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)

Adaptive remodeling is associated with a higher rate of MACE, target lesion restenosis and nontarget de novo stenosis. This finding may be due to differential responses of the adaptively remodeled vessel to revascularization and a generally accelerated course of systemic atherosclerosis.

Acute coronary syndrome is characterized by compromised blood flow at the epicardial and microvascular levels. We have previously shown that thrombectomy in ST-elevation myocardial infarction (STEMI) accelerates ST-segment resolution, possibly by preventing distal embolization. We hypothesized that thrombus constituents contribute to microcirculatory dysfunction. Therefore, we analyzed the molecular and cellular composition of acute coronary thrombi, and correlated vasoconstrictive mediators with the magnitude of ST-segment resolution within one hour of percutaneous coronary intervention (PCI). Fresh coronary thrombi were retrieved in 35 consecutive STEMI patients who were treated with the X-Sizer thrombectomy catheter, and thrombus cell counts and vasoconstrictor concentrations were assessed. Twelve-lead ECG recordings were analyzed prior to and one hour after PCI. Concentration of endothelin (ET) was 20.0 (7.9-52.2) fmol/ml in thrombus compared with 0.1 (0.1-0.3) fmol/ml in corresponding peripheral plasma (p < 0.0001), representing a selective 280 (70.0-510.0)-fold enrichment, exceeding enrichment of noradrenaline, angiotensin II and serotonin. Human coronary thrombus homogenates exerted vasoconstriction of porcine coronary artery rings that was inhibited by the dual ET receptor blocker tezosentan. Extracted ET (r = 0.523 p = 0.026) and number of leukocytes (r = 0.555 p = 0.017) were correlated with the magnitude of ST-segment resolution. In conclusion, the amount of active ET and white blood cells aspirated from STEMI target vessels correlated with improvement of territorial microcirculatory function as illustrated by enhanced ST-segment resolution.