TISSUE FACTOR PATHWAY INHIBITOR PROTECTS THE ISCHEMIC SPINAL-CORD

Tissue factor pathway inhibitor (TFPI) is a novel agent that binds to tissue factor/VIIa complex and factor-X(a), thereby reducing the effec t of tissue factor (TF) on inflammation and the extrinsic pathway of c oagulation. We hypothesize that systemic treatment with TFPI may limit ischemia-reperfusion (IR) injury. Our experiment was designed to eval uate the effects of TFPI on IR in the spinal cord, Twenty-three adult New Zealand white rabbits had snare occlusion devices placed circumfer entially around the aorta and tunneled to a subcutaneous position, For ty-eight hours later, in the fully awake state, the animals were treat ed with either TFPI (1 mg/kg bolus followed by a 1-hr infusion of 20 m u g/kg/min), or heparin (100 U/kg bolus) followed by a 1-hr infusion o f 10 ml/kg/hr of PBS while controls received phosphate buffered saline (20 ml followed by a 1-hr infusion of 10 ml/kg/hr). The infrarenal ao rta was occluded for 21 min in all groups via the snare device, Animal s were observed for 3 days and neurologic recovery was graded by the T arlov criteria. Results were evaluated as percent of animals with hind limb recovery (Tarlov 3 and 4). At 24 hr postocclusion, 88% of the TFP I-tpeated animals had recovered neurologic function versus only 20% of heparin-treated animals and 10% of the phosphate buffered saline grou p (P = 0.031 and 0.009, respectively). At 72 hr, 63% of the TFPI anima ls retained neurologic function versus 20% of heparin-treated animals and 10% of phosphate buffered saline-treated animals (P = 0.032, TFPI versus phosphate buffered saline). The mechanism of action of TFPI is not completely understood, yet this drug may hold promise in the preve ntion of IR injury of the spinal cord. (C) 1996 Academic Press, Inc.