Prevention of spinal cord injury after transient aortic clamping with tissue factor pathway inhibitor.
BACKGROUND
Lower limb paralysis that occurs in 11% of patients after treatment of thoracic and thoracoabdominal aortic aneurysms is unpredictable and at present not preventable. The proposed cause for the neurologic changes is believed to be spinal cord ischemia combined with ischemia/reperfusion injury. Recombinant tissue factor pathway inhibitor (rTFPI), a multivalent Kunitz-type inhibitor that binds to tissue factor-VIIa complex, was evaluated.


METHODS
The effectiveness of rTFPI as an agent to limit spinal cord ischemia/reperfusion injury was studied in a rabbit spinal cord made ischemic for 20 minutes. rTFPI or phosphate-buffered saline solution (control) was given in randomized blinded fashion at the onset and conclusion of ischemia. Animals underwent neurologic evaluation at 24 hours in a blinded fashion with a modified Tarlov Scale to rate the lower limb paralysis (score of 4 = normal function, score of 0 = complete paralysis).


RESULTS
Seventy-five percent of the TFPI-treated animals had Tarlov scores of 3 to 4, whereas only 29% of the animals treated with phosphate-buffered saline solution had such scores (p < 0.0014). Spinal cord histologic findings correlated with the neurologic findings.


CONCLUSIONS
We believe that TFPI has unique inhibitory properties that make it an effective agent in limiting postoperative paraplegia associated with spinal ischemia.
Koudsi
B
B
Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Yu
C D
CD
Ferguson
E W
EW
Miller
G A
GA
Merkel
K D
KD
Wun
T C
TC
Kraemer
B A
BA
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors; D008074:Lipoproteins / Q000627:therapeutic use*; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000473:pathology / Q000517:prevention & control*
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D008074:Lipoproteins; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor