Variability of airway responses to inhaled histamine in normal subjects

1979 ◽  
Vol 47 (1) ◽  
pp. 51-58 ◽  
Author(s):  
M. P. Habib ◽  
P. D. Pare ◽  
L. A. Engel
Keyword(s):  
Dose Response ◽  
Lung Volume ◽  
Normal Population ◽  
Normal Subjects ◽  
Beta Blockade ◽  
Forced Expiration ◽  
Response Curves ◽  
Double Blind ◽  
Dose Response Curves ◽  
Airway Responses

Dose-response curves to inhaled histamine were studied in 12 normal subjects. Pulmonary resistance (RL) and dynamic compliance (Cdyn) were measured during tidal breathing, and maximum expiratory flow rates, at an absolute lung volume corresponding to 40% of control vital capacity, were obtained during forced expiration from tidal end inspiration (Vmax40p) and from total lung capacity (Vmax40c). Threshold was defined as the histamine dose at which a departure from the range of normal measurements was observed. RL and Vmax40p indicated lowest threshold values, which varied by a factor of 32 and 38, respectively. There was no correlation between reactivity, which reflects the slope of the dose-response curve beyond the threshold dose, and threshold doses, nor between the initial RL (normalized for lung volume) and either threshold or reactivity. In eight subjects, restudied on two occasions after 10 mg propranolol or after saline, injected in a double-blind manner, there was no change in the dose-response curves. These results indicate that different indices of bronchoconstriction may yield different dose-response curves and hence different sensitivities. In addition, a wide variation of airway responses to inhaled histamine exists in the normal population and beta-blockade does not influence this variability.

scholarly journals Acute Effects of Triiodothyronine on Endothelial Function in Human Subjects

2007 ◽  
Vol 92 (1) ◽  
pp. 250-254 ◽  
Author(s):  
Raffaele Napoli ◽  
Vincenzo Guardasole ◽  
Valentina Angelini ◽  
Emanuela Zarra ◽  
Daniela Terracciano ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Controlled Trial ◽  
University Hospital ◽  
Acute Effects ◽  
Response Curves ◽  
Double Blind ◽  
Low T3 ◽  
Dose Response Curves

Abstract Context: Thyroid hormone regulates several cardiovascular functions, and low T3 levels are frequently associated with cardiovascular diseases. Whether T3 exerts any acute and direct effect on endothelial function in humans is unknown. Objective: Our objective was to clarify whether acute changes in serum T3 concentration affect endothelial function. Design, Setting, and Subjects: Ten healthy subjects (age, 24 ± 1 yr) participated in a double-blind, placebo-controlled trial at a university hospital. Interventions: T3 (or placebo) was infused for 7 h into the brachial artery to raise local T3 to levels observed in moderate hyperthyroidism. Vascular reactivity was tested by intraarterial infusion of vasoactive agents. Main Outcome Measures: We assessed changes in forearm blood flow (FBF) measured by plethysmography. Results: FBF response to the endothelium-dependent vasodilator acetylcholine was enhanced by T3 (P = 0.002 for the interaction between T3 and acetylcholine). The slopes of the dose-response curves were 0.41 ± 0.06 and 0.23 ± 0.04 ml/dl·min/μg in the T3 and placebo study, respectively (P = 0.03). T3 infusion had no effect on the FBF response to sodium nitroprusside. T3 potentiated the vasoconstrictor response to norepinephrine (P = 0.006 for the interaction). Also, the slopes of the dose-response curves were affected by T3 (1.95 ± 0.77 and 3.83 ± 0.35 ml/dl·min/mg in the placebo and T3 study, respectively; P < 0.05). The increase in basal FBF induced by T3 was inhibited by NG-monomethyl-l-arginine. Conclusions: T3 exerts direct and acute effects on the resistance vessels by enhancing endothelial function and norepinephrine-induced vasoconstriction. The data may help clarify the vascular impact of the low T3 syndrome and point to potential therapeutic strategies.

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

1987 ◽  
Vol 62 (3) ◽  
pp. 1324-1330 ◽  
Author(s):  
D. J. Ding ◽  
J. G. Martin ◽  
P. T. Macklem
Keyword(s):  
Dose Response ◽  
Lung Volume ◽  
Normal Subjects ◽  
Smooth Muscle Contraction ◽  
Base Line ◽  
Pulmonary Resistance ◽  
Response Curves ◽  
Maximum Value ◽  
Residual Capacity ◽  
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.

Tachyphylaxis to inhaled aerosolized histamine in anesthetized dogs

1985 ◽  
Vol 59 (5) ◽  
pp. 1355-1363 ◽  
Author(s):  
S. Shore ◽  
J. G. Martin
Keyword(s):  
Dose Response ◽  
Dynamic Compliance ◽  
Pulmonary Mechanics ◽  
Base Line ◽  
Response Curves ◽  
Low Concentrations ◽  
Anesthetized Dogs ◽  
Dose Response Curves ◽  
High Concentrations ◽  
Airway Responses

Three consecutive dose-response curves to inhaled aerosolized histamine, separated by 1-h intervals, were obtained in 20 anesthetized mongrel dogs. In general, successive histamine dose-response curves shifted progressively rightward. Changes in pulmonary resistance (RL) and dynamic compliance (Cdyn) in response to low concentrations of histamine were reproducible, but responses to high concentrations (sufficient to at least double RL or decrease Cdyn by at least 30%) decreased on successive dose-response curves. The concentration of histamine required to double RL increased significantly (P less than 0.05) from 1.01 mg/ml on the first to 1.62 and 2.02 mg/ml on the second and third dose-response curves. In contrast, consecutive methacholine dose-response curves were not significantly different. Indomethacin pretreatment (5 mg/kg iv) prevented histamine tachyphylaxis, whereas atropine (4 mg iv) did not. However, indomethacin did not alter base-line pulmonary mechanics or histamine responsiveness as measured on the first dose-response curve. We conclude that tachyphylaxis to inhaled aerosolized histamine occurs in anesthetized dogs. Our results are consistent with an important role for endogenous prostaglandins in modulating the airway responses to repeated histamine exposures.

Methacholine dose-response curves in normal and asthmatic man: Effect of starting conductance and pharmacological antagonism

1984 ◽  
Vol 66 (6) ◽  
pp. 665-673 ◽  
Author(s):  
K. F. Chung ◽  
P. D. Snashall
Keyword(s):  
Dose Response ◽  
Normal Subjects ◽  
Small Degree ◽  
Response Curves ◽  
Significant Difference ◽  
Positive Linear Correlation ◽  
Dose Response Curves ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Different Doses

1. The bronchial response of 11 normal and ten stable asthmatic subjects to increasing concentrations of methacholine aerosol was assessed by serial measurements of specific airways conductance (scaw) in a body plethysmograph. 2. Cumulative log dose-response curves were constructed. The threshold provocative dose of methacholine needed to cause a 35% fall in starting sCaw (pD35) and the steepest slope of the response were measured from each curve. 3. On separate days subjects were premedicated with 0.9% NaCl solution (control) in duplicate, chlorpheniramine, salbutamol and atropine, the last-named at two different doses, one twice the other. 4. Asthmatic subjects had a lower mean PD35 and a lower mean slope than normal subjects. 5. Pretreatment with salbutamol resulted in a greater increase in sGaw than after atropine but caused a smaller increase in PD35 in both groups. There was a dose-dependent increase in PD3s after the two doses of atropine, but no significant difference in bronchodilatation between doses. Mean steepest slope approximately doubled in these three sets of challenges. 6. Chlorpheniramine caused a small degree of bronchodilatation and there was a non-significant increase in mean PD3s and in mean steepest slope in both normal and asthmatic groups. 7. There was a positive linear correlation between starting sGaw and steepest slope in each group of premedicated challenges, such that when

The Effects of Melatonin Premedication on Propofol and Thiopental Induction Dose???Response Curves: A Prospective, Randomized, Double-Blind Study

2006 ◽  
Vol 103 (6) ◽  
pp. 1448-1452 ◽  
Author(s):  
Mohamed Naguib ◽  
Abdulhamid H. Samarkandi ◽  
Mohamed A. Moniem ◽  
Emad El-Din Mansour ◽  
Ahmad A. Alshaer ◽  
...  
Keyword(s):  
Dose Response ◽  
Blind Study ◽  
Double Blind Study ◽  
Response Curves ◽  
Double Blind ◽  
Induction Dose ◽  
Dose Response Curves

Enhanced airway responses to substance P after repeated challenge in guinea pigs

1989 ◽  
Vol 66 (2) ◽  
pp. 955-961 ◽  
Author(s):  
S. A. Shore ◽  
J. M. Drazen
Keyword(s):  
Substance P ◽  
Dose Response ◽  
Guinea Pigs ◽  
Response Curve ◽  
Enzyme Inhibitor ◽  
Dose Response Curve ◽  
Base Line ◽  
Response Curves ◽  
Dose Response Curves ◽  
Airway Responses

We performed three consecutive dose-response curves to rapid intravenous infusions of substance P (SP) in anesthetized, mechanically ventilated guinea pigs. The dose of SP required to decrease pulmonary conductance to 50% of its base-line value (ED50GL) decreased 2.8-fold (P less than 0.002) and 3.3-fold (P less than 0.001) on the second and third dose-response curves, respectively, compared with the first. SP did not alter airway responses to intravenous histamine but did cause a significant (3.7-fold) decrease in ED50GL for dose-response curves to intravenous capsaicin, an agent that causes bronchoconstriction by release of endogenous tachykinins. The neutral metalloendopeptidase inhibitor thiorphan (0.5 mg) and the angiotensin-converting enzyme inhibitor captopril (1.7 mg) both caused a marked enhancement of airway responses to SP observed on the first dose-response curve but did not alter the enhancement of SP-induced airway responses produced by repeated SP challenge. The anticholinergic atropine (5 mg/kg iv), the antihistamine mepyramine (8 mg/kg iv), and the cyclooxygenase inhibitor indomethacin (30 mg/kg ip) had no effect on the first SP dose-response curve. Atropine and mepyramine did not prevent the enhancement of SP responses observed with repeated challenge, but after pretreatment with either indomethacin or acetylsalicylic acid, dose-response curves to SP were reproducible. Our results indicate that airway responses to intravenous SP are enhanced with repeated SP challenge and suggest that cyclooxygenase products of arachidonic acid metabolism are involved in the mediation of this phenomenon.

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

1980 ◽  
Vol 48 (5) ◽  
pp. 789-793 ◽  
Author(s):  
W. M. Abraham ◽  
A. J. Januszkiewicz ◽  
M. Mingle ◽  
M. Welker ◽  
A. Wanner ◽  
...  
Keyword(s):  
Dose Response ◽  
Airway Hyperreactivity ◽  
Base Line ◽  
Response Curves ◽  
Pulmonary Flow ◽  
Short Term Exposure ◽  
Significant Depression ◽  
Dose Response Curves ◽  
Airway Responses ◽  
Conscious Sheep

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.

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