A parallel plate flow chamber and an epifluorescence video microscopy system were used to investigate the inhibitory effect of a novel antiplatelet agent (GT-12), a carbamoylpiperidine congener, on surface platelet aggregation and on the kinetics of thrombus growth induced by collagen-coated glass under controlled flow. Both macroscopic and microscopic measurements revealed that increasing concentrations of the drug correspondingly decreased the reaction rate between platelets at the surface, thereby reducing thrombus rate of growth at the surface. Because of decreased platelet/platelet adhesion, there was some embolization of the larger thrombi near the inlet of the reactive surface. In the presence of GT-12, average thrombus size and number of platelets per thrombus were both strikingly lowered. In addition, the net rate of growth of individual thrombi decreased to zero after short exposure times (about 60 seconds), in sharp contrast to controls. In contrast to chlorpromazine, GT-12 was effective in inhibiting platelet aggregation and thrombus rate of growth at relatively low concentrations (less than 100 mumol/L) in whole blood. The drug's effectiveness relative to controls in impeding platelet/platelet interactions was found to increase with decreasing incubation time and increasing perfusion time.
SummaryEpi-fluorescent video microscopy was used to evaluate the effect of ethanol on platelet mural thrombus formation. Whole blood, treated with ethanol, was perfused over collagen coated glass in a parallel-plate flow chamber at a shear rate of 1,000/s. Digital image processing and photodiode measurements were used to analyze the dynamics of thrombus growth on this surface. Ethanol concentrations as low as 0.02% v/v were found to inhibit 45 + 33% (± S.D.) of normal platelet accumulation on the slide while 0.2% v/v ethanol effected an 82 ± 15% inhibition of mural thrombus formation. While platelet adhesion to the collagen surface appeared unaffected by ethanol concentrations up to 0.1% v/v, 0.2% v/v ethanol had an effect on adhesion as well as aggregation. These results imply that low ethanol concentrations inhibit the formation of mural thrombi in a model of a damaged blood vessel at physiological shear rates. This inhibition would not be detected in systems which measure bulk aggregation, e.g. in aggregometric determinations.
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