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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.


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
F. Grimminger, K. Mayer, L. Kiss, D. Walmrath, and W. Seeger
PAF-induced synthesis of tetraenoic and pentaenoic leukotrienes in the isolated rabbit lung
Am J Physiol Lung Cell Mol Physiol, February 1, 2000; 278(2): L268 - L275.
[Abstract] [Full Text] [PDF]




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Copyright © 1994 American Thoracic Society