PLATELET-ADHESION AGGREGATION IN AN INVITRO MODEL OF CORONARY-ARTERY STENOSIS

Platelet adhesion/aggregation (PAA)at a site of coronary artery stenosis is believed to be a Process strongly modulated by local shear rates and the functional state of neighboring endothelium. One purpose of the present work, therefore, is to describe an in vitro model for the direct imaging of such PAA. Another is to apply the model to the question as to whether the use of nonionic vs. ionic contrast media (CM) in the presence of vascular endothelium contributes to PAA at the stenosis site. Toward these ends, we utilized a special flow chamber which incorporates a monolayer of endothelial cells (ECs), a step 66% flowpath constriction at a site preadsorbed with microfibrillar collagen, and arterial shear rates. By epifluorescence microscopy and digital image analysis of video recordings, PAA was found to be greater with dysfunctional ECs (pretreated with lysine acetylsalicylate) than with normal ECs, thereby confirming a modulatory role in PAA of functionally intact ECs. When nonionic (iohexol) or ionic (ioxaglate, diatrizoate) CM was added to the flowing blood at a concentration of 20% by non-red cell volume, PAA was inhibited in the order diatrizoate ioxaglate > iohexol > saline control. No inhibition by any CM was seen, however, when chamber prefill culture medium containing 20% by volume CM was displaced by CM-free blood, in simulation of bolus administration of CM. In terms of inhibition of PAA during percutaneous transluminal coronary angioplasty (PTCA), therefore, our model provides a conceptual basis by which one may anticipate in flowing blood no clear benefit of ionic over nonionic CM. This is because the greater antiplatelet effects of the ionic CM are lost with hemodilution by CM-free blood, while a greater anti-EC effect is likely to persist.