Document Detail

Agonist-mediated airway challenge: cardiopulmonary interactions modulate gas exchange and recovery.
MedLine Citation:
PMID:  15705534     Owner:  NLM     Status:  MEDLINE    
Diverse agonists used for airway challenges produce a stereotypic sequence of immediate functional responses (e.g., bronchoconstriction, gas trapping, hypoxemia, etc.) at the time such reactions are triggered. The reaction incorporates both pulmonary and cardiac changes that clearly interact in an orchestrated fashion taking the subject (or animal model) through the response generally to ultimate recovery. We hypothesize that despite differences in the initiation of the response, diverse airway provocations lead to a cascade of events that converge through a common physiologic pathway. To better understand the sequence of events and the counterbalanced cardiopulmonary responses, we examined histamine, methacholine, and ovalbumin (OVA) challenges in the awake guinea pig model and assessed ventilatory and breathing mechanics in the context of associated cardiac parameters. With the histamine response as the prototype, we evaluated the role of beta-adrenoreceptors using propranolol (1.0-10 mg/kg i.p.) and found that beta-adrenoreceptors are critical in reducing challenge-induced gas trapping in the lungs. The disposition of the circulatory response to agonist challenge (the OVA model) was reflected in a significant absolute shunting of blood through poorly ventilated regions of the lung. The methacholine challenge revealed that gasping enhanced lung inflation and reversed the diminished Pa(O2). Moreover, beta-sympathetic function was critical to recovery. Collectively, the response profiles of these disparate models of airway challenge suggest a highly integrated balance to maintain gas exchange among the pulmonary airways and vasculature, modulated in recovery by beta-adrenoreceptors.
Mildred J Wiester; Daniel L Costa; Jeffery S Tepper; Darrell W Winsett; Ralph Slade
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Respiratory physiology & neurobiology     Volume:  145     ISSN:  1569-9048     ISO Abbreviation:  Respir Physiol Neurobiol     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-11     Completed Date:  2005-05-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  101140022     Medline TA:  Respir Physiol Neurobiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  183-99     Citation Subset:  IM    
Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research Development, U.S. Environmental Protection Agency, B 143-01 Research Triangle Park, NC 27711, USA.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology
Aerosols / pharmacology
Airway Resistance / drug effects*
Anoxia / metabolism,  physiopathology
Blood Pressure / drug effects
Bronchoconstriction / drug effects
Cardiovascular System / drug effects*
Dose-Response Relationship, Drug
Drug Interactions
Guinea Pigs
Heart Rate / drug effects
Histamine / pharmacology
Methacholine Chloride / pharmacology*
Muscarinic Agonists / pharmacology*
Ovalbumin / pharmacology
Oxygen / metabolism
Partial Pressure
Plethysmography / methods
Propranolol / pharmacology
Pulmonary Gas Exchange / drug effects*
Random Allocation
Reaction Time / drug effects
Respiratory Mechanics / drug effects,  physiology
Respiratory System / drug effects*
Tidal Volume / drug effects
Time Factors
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Aerosols; 0/Muscarinic Agonists; 51-45-6/Histamine; 525-66-6/Propranolol; 62-51-1/Methacholine Chloride; 7782-44-7/Oxygen; 9006-59-1/Ovalbumin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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