ADP-induced second wave aggregation in platelet rich plasma from hypercholesterolemic rabbits

Platelet aggregation, ATP secretion and thromboxane formation were measured in platelet-rich plasma (PRP) of rabbits fed a cholesterol-rich (1%) diet for 3 months. Addition of ADP (0.6-2 microM) resulted in a clear biphasic aggregation in 7/8 cholesterol-fed rabbits. This was not seen in any of the 9 control animals kept on a standard diet for the same period of time (P less than 0.01). The secondary ADP-induced aggregation was irreversible and was accompanied by enhanced ATP secretion and significant thromboxane generation. There was no ADP-induced thromboxane formation and only a minor ATP secretion at the highest ADP concentration studied (20 microM) in control rabbits. These data confirm platelet hyperreactivity in hypercholesterolemia and demonstrate for the first time the occurrence of an ADP-induced second wave aggregation and granule secretion in citrated PRP of rabbits which may be triggered by thromboxane generation.