Differential effects of salmeterol on lung endothelial and
epithelial leakage in sheep.
Peterson, Barry T., David E. Griffith, Jon C. Connelly, and Randy W.
Tate.
Departments of Physiology and Medicine, The University of Texas
Health Center at Tyler, P.O. Box 2003, Tyler, TX 75710
APStracts 3:0017A, 1996.
Salmeterol has been shown to prevent the influx of proteins into the
air spaces of lungs of guinea pigs given intravenous histamine. To
determine whether the salmeterol acts to stabilize the epithelial or
endothelial barrier, we ventilated anesthetized sheep with
aerosolized salmeterol before infusing histamine intravenously at a
rate of 4 [mu]g/kg/min for 3 hours. Changes in endothelial
permeability were assessed by measuring the flow of lymph and
proteins from the lungs. The influx of proteins into the air spaces
was detected by performing single-cycle lavages to measure the
concentration of circulating 125I-albumin in the epithelial lining
fluid (ELF). Intravenous histamine increased the lymph flow to 13.2
+/- 6.8 ml/hr compared to the control value of 5.6 +/- 2.8 ml/hr
(p<0.05). Histamine also increased the concentration of 125I
-albumin in the ELF from 1.8 +/- 0.9 to 8.5 +/- 2.5 % of the plasma
concentration (P<0.01) and the postmortem lung water volume from
3.5 +/- 0.5 to 5.0 +/- 0.8 mg/gm dry lung weight (p<0.05).
Pretreatment with 2.5 mg of aerosolized salmeterol prevented the
influx of proteins into the airspaces and the increase in the
postmortem lung water volume, but it also increased the lung lymph
flow even further to 20.0 +/- 5.6 ml/hr (p<0.05), increased the
lymph to plasma protein ratio from 0.77 to 0.91, and tripled the
increase in alveolar-arterial oxygen gradient caused by histamine
alone. Pretreatment with 2.5 mg of intravenous salmeterol had
essentially the same effect as salmeterol administered by aerosol. We
conclude that salmeterol decreases lung epithelial permeability but
increases lung endothelial permeability due to intravenous histamine
in sheep.
Received 5 June 1995; accepted in final form 26 December 1995.
APS Manuscript Number A590-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96