Inhibitory effects of activated protein C and heparin on thrombotic arterial occlusion in rat mesenteric arteries.

Effects of human activated protein C (APC) and heparin on thrombus formation were examined using small mesenteric arteries of rats and video-recording system attached to a microscope. To induce thrombosis we damaged the vessel wall over a short segment by compression and exposed the damaged media to the blood stream. Platelet-rich thrombus enlarged gradually at the damaged site, occluded the vascular lumen for a short period and then flowed away. Such thrombus formation was observed several times after a compression damage. An intravenous administration of APC significantly decreased the total occlusion time from 6.4 +/- 0.7 min at control to 2.2 +/- 0.4 min at 0.9 mg/kg given over 1 min (mean +/- SEM, n = 6, p less than 0.01), and from 6.5 +/- 1.0 min to 1.0 +/- 0.3 min at 3.0 mg/kg (n = 6, p less than 0.01). An intravenous heparin (300 and 1000 U/kg) also decreased the total occlusion time significantly from 6.2 +/- 0.8 to 2.2 +/- 0.8 min (n = 6, p less than 0.05) and from 5.4 +/- 0.8 to 0.8 +/- 0.7 min (n = 6, p less than 0.01), respectively. APC prolonged APTT from 11 +/- 1 sec (n = 5) at control to 50 +/- 5 sec (n = 5) at 0.9 mg/kg and to 87 +/- 8 sec (n = 5) at 3.0 mg/kg, while heparin prolonged APTT to more than 120 sec in all 5 rats at both doses. APTT prolongation by APC was significantly attenuated by inhibiting its residual activity in the plasma samples using monoclonal antibody.(ABSTRACT TRUNCATED AT 250 WORDS)