Resolution of venous thrombosis using a novel oral small-molecule inhibitor of P-selectin (PSI-697) without anticoagulation.

P-selectin inhibition has been shown to decrease thrombogenesis in multiple animal species. In this study, we show that a novel oral small-molecule inhibitor of P-selectin, PSI-697, promotes thrombus resolution and decreases inflammation in a baboon model of venous thrombosis. Experimental groups consisted of the following: 1) primates receiving a single oral dose of PSI-697 (30 mg/kg) daily starting three days pre-iliac vein balloon occlusion, and continued for six days; 2) primates receiving a single treatment dose of a low-molecular-weight-heparin (LMWH) (1.5 mg/kg) daily starting one day pre-iliac balloon occlusion, and continued for six days; and 3) primates receiving a single oral dose of a vehicle control daily starting three days pre-iliac vein balloon occlusion, and continued for six days. Animals receiving PSI-697, although thrombosed after balloon deflation, demonstrated greater than 80% vein lumen opening over time, with no opening (0%) for vehicle control (p < 0.01). LMWH opening evident after balloon deflation slightly deteriorated over time compared to PSI-697. PSI-697 therapy also significantly decreased vein wall inflammation determined by magnetic resonance venography (MRV). Importantly, this beneficial opening occurred without measured anticoagulation. Animals receiving PSI-697 demonstrated significantly increased plasma D-dimer levels versus LMWH and control animals six hours post thrombus induction (p < 0.01). This study is the first to demonstrate the effectiveness of oral P-selectin inhibition to modify venous thrombogenesis, increase vein lumen opening, and decrease inflammation in a large animal model.

Delineation of lateral tentorial sinus with contrast-enhanced MR imaging and its surgical implications.

BACKGROUND AND PURPOSE: The lateral tentorial sinus (LTS) has not been well described in the imaging literature. The aim of this study was to investigate the value of MR imaging in assessing the LTS, which may provide guidance for preoperative planning. METHODS: Fifty-five adult patients underwent MR imaging of the brain. Four neuroradiologists evaluated the studies for delineation of the LTS and its branches. Presence of arachnoid granulation and dominance of the venous drainage also were reported. RESULTS: An LTS was detected in 104 of 110 lobes. The LTS in each lobe was classified as type I (candelabra) in 30 (28.8%), type II (independent veins) in 22 (21.1%), and type III (venous lakes) in 37 (35.5%); in 15 (14.4%) of the lobes, the LTS was indeterminate. LTS branches were inconsistently detected, with the exception of the vein of Labbé (VL). Five of eight branches were seen in approximately half of the cases. The VL was identified in 94 (85.4%) lobes. Among these, 53 (56.4%) were draining into the LTS and 22 (23.4%) into the transverse sinus; in 19 (20.2%) cases, the terminal portion was not visualized. The right transverse sinus was dominant in 19 (34.5%) patients and the left in 18 (32.7%); codomination was present in 18 (32.7%) cases. At least one arachnoid granulation was seen in the transverse sinus in 27 (49.1%) patients. CONCLUSION: In many instances, the LTS and VL drainage patterns were well delineated on routine MR images. For selected cases, this information may be crucial during lateral skull base surgery to avoid venous infarct.