The initiation of platelet thrombi in normal venules and its acceleration by histamine

1. In cheek pouch preparations of anaesthetized hamsters, platelet thrombi or ;white bodies' were produced in venules by the micro-ionto-phoretic application of adenosine diphosphate (ADP). Currents of 10-400nA were passed through micropipettes containing 10 mM-ADP, the tips of which were less than 5 mu from the outer wall of the venule. The effect was quantitated by determining the time between starting the currents and the first appearance of platelets adhering inside the venule opposite the tip of the micropipette.2. Repeated applications of ADP to the same site on a venule caused the appearance of white bodies after intervals which were almost constant for up to 3 hr.3. The time to first appearance of a white body was inversely related to the iontophoretic current between about 10 and 200 nA. Currents smaller than 10 nA had no effect on the platelets. With currents of 200 nA or more the time remained at a minimum of less than 20 sec.4. With currents of about 300 nA the minimum time increased little as the pipette tip was withdrawn up to 20 mu from the venule; with greater distances the time increased progressively.5. Histamine caused gaps to appear between endothelial cells in cheek pouch venules. Histamine at a concentration of 10 mM in micropipettes was applied iontophoretically by currents of 300 nA to venules at the same sites as ADP. Histamine alone had no effect on circulating platelets. When applied before and together with ADP, histamine decreased the time to first appearance of white bodies by up to 40% below that determined with ADP alone. Iontophoretically applied histamine did not alter the mean blood flow velocity in the venules.6. After stopping the application of histamine, the time to first appearance of white bodies produced by ADP increased again in about 5 min to the control values.7. Bradykinin, which does not cause endothelial gaps in cheek pouch venules, did not accelerate the induction of white bodies like histamine.8. There were no microscopic abnormalities in venules in which white bodies had formed. Venules exposed to histamine accumulated circulating carbon particles in discrete wall areas.9. It is concluded that adhering white bodies can be induced repeatedly in normal venules by direct action of externally applied ADP on circulating platelets and that the accelerating effect of histamine on white body formation is due to the separation of endothelial cells which accelerates the inward diffusion of ADP.