| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, USA
2 Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA
3 Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, USA; Division of Pediatrics Pulmonary Medicine, Children's Memorial Hospital and Northwestern University, Chicago, IL, USA
4 Physiology, Harvard School of Public Health, Boston, MA, USA
5 Neurobiology and Physiology, Northwestern University, Evanston, IL, USA
* To whom correspondence should be addressed. E-mail: jsolway{at}medicine.bsd.uchicago.edu.
There is abundant evidence that tidal breathing, and especially tidal breathing at elevated minute ventilation, antagonizes the development and persistence of airflow obstruction during bronchoconstrictor stimulation in normal animals and people. Here, we studied the anti-obstructive effect of different tidal breathing patterns in C57Bl/6J and A/J mice during bronchoconstriction induced by continuous or bolus infusion of methacholine. Anesthetized, paralyzed mice were mechanically ventilated at 1500 ml.kg-1.min, using each of 3 breathing patterns: 5 ml/kg, 300 br/min; 10 ml/kg, 150 br/min; or 20 ml/kg, 75 br/min. Changing from 10 ml/kg, 150 br/min to 20 ml/kg, 75 br/min breathing functionally antagonized bronchoconstriction, reducing the level of airflow obstruction induced by methacholine infusion or boluses equivalently in both strains. In marked contrast, changing from 10 ml/kg, 150 br/min to 5 ml/kg, 300 br/min breathing substantially exacerbated methacholine-induced airflow obstruction in A/J mice whereas it had no significant effect in C57Bl/6J mice. Our results therefore demonstrate that: 1) even at moderate, fixed minute ventilation, the precise breathing pattern can influence the degree of airflow obstruction substantially, and 2) the influence of breathing pattern on bronchoconstriction differs considerably between genetically diverse inbred mouse strains. These findings imply that differences in anti-obstructive effects of breathing can contribute to differences in apparent airway constrictor responsiveness. Much attention has been placed on dysregulation of contractile function of airway smooth muscle in human disease. We suggest that important pathophysiology might also be found in impairment of the functional antagonist effect of tidal breathing on airflow obstruction.
This article has been cited by other articles:
|
|
 |
|
  M. J. Sanderson, P. Delmotte, Y. Bai, and J. F. Perez-Zogbhi Regulation of Airway Smooth Muscle Cell Contractility by Ca2+ Signaling and Sensitivity Proceedings of the ATS, January 1, 2008; 5(1): 23 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. T. B. Nguyen and J. J. Fredberg Strange Dynamics of a Dynamic Cytoskeleton Proceedings of the ATS, January 1, 2008; 5(1): 58 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Mitchell, M. L. Dowell, J. Solway, and O. J. Lakser Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle Proceedings of the ATS, January 1, 2008; 5(1): 68 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Solway and C. G. Irvin Airway Smooth Muscle as a Target for Asthma Therapy N. Engl. J. Med., March 29, 2007; 356(13): 1367 - 1369. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
