Platelet aggregation in flowing blood in vitro. II. Dependence of aggregate growth rate on ADP concentration and shear rate

Abstract

Experiments were carried out with citrated dog blood using the new experimental system described in the companion paper (E. F. Grabowski, 1978, Microvas. Res. 16, 159–182). In this system, platelet aggregates form at and adhere to a specified, microscopic site on Cuprophan (PT 150, Enka Glanzstoff) membrane. Important features include controlled surface shear rate, controlled ADP diffusion through the membrane and into the flowing blood at the microscopic site, and quantification of aggregate growth rates by videodensitometry. In early trials it was learned that prior platelet adhesion markedly enhanced aggregation in response to ADP; the degree of prior adhesion was therefore standardized for subsequent experiments. When rate of entry of ADP was increased logarithmically, the rate of change of mean thickness of platelet aggregates adherent to the membrane increased monotonically. With an entry rate leading to ADP in micromolal concentrations at the membrane-blood interface, however, growth rate prior to embolization passed through a maximum with respect to surface shear rate (varied from 99 to 986 sec −1). The maximum occurred between 394 and 635 sec −1, the growth rate at 394 sec −1 being, for example, 3.1 ± μm/min (mean ± SD for three animals). On the other hand, aggregate growth rate for an entry rate leading to millimolal ADP increased monotonically with increasing shear rate over the same range. Aggregate growth rates appear therefore to be limited at low shear rate by platelet convection, but at higher shear rates by one or more of (1) dilution of ADP, (2) finite platelet-ADP interaction times, and (3) surface shear stress. For the range of shear rates studied, dilution of ADP seems likely to be the most important of these last factors.