CHRONIC PLATELET-ACTIVATING-FACTOR INDUCES A DECREASE IN PULMONARY VASCULAR COMPLIANCE, HYDROXYPROLINE, AND LOSS OF VASCULAR MATRIX

We have previously demonstrated that chronic intravenous platelet-acti vating factor (PAF) induces morphologic remodeling of pulmonary arteri es characterized by a decrease in internat and external elastic lamina circumference, pulmonary arterial contracture, and internal elastic l amina duplication. The mechanism of PAF-induced arterial contracture i s unknown. In this study we determined whether PAF caused arterial con tracture through cell loss by calculating the number of cell nuclei/to tal cross-sectional area of arteries. The nuclear ratio was increased in intra- and preacinar pulmonary arteries of PAF-treated rabbits. Hyd roxyproline content of lungs stratified by anatomic region was signifi cantly reduced in intra-acinar tissue of PAF-treated rabbits, indicati ng that PAF-induced vascular contracture was associated with toss of i nterstitial collagen. We next tested whether these morphologic alterat ions were associated with decreased pulmonary vascular compliance and increased resistance. Compliance and resistance were determined in iso lated, perfused lungs from rabbits chronically treated with PAF. Compl iance was calculated: (1) from the slope of the venous occlusion trace (CVO), (2) by increasing left atrial pressure (CLA), (3) by increasin g flow (CHF), and (4) by the classic static technique (CAV) Of adding volume (2 mi) to a passively drained lung. Vascular compliance was sig nificantly reduced in PAF-treated lungs when measured by all four meth ods; however, pulmonary vascular resistance was unchanged. We conclude that structural changes that result from chronic intravenous PAF infu sion affect the elastic modulus to a greater extent than factors that influence pulmonary vascular resistance.