Procoagulant activity on injured arteries and associated thrombi is mediated primarily by the complex of tissue factor and factor VIIa.

BACKGROUND: Rethrombosis limits the efficacy of coronary thrombolysis and may result from surface-associated thrombin, de-novo prothrombin activation, or both. This study was designed to determine the relative roles of thrombin, factor Xa, and the complex of tissue factor and factor VIIa in the procoagulant activity on injured arteries with evolving thrombi. METHODS: Extensive vascular injury and platelet-rich thrombi were induced in the abdominal aorta of 25 anesthetized rabbits by applying anodal current through a transluminal electrode for 3 h. Injured vessel segments were excised and placed in a chamber permitting perfusion over the luminal surface and associated thrombus. RESULTS: Vessel segments perfused with recalcified, citrated human plasma induced marked increases in the concentration of fibrinopeptide A, a marker of thrombin-induced fibrin formation, in the effluent plasma after 10 min (4636 +/- 1894% of fibrinopeptide A in the nonperfused plasma, n = 5). Perfusion with plasma depleted of vitamin K-dependent coagulation factors prevented the increase in fibrinopeptide A (122 +/- 30%, n = 4), indicating the lack of preformed functional thrombin. Furthermore, appearance of fibrinopeptide A was attenuated by perfusion with plasma containing 0.1 mumol/l recombinant tick anticoagulant peptide, a specific inhibitor of factor Xa (594 +/- 320%, n = 3), and by preincubation of vessel segments with a monoclonal antibody to rabbit tissue factor (438 +/- 220%, n = 3). CONCLUSIONS: Procoagulant activity on injured vessels and associated thrombi is mediated by factor Xa, a product of the functional initiation of coagulation by factor VIIa associated with tissue factor. Accordingly, inhibition of tissue factor-mediated coagulation may be effective for attenuation of active thrombogenesis on injured vessels and during thrombolysis.

Validation of magnetic resonance imaging (MRI) multispectral tissue classification.

The application of NASA multispectral image processing technology for analysis of Magnetic Resonance Imaging (MRI) scans has been studied. Software and hardware capability has been developed, and a statistical evaluation of multispectral analysis application to MRI scans of the head has been performed.

Tissue factor mediates prolonged procoagulant activity on the luminal surface of balloon-injured aortas in rabbits.

BACKGROUND: Activation of coagulation has been implicated in both acute thrombotic occlusion and restenosis after balloon angioplasty. However, concomitant administration of antithrombotic agents has thus far failed to prevent these complications. Importantly, the factors contributing to procoagulant activity of balloon-injured arteries over time have not been defined. This study was designed to determine the duration of procoagulant activity on the luminal surface of balloon-injured arteries and the relative roles of tissue factor and thrombin in this response. METHODS AND RESULTS: Abdominal aortas in rabbits were subjected to repetitive balloon hyperinflations sufficient to disrupt the internal elastic lamina. Aortas were excised at < 1, 2, 4, 8, 16, 24, 48, and 72 hours and 1, 2, and 4 weeks after injury; divided into segments; and perfused with recalcified human pooled plasma (n = 58) or plasma depleted of vitamin K-dependent coagulation factors (n = 27) or first incubated with a monoclonal antibody to rabbit tissue factor (n = 33) followed by perfusion with human plasma. Samples of the effluent and plasma perfusate were collected over 10 minutes and assayed for fibrinopeptide A (FPA) as an index of the rate of thrombin-induced fibrin formation. FPA in the effluent from segments perfused with recalcified plasma, expressed as a percentage of FPA in the perfusate, was elevated for 16 hours after balloon-induced injury and exhibited two distinct increases occurring < 1 hour (1297 +/- 473%, mean +/- SD, n = 5) and 8 hours (1052 +/- 330%, n = 6) after injury (P < or = .000001 versus uninjured vessels). Preincubation of segments at these intervals with an antibody to tissue factor markedly attenuated the increases in FPA, as did perfusion of segments with plasma depleted of vitamin K-dependent coagulation factors, indicating that the observed increases in FPA in whole plasma did not result from performed thrombin bound to the injured vessel wall. CONCLUSIONS: Tissue factor-mediated coagulation appears to be primarily responsible for prolonged procoagulant activity of balloon-injured arteries.

Coronary artery mapping: a method for three-dimensional reconstruction of epicardial anatomy.

Evaluation of coronary anatomy with conventional coronary angiography requires visual integration of multiple images from different viewing orientations to generate a mental interpretation of three-dimensional (3D) structure. The epicardial surface is, in many ways, analogous to the earth's surface topography and may be effectively depicted using cartographic methods. To show coronary anatomy visualized as topographic maps, we used cartographic projection methods to analyze the coronary vessels of a canine heart after immediate postmortem injection with a radio-opaque gelatinous solution. A volumetric image data set was obtained with x-ray spiral computed tomography. The principal axis of the image volume was calculated and the image volume reformatted to a reference coordinate system defined by the principal axis as the ordinate. A cylindrical projection map of the epicardial surface was created using a maximum-intensity projection volume-rendering technique. After converting the Cartesian reference coordinate system to a polar coordinate system, additional mapping projections from user-defined orientations were generated. The results show that interpretative difficulties of coronary angiography may be diminished by generating 3D maps of coronary anatomy using volumetric datasets acquired noninvasively and displayed with cartographic methods.

Inhibition of tissue factor-mediated coagulation markedly attenuates stenosis after balloon-induced arterial injury in minipigs.

BACKGROUND: Exposure and upregulation of tissue factor in the wall of balloon-injured arteries may result in prolonged activation of coagulation contributing to restenosis. This study was designed to determine whether brief or more prolonged inhibition of tissue factor-mediated coagulation with tissue factor pathway inhibitor (TFPI) attenuates neointimal formation and luminal stenosis after balloon-induced arterial injury. METHODS AND RESULTS: The carotid artery of minipigs fed an atherogenic diet was injured by repetitive balloon hyperinflations, a procedure that rapidly yields complex, plaque-like neointimal lesions and high-grade luminal stenosis. Recombinant TFPI (rTFPI) was administered intravenously beginning 15 minutes before balloon injury as either a high dose (0.5 mg/kg bolus and 100 microg x kg(-1) x min(-1)) for 3 hours (n=7) or 24 hours (n=6) or as a low dose (0.5 mg/kg and 25 microg x kg(-1) x min(-1)) for 24 hours (n=6). Control animals received intravenous heparin (100 U x kg(-1) x h(-1)) for 3 hours (n=6) or 24 hours (n=7) or aspirin (5 mg/kg P.O.) followed by heparin for 24 hours (n=7). Luminal stenosis, assessed histologically 4 weeks after injury, was 73+/-17% and 76+/-18% (mean+/-SEM) in animals that received rTFPI or heparin for 3 hours, respectively. In contrast, luminal stenosis was only 11+/-12% and 6+/-3% in pigs given high and low doses, respectively, of rTFPI for 24 hours compared with 46+/-22% in pigs given heparin for 24 hours and 40+/-19% in those given both heparin and aspirin (P<.0002). CONCLUSIONS: Inhibition of tissue factor-mediated coagulation during the first 24 hours after deep arterial injury appears to be particularly effective for attenuating subsequent neointimal formation and stenosis.