Brain-specific protein C activation during carotid artery occlusion in humans

Background and Purpose-Activation of plasma protein C (PC) zymogen by throm bin-thrombomodulin at the endothelial surface is an important endogenous an tithrombotic mechanism. It is unknown whether activated protein C (APC) is generated in vivo in the cerebrovasculature, because there is only Limited thrombomodulin expression in human brain vascular endothelium. Therefore, w e tested the hypothesis that carotid occlusion produces brain-specific PC a ctivation. Methods-Blood samples were simultaneously collected from the ipsilateral in ternal jugular vein and radial artery before and during carotid cross-clamp ing and on "de-occlusion" in 8 awake patients undergoing routine carotid en darterectomy. Plasma PC zymogen and circulating APC levels were measured us ing enzyme immunocapture assay and expressed as percent of pooled plasma co ntrols. Results-Internal jugular vein APC levels increased 28% exclusively during c arotid occlusion and then decreased 32% with de-occlusion (F=8.1, P<0.005). PC zymogen increased only 5.9% with occlusion (F=6.3, P<0.02), consistent with hemoconcentration. There were no changes in radial artery PC or APC le vels. Conclusions-These findings demonstrate brain-specific protein C activation in humans during carotid occlusion and suggest a protective role for endoge nous APC generation during cerebrovascular occlusion.