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Published ahead of print on July 17, 2003, doi:10.1164/rccm.200207-690OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 9, November 2003, 1068-1074

A more recent version of this article appeared on November 1, 2003
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Submitted on July 15, 2002
Accepted on July 8, 2003

AIRWAY DISTENSION PROMOTES LEUKOCYTE RECRUITMENT IN RAT TRACHEAL CIRCULATION

Lina H.K. Lim1 and Elizabeth M Wagner1*

1 Medicine, Johns Hopkins University, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: wagnerem{at}jhmi.edu.

Mechanical distortion of blood vessels is known to activate endothelial cells. Whether airway distension likewise activates the vascular endothelium within the airway wall is unknown. Using intravital microscopy in the rat trachea, we investigated if airway distention with the application of positive end-expiratory pressure (PEEP) caused leukocyte recruitment to the airway. Tracheal post-capillary venules were visualized and leukocyte kinetics monitored in anesthetized, mechanically ventilated rats (80 breaths/min, 6 ml/kg tidal volume, 1 cmH2O PEEP). Leukocyte rolling velocity (Vwbc) and the number of adherent cells were not altered with normal ventilation over the course of 2hrs. Ventilation with sustained PEEP (8 cmH2O) for 1 hour reduced Vwbc and increased adhesion, reaching a maximum at 1 hour of PEEP. Intermittent (x 2 and x 5) 8 cmH2O PEEP also induced a similar reduction in Vwbc, accompanied by an increase in adhesion. However, leukocyte recruitment following airway distension is localized to the airways, since increased PEEP did not induce leukocyte recruitment in the mesenteric microcirculation or when PEEP was applied to the lung distal to the site of measurement. Pretreatment with endothelin receptor and selectin inhibitors blocked the effects of distension on leukocyte recruitment suggesting their involvement in the pro-inflammatory response.
Key words: airway distension; endothelial activation, intravital microscopy; mechanical stress, PEEP




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