Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque

Abstract

Defined angiographically, no-reflow (NR) manifests as an acute reduction in coronary flow in the absence of epicardial vessel obstruction. One candidate protein to cause coronary NR is tissue factor (TF), which is abundant in atherosclerotic plaque and a cofactor for activated plasma coagulation factor VII. Scrapings from atherosclerotic carotid arteries contained TF activity (corresponding to 33.03 ؎ 13.00 pg/cm 2 luminal plaque surface). Active TF was sedimented, indicating that TF was associated with membranes. Coronary blood was drawn from 6 patients undergoing coronary interventions with the distal protection device PercuSurge GuardWire (Traatek, Miami, FL). Fine particulate material that was recovered from coronary blood showed TF activity (corresponding to 91.1 ؎ 62.16 pg/mL authentic TF). To examine the role of TF in acute coronary NR, blood was drawn via a catheter from coronary vessels in 13 patients during NR and after restoration of flow. Mean TF antigen levels were elevated during NR (194.3 ؎ 142.8 pg/mL) as compared with levels after flow restoration (73.27 ؎ 31.90 pg/mL; P ‫؍‬ .02). To dissect the effects of particulate material and purified TF on flow, selective intracoronary injection of atherosclerotic material or purified relipidated TF was performed in a porcine model. TF induced NR in the model, thus strengthening the concept that TF is causal, not just a bystander to atherosclerotic plaque material. The data suggest that active TF is released from dissected coronary atherosclerotic plaque and is one of the factors causing the NR phenomenon. Thus, blood-borne TF in the coronary circulation is a major determinant of flow. (Blood. 2002;99:2794-2800)

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

“…The small, but not significant, increase of catecholamines probably reflects the stress situation during percutaneous coronary intervention. In patients with acute coronary syndromes, a release of tissue factor into the aspirate has been reported (6). In line with our current and prior results, it appears that the release of tissue factor is attributed to thrombotic processes and not to the underlying atherosclerotic substrate and therefore only seen during acute coronary syndromes, but not during elective interventions.…”

Association of monocyte count on admission with angiographic no-reflow after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction

“…Besides activation of monocyte adhesion onto endothelial cells, MCP-1 induces the expression of tissue factor, superoxide anions, and exerts prothrombotic effects [16,17]. Evidence of studies suggest that these factors may contribute to the development on no-reflow [18][19][20]. The other explanation for the relationship between monocytes and no-reflow may be related to microvascular obstruction.…”

Increased vascular wall thrombogenicity combined with reduced blood flow promotes occlusive thrombus formation in rabbit femoral artery

“…Some animal studies have revealed that the rupture of atherosclerotic lesions induces rapid and obvious increases in distal vascular resistance caused by severe microvascular constriction, 22 and that coronary microembolism induces a transient decrease of coronary blood flow. 23 Bonderman et al 24 have emphasized the importance of circulating TF released from disrupted plaques in this process. A clinical study has found Ϸ80% reduction in coronary blood flow during ischemia in patients with unstable angina.…”