© 1995 American Heart Association, Inc.
Articles |
Pulmonary Microvascular Permeability
Responses to High Vascular Pressure After Induction of Pacing-Induced Heart Failure in Dogs
From the Department of Physiology, University of South Alabama, Mobile, and the Department of Medicine, University of California at San Diego, La Jolla.
Correspondence to Mary I. Townsley, PhD, Department of Physiology, MSB 3024, University of South Alabama, Mobile, AL 36688.
Abstract The pressure threshold for injury of
pulmonary capillaries is 
50 to 55 cm H2O in the
canine lung, as measured by changes in the filtration coefficient
(Kf,c). Since the pulmonary
endothelial basement membrane has been observed to
thicken in patients with heart failure and pulmonary venous
hypertension, we hypothesized that both baseline permeability and the
threshold for high-vascular-pressure injury would be altered as a
result. Dogs (n=12) were chronically paced at 245 beats per minute for
4 weeks, then were paced at 225 beats per minute for an additional 3
weeks. Lung lobes from anesthetized paced dogs and additional
control dogs (n=14) were then isolated, ventilated, and perfused with
blood. Although vascular resistance was increased nearly threefold and
vascular compliance reduced by 50% in the paced group,
Kf,c referenced to 1 g blood-free dry weight was
no different from control. Despite this lack of difference at normal
pulmonary vascular pressures, several significant results were
obtained. First, in the paced group there was a significant increase in
the threshold for high-vascular-pressure injury:
Kf,c measured at pulmonary vascular
pressures commonly seen in heart failure (20 to 50 cm H2O)
were significantly less in this group compared with control. Model
predictions showed that in vivo, this difference in
Kf,c would result in a 50% reduction in the
amount of water and protein cleared across the pulmonary
capillary endothelial barrier in the paced group. Next,
challenge with high vascular pressure resulted in less accumulation of
residual blood in this group compared with control. Finally, in
separate groups of animals, morphometric analysis of the
alveolocapillary barrier showed that after either 4 or 7 to 8 weeks of
pacing, endothelial, interstitial, and
epithelial thicknesses were increased compared with control. Together,
these results suggest that vascular remodeling confers a modest but
important increase in the resistance of these lungs to
high-vascular-pressure injury and the development of alveolar edema.
Key Words: pulmonary circulation • isolated lung • capillary filtration coefficient • osmotic reflection coefficient • stretched pore phenomenon
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