockade on histamine and prostaglandin-F2 alpha responsiveness in the dog.

To examine whether either the degree of existing beta adrenergic tone or the magnitude of beta adrenergic response during bronchoconstriction might account for the differences that exist between dogs in their pulmonary responsiveness to aerosol challenge with bronchoconstrictor agents, dose-response curves were performed in a group of dogs to either histamine or prostaglandin-F2 alpha, both before beta blockade with propranolol. Beta blocked had no significant effect on control values of dynamic compliance (Cdyn) or resistance of the lung (RL) or on pulmonary responsiveness to prostaglandin f2 alpha. Although propranolol did not have a significant effect on aerosol responsiveness to histamine for the group of dogs taken together, those dogs initially least responsive to aerosol histamine did become more responsive after beta blockade. This effect of beta blockade was statistically significant only for Cdyn and not for RL, suggesting enhancement of peripheral airway effects. We conclude that a beta adrenergic mechanism may contribute to the range of responsiveness found among dogs in their pulmonary responsiveness to histamine but that other as yet undefined factors must also contribute to the differences that exist among dogs in their pulmonary responsiveness to bronchoconstrictor agents.

Adrenergic beta-Antagonists↗
PubMed1981

Direct and reflex bronchoconstriction induced by histamine aerosol inhalation in dogs.

Histamine aerosols were administered to nine anesthetized, paralyzed, mechanically ventilated mongrel dogs with the cervical vagi first intact, then sectioned, and then peripherally stimulated at two intensities. Pulmonary resistance (RL) was measured, and dose-response curves were constructed in the four conditions. All dogs had dose-related increases in RL with increasing histamine aerosol concentrations. After the vagi were cut, the degree to which constant levels of vagal stimulation altered the dose-response relationships was assessed by examining the slopes and positions of the RL vs. histamine curves. Four of the nine animals studied showed evidence of increasing vagal efferent activity as the concentration of histamine in the aerosol increased, but three did not. Two of the dogs had equivocal responses in that increasing activity was suggested but not clearly demonstrated. These results indicate that, in addition to direct effects of histamine, the extent of and basis for vagal interaction with this stimulus varies among dogs. The results suggest that the basis of vagal interaction is related to either constant efferent activity (tone) or increasing efferent activity (reflexes).

Aerosols↗
PubMed1981

Serial distribution of bronchoconstriction induced by vagal stimulation or histamine.

We compared the relative site of airway responses with histamine aerosol and electrical stimulation of the vagi in dogs that were anesthetized, vagotomized, mechanically ventilated, and treated with propranolol. We made measurements of pulmonary resistance by forced oscillations and of dead-space volume as indirect indicators of airway size. Direct measures of airway size were obtained from radiographic bronchograms and from acoustically equivalent airway areas as a function of distance, computed from pulse response data. During vagal stimulation there were marked increases in pulmonary resistance, decreases in dead space, and reduction in acoustic cross-sectional area at all distances. In contrast, after inhalation of enough aerosol histamine to increase pulmonary resistance approximately as much as it did during vagal stimulation, we observed little ro no reduction in dead space and reductions in acoustic cross-sectional area that were most marked in distal airways. The findings were confirmed by the radiographic bronchograms and are consistent with observations reported by others. These observations confirm previous data and demonstrate the utility of this technique for in vivo measurements.

Airway Resistance↗
PubMed1981

Vagal stimulation and aerosol histamine increase hysteresis of lung recoil.

Bronchoconstriction changes pulmonary resistance and dynamic compliance by altering both airway properties and dynamic lung tissue recoil. To assess the contribution of recoil, we measured transpulmonary pressure in anesthetized open-chest dogs during sinusoidal ventilation with gas flow and during sinusoidal compression of intrapulmonary gas without flow. Measurements with gas flow characterized total pulmonary behavior, including the contribution of gas flow in airways, whereas measurements during gas compression characterized lung tissue recoil alone. Histamine aerosol produced a 54% decrease in dynamic compliance, a 465% increase in total pulmonary resistance, and a 153% increase in pressure-volume hysteresis of dynamic recoil. Vagal stimulation produced a 31% decrease in dynamic compliance, a 135% increase in total pulmonary resistance, an 82% increase in the hysteresis of recoil, and a 15% increase in mean recoil pressure. At slow oscillation frequencies (0.2 Hz) and high transpulmonary pressures (10 cmH2O), hysteresis of lung recoil contributes substantially to total pulmonary resistance, and changes in dynamic lung recoil can account for much (35%) of the increase in pulmonary resistance seen with bronchoconstriction.

Aerosols↗
PubMed1981

Effects of lung inflation on airway and tissue responses to aerosol histamine.

The pulmonary effects of aerosol histamine exposure include an increase in pulmonary resistance (RL) and a decrease in dynamic compliance (Cdyn). These changes are substantially reversed by inflation of the lungs to 30 cmH2O transpulmonary pressure (TLC). Although histamine has been shown to change both the airway and tissue components of RL and Cdyn, it is not known whether lung inflation reverses the changes in airways, in tissue, or in both. We studied six anesthetized, paralyzed, open-chest dogs. We sequentially measured RL and Cdyn during oscillations in lung volume at 0.6 Hz with the airway open and during compression-decompression of the lungs without tracheal airflow. In the control state after saline aerosol, inflation to TLC resulted in a slight increase in compliance and a decrease in the tissue component of RL. Aerosol histamine exposure caused an increase in resistance and a decrease in compliance due to both airway and tissue changes. Inflation of the lungs to TLC largely reversed the changes due to airway constriction without consistently affecting the changes due to tissue. We conclude that after histamine exposure smooth muscle responsible for airway narrowing is stretched by lung inflation but that contractile elements responsible for alterations in air-space distensibility and hysteresis of dynamic lung recoil are either not stretched by lung inflation or are stretched and shorten again rapidly.

Aerosols↗
PubMed1981

Regional differences in abdominal muscle activity during various maneuvers in humans.

To determine if regional differences exist in the activity of abdominal muscles during respiratory and nonrespiratory maneuvers, we studied four healthy subjects by comparing electromyographic (EMG) activity from surface electrodes placed lateral to rectus muscle, one pair on the upper abdomen and the other on the lower abdomen. In one subject EMG recordings were made from wires placed in various layers of the abdominal wall. Relative positions and changes in size of anatomic structures during maneuvers were determined from real-time ultrasonography of the abdominal wall. Expulsive or valsalva maneuvers evoked the same relative EMG activity in the upper and lower abdomen. In the resting supine posture no EMG activity was detectable; however, in the standing posture greater tonic EMG activity appeared in the lower abdomen. During rebreathing, phasic EMG activity during expiration was greater in the upper than in the lower abdomen in all subjects. Observations from ultrasonographic and electromyographic evaluations suggest that the control of abdominal muscles and their influence on respiratory mechanics are potentially more complex than has been suggested by previous reports.

Abdominal Muscles↗
PubMed1981

Effects of frequency, tidal volume, and lung volume on CO2 elimination in dogs by high frequency (2-30 Hz), low tidal volume ventilation.

Recent studies have shown that effective pulmonary ventilation is possible with tidal volumes (VT) less than the anatomic dead-space if the oscillatory frequency (f) is sufficiently large. We systematically studied the effect on pulmonary CO2 elimination (VCO2) of varying f (2-30 Hz) and VT (1-7 ml/kg) as well as lung volume (VL) in 13 anesthetized, paralyzed dogs in order to examine the contribution of those variables that are thought to be important in determining gas exchange by high frequency ventilation. All experiments were performed when the alveolar PCO2 was 40 +/- 1.5 mm Hg. In all studies, VCO2 increased monotonically with f at constant VT. We quantitated the effects of f and VT on VCO2 by using the dimensionless equation VCO2/VOSC = a(VT/VTo)b(f/fo)c where: VOSC = f X VT, VTo = mean VT, fo = mean f and a, b, c, are constants obtained by multiple regression. The mean values of a, b, and c for all dogs were 2.12 X 10(-3), 0.49, and 0.08, respectively. The most important variable in determining VCO2 was VOSC; however, there was considerable variability among dogs in the independent effect of VT and f on VCO2, with a doubling of VT at a constant VOSC causing changes in VCO2 ranging from -13 to +110% (mean = +35%). Increasing VL from functional residual capacity (FRC) to the lung volume at an airway opening minus body surface pressure of 25 cm H2O had no significant effect on VCO2.

Animals↗
PubMed1980

Effective pulmonary ventilation with small-volume oscillations at high frequency.

At high oscillation frequencies (4 to 30 hertz), effective alveolar ventilation can be achieved with tidal volumes much smaller than the anatomic dead space. An explanation of this phenomenon is given in terms of the combined effects of diffusion and convection and in terms of data consistent with the hypothesis. Theory and experimental results both show that the significant variable determining the effectiveness of gas exchange is the amplitude of the oscillatory flow rate independent of the individual values of frequency and stroke volume.

Animals↗
PubMed1980

In vivo effect of cimetidine on canine pulmonary responsiveness to aerosol histamine.

A series of experiments were designed to discover whether pulmonary histamine H2 receptors might be of physiologic importance in vivo in the dog. Dose-response curves were performed to aerosol histamine in 11 dogs both before and 1 hr after H2 receptor blockade with cimetidine (1 mg/kg as a rapid intravenous infusion). Cimetidine had no significant effect on control values of dynamic compliance or resistance of the lung. In the 11 dogs tested H2 receptor antagonism significantly potentiated (p less than 0.05) the animals' pulmonary responsiveness to aerosol histamine. The potentiation of histamine constrictor e-fects produced by cimetidine were more marked on those dogs initially least responsive to aerosol histamine (p less than 0.01). We have found evidence for the presence of inhibitory H2 receptors in canine airways and for the distribution of these receptors among dogs, explaining in part the previously described differences among dogs in the pulmonary responsiveness to aerosol histamine.

Aerosols↗
PubMed1980

Lung recoil during rapid vital capacity expirations simulated by gas compression.

Excised dog lobes were inflated to a transpulmonary pressure (PL) of about 30 cmH2O, and their airways were occluded. Then they were rapidly compressed to a volume where PL was about zero, simulating forced expiratory maneuvers. Since there was no airflow during the compression, PL was a direct measure of lung recoil. Lung volume (VL) was calculated from absolute airway pressure using Boyle's law. At ambient temperature, lung recoil pressure during compressive maneuvers simulating forced vital capacity expirations (Pdyn) was less than that during quasi-static (30 s) compressions (Pst). Typically the dynamic component (i.e., Pst--Pdyn) decreased from about 2 cmH2O near total lung capacity to no difference at the end of the compression. Cooling the lobes to 15 degrees C increased Pst-Pdyn, and warming the lobes to 37 degrees C reduced Pst-Pdyn almost to zero. We suggest that the driving force of lung recoil during expirations is adequately modeled by the quasi-static VL/PL relationship, though a small correction should be made for excised lungs at room temperature.

Airway Resistance↗
PubMed1980

Comparison of the responsiveness to histamine and to Ascaris suum challenge in dogs.

The pulmonary and dermal sensitivity of a group of mongrel dogs to an extract of Ascaris suum protein was compared with the pulmonary and dermal sensitivity to histamine in this same group. We found a modest but significant correlation in the entire population between skin test reaction to histamine and to A. suum protein (r = 0.52, p < 0.05), but when the skin test results were compared with those of aerosol challenge, no significant correlation was found. However, when those dogs with reactions to histamine challenge that fell within a narrow range were considered as a separate group, there was a significant correlation between the reactions of aerosol challenge with A. suum and those of the skin tests with A. suum (r = 0.56, p < 0.025). These findings were consistent with the hypothesis that aerosol bronchoconstrictor responsiveness and immunologic responsiveness are separate attributes that combine to determine airway responsiveness to a specific antigen.

Animals↗
PubMed1979

Vagal effects on histamine, carbachol, and prostaglandin F2 alpha responsiveness in the dog.

To investigate whether an individual dog's responsiveness to histamine correlates with its responsiveness to other bronchoconstrictor agents and to investigate whether varying vagal effects account for the previously described range of histamine responsiveness, we compared dose-effect relationships of histamine to those of two pharmacological dissimilar agents, carbachol and prostaglandin F2 alpha before and after vagal blockade. There was a highly significant correlation between histamine and both carbachol (P less than 0.001) and prostaglandin F2 alpha (P less than 0.001) responsiveness. The range of responsiveness to prostaglandin F2 alpha was greater than that for histamine or carbachol. When histamine and carbachol were given simultaneously, a purely additive effect was found. Vagal blockade had no significant effect on histamine or carbachol responsiveness, but significantly diminished the responsiveness to prostaglandin F2 alpha; however, it neither narrowed the range nor changed the rank order of responsiveness. We conclude that the range of responsiveness is not specific for any one agent and that vagal mechanisms do not play a role in producing this range.

Airway Resistance↗
PubMed1978

Distribution of pulmonary responsiveness to aerosol histamine in dogs.

Dose-response curves to aerosol histamine in 102 anesthetized, intubated, spontaneously breathing dogs revealed a spectrum of airway responsiveness with a greater than 40-fold difference between the most and the least sensitive animals. The frequency distribution of responses fits a log normal distribution. No correlation was found between sex, age, or control values of dynamic compliance (Cdyn) and lung resistance (RL) and the dose of histamine required to cause a response. Repetitive studies in 17 dogs observed for up to 20 mo showed that the dose at which an individual dog would respond was reproducible within a narrow range and that the differences between dogs were highly significant (P greater than 0.001). The long-term reproducibility of the response to aerosol histamine in individual dogs suggests that short-term reversible airway insults are not responsible for the range in responses noted between animals.

Aerosols↗
PubMed1978

Vagal and aerosol histamine interactions on airway responses in dogs.

Histamine aerosol was administered to 10 anesthetized paralyzed artificially ventilated dogs whose vagi were first intact, then cut, and then peripherally stimulated. Pulmonary resistance (RL) was measured and dose-response curves determined in the three conditions. The dogs were divided into two groups based on the initial response to histamine with the vagi intact. The low-dose (LD) group had a greater than or equal to 50% increase in RL when exposed to a histamine concentration of 1.0 mg/ml. The high-dose (HD) group had a greater than or equal to 50% increase in RL when exposed to an aerosol containing 3.0 mg/ml histamine or more. In both groups there was a dose-related increase in RL with histamine with the vagi intact, cut, or stimulated. In three of the LD dogs there was a greater than additive interaction between vagal stimulation and inhaled histamine, whereas in the HD dogs the interaction was at most additive. With the vagi cut, both groups had a significantly lesser histamine response. The results show that differences in histamine responsiveness between dogs is in part related to varying degrees of nonreflex histamine-vagal interaction.

Aerosols↗
PubMed1978

Lung volumes after antigen infusion in the guinea pig in vivo: effects of vagal section.

The effects of intravenous antigen infusion on lung volumes and quasi-static deflationary pulmonary compliance in guinea pigs previously sensitized to ovalbumin were studied in vivo. Ovalbumin infusion significantly increased minimal gas volume to a similar extent in animals with intact or cut vagi. Total lung capacity fell only in animals with intact vagi. Quasi-static compliance fell in both groups of animals, but the fall was significantly greater in animals with intact vagi. These data demonstrate that immediate hypersensitivity reactions alter lung volumes and the elastic properties of the lung by both vagal dependent and vagal independent mechanisms.

Animals↗
PubMed1977

Canine pulmonary response to aerosol histamine: direct versus vagal effects.

Histamine, a potent bronchoconstrictor, has been shown to produce bronchoconstriction both directly and by a vagal reflex. To define the relative roles of direct and reflex effects, we studied the pulmonary response of dogs exposed to increasing doses of aerosol histamine before and after vagal blockade or vagotomy. In addition, the relative contributions of aerodynamically large and small airways to the overall response were determined by the measurement of pulmonary resistance on sulfur hexafluoride-oxygen and helium-oxygen mixtures. Histamine aerosol caused a similar dose-dependent increase in resistance of aerodynamically large and small airways and fall in dynamic compliance. The dose-response relationships were not consistently altered by either vagal blockade or vagotomy. The following variables were found not to alter the experimental results: anesthesia, type of aerosol generator, control of breathing during aerosol exposure, spontaneous breathing vs. controlled ventilation after aerosol exposure, cold block of vagi vs. vagotomy. We conclude that 1) histamine aerosol in dogs causes a local dose-dependent constriction of bronchial smooth muscle, and 2) the vagus nerve played a relatively minor role in the pulmonary response to aerosol histamine in these experiments.

Aerosols↗