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Perfused bronchial segment and bronchial strip: narrowing vs. isometric force by mediators
H W Mitchell1, K E Willet, M P Sparrow
1Department of Physiology, University of Western Australia, Nedlands.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|June 1, 1989
Summary
Airway closure in bronchial segments occurs before maximal muscle activation when constant pressure is applied, affecting drug responses. This contrasts with constant flow perfusion, revealing differences in carbachol and histamine sensitivity.
Area of Science:
- Pulmonary Physiology
- Pharmacology
- Respiratory System Mechanics
Background:
- Bronchial smooth muscle tone regulates airway caliber.
- Understanding drug effects on airway constriction is crucial for respiratory disease management.
Purpose of the Study:
- To investigate the impact of different perfusion methods (constant pressure vs. constant flow) on the contractile responses of bronchial segments to carbachol and histamine.
- To compare the sensitivity and maximal response of bronchial smooth muscle under varying experimental conditions.
Main Methods:
- Bronchial segments and strips were used to measure muscle shortening and force.
- Perfusion studies were conducted at constant pressure (5-6 cmH2O) and constant flow.
- Concentration-response curves for carbachol and histamine were generated to determine sensitivity (EC50) and maximal effect (Emax).
Main Results:
- Under constant pressure perfusion, airway resistance increased exponentially with carbachol and histamine, with linear pressure-flow relationships.
- Both agents caused muscle shortening, but maximal isometric force and isotonic shortening were greater with carbachol than histamine in bronchial strips.
- Sensitivity (EC50) to carbachol and histamine was significantly reduced (more than tenfold) in segments perfused at constant flow compared to strips.
- Constant pressure perfusion led to airway closure before maximal pharmacological activation.
Conclusions:
- Airway closure is a critical factor influencing observed drug responses in perfused bronchial segments under constant pressure.
- Experimental conditions, specifically perfusion method, significantly alter the apparent sensitivity and maximal contractile response of bronchial smooth muscle to agonists.
- Findings highlight the importance of considering experimental setup when extrapolating in vitro data to in vivo airway function.