Am. J. Respir. Crit. Care Med., Vol 149, No. 6, Jun 1994, 1628-1634.
Chronic platelet-activating factor induces a decrease in pulmonary vascular compliance, hydroxyproline, and loss of vascular matrix
JA Ohar, KS Waller, J Pantano, DE Demello and TE Dahms
Department of Internal Medicine, St. Louis University Medical Center, MO 63110-0250.
We have previously demonstrated that chronic intravenous platelet-
activating factor (PAF) induces morphologic remodeling of pulmonary
arteries characterized by a decrease in internal and external elastic
lamina circumference, pulmonary arterial contracture, and internal elastic
lamina duplication. The mechanism of PAF-induced arterial contracture is
unknown. In this study we determined whether PAF caused arterial
contracture through cell loss by calculating the number of cell
nuclei/total cross-sectional area of arteries. The nuclear ratio was
increased in intra- and preacinar pulmonary arteries of PAF-treated
rabbits. Hydroxyproline content of lungs stratified by anatomic region was
significantly reduced in intra-acinar tissue of PAF-treated rabbits,
indicating that PAF-induced vascular contracture was associated with loss
of interstitial collagen. We next tested whether these morphologic
alterations were associated with decreased pulmonary vascular compliance
and increased resistance. Compliance and resistance were determined in
isolated, perfused lungs from rabbits chronically treated with PAF.
Compliance was calculated: (1) from the slope of the venous occlusion trace
(CVO), (2) by increasing left atrial pressure (CLA), (3) by increasing flow
(CHF), and (4) by the classic static technique (CAV) of adding volume (2
ml) to a passively drained lung. Vascular compliance was significantly
reduced in PAF-treated lungs when measured by all four methods; however,
pulmonary vascular resistance was unchanged. We conclude that structural
changes that result from chronic intravenous PAF infusion affect the
elastic modulus to a greater extent than factors that influence pulmonary
vascular resistance.