Possible role of damaged neoendothelial cells in the genesis of coronary stent thrombus in chronic phase. A dye staining angioscopic study.

The mechanism(s) underlying formation of coronary stent thrombus (ST) in chronic phase is yet unclear. Endothelial cells are highly antithrombotic, therefore, it is conceivable that neoendothelial cells (NECs) covering stent struts are damaged and cause ST. This study was performed to examine the role of damaged NECs covering coronary stent struts in the genesis of occlusive or nonocclusive ST in chronic phase.(1) Forty-four patients with acute coronary syndrome (17 females and 27 males) underwent dye-staining coronary angioscopy, using Evans blue which selectively stains damaged endothelial cells, 6 months after bare-metal stent (BMS) deployment. Neointimal coverage was classified into not covered (grade 0), covered by a thin layer (grade 1), and buried under neointima (grade 2) groups. (2) In 7 beagles, the relationships between neointimal thickness and ST were examined 6 months after BMS deployment. (3) The NECs on the struts were stained blue in 4 of 25 patients with grade 2 and in 11 of 20 patients with grade 0/1 (P < 0.05). ST was observed in none of the former and in 5 of the latter (P < 0.05). (4) In beagles, neointimal coverage was grade 0/1 when neointimal thickness was 80.2 ± 40.0 µm, whereas grade 2 when thickness was 184 ± 59.4 µm. ST was observed in 9 of 15 struts with neointimal thickness within 100 µm and in one of 17 struts with thickness over 100 µm (P < 0.05). ST arose from damaged NECs covering the stent struts. NECs may have been damaged due to friction between them and struts due to thin interposed neointima which might have acted as a cushion, resulting in ST.

Fluffy luminal surface of the non-stenotic culprit coronary artery in patients with acute coronary syndrome: an angioscopic study.

BACKGROUND: Approximately 15% of acute coronary syndrome (ACS) cases have no significant coronary stenosis. Mechanisms underlying the attacks are, however, unknown. METHODS AND RESULTS: The clinical study had 254 patients with ACS; 38 patients (31 females and 7 males; aged 51.0 ± 8.0 years) had no significant coronary stenosis on angiography. They underwent a dye-staining angioscopy of the suspected culprit coronary artery using Evans blue, which selectively stains fibrin and damaged endothelial cells. A fluffy coronary luminal surface was observed in the suspected culprit artery in all 38 patients. The fluffy luminal surface was stained blue with Evans blue. In animal experiments involving 5 beagles, 10% hydrogen peroxide solution was injected into the iliac arteries to damage endothelial cells, which was then followed by blood reperfusion, and then the artery was examined by intravascular microscopy and histology. In the beagles, the arterial segment, where the thrombus had been formed, exhibited a fluffy luminal surface after a washout of the thrombus, and the surface was stained blue. Histologically, the fluffy surfaces were composed of damaged endothelial cells attached by multiple fibrin threads and platelets. CONCLUSIONS: It was considered that the coronary segment exhibiting a fluffy luminal surface was the culprit lesion and that the fluffy surface was caused by residual thrombi after dispersion of an occlusive thrombus, which had formed on the damaged endothelial cells.

Role of a streamer-like coronary thrombus in the genesis of unstable angina.

INTRODUCTION: It is generally believed that the coronary occlusion occurs at the site of plaque disruption in acute coronary syndromes. An exceptional mechanism of coronary occlusion, namely a streamer-like thrombus (SLT) originating in a nonstenotic lesion extended distally to obstruct a just distal nondisrupted stenotic segment, was found by angioscopy in patients with unstable angina (UA). This study was carried out to examine the incidence of this phenomenon and its relationship to the subtypes of UA. METHODS: The culprit coronary artery was investigated by angioscopy in successive 48 patients (mean +/- SE age, 61.0 +/- 2.3 years; 10 females and 38 males) with UA. RESULTS: SLT originating in a nonstenotic lesion extended distally, and obstructed the just distal most stenotic segment (DMSS) by its tail in 11 patients (eight with class III and three with class II according to Braunwald's classification). Recurrent anginal attacks were observed in all. The nonstenotic lesion in which the SLT originated was a disrupted yellow plaque in most cases. The SLT was frequently red and yellow in a mosaic pattern, indicating a mixture of fresh thrombus and plaque debris. The plaques that constructed the DMSS were not disrupted. Angiographically, the SLT was not detectable and the entry of the DMSS showed a "tapering" configuration. CONCLUSIONS: Obstruction of the DMSS by the tail of SLT originating in a nonstenotic lesion is another mechanism of UA. Therefore, treatment of both the nonstenotic lesion and DMSS is needed to prevent recurrent thrombus formation and consequent reattacks.

Possible participation of endothelial cell apoptosis of coronary microvessels in the genesis of Takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TCM) is characterized by systolic ballooning of the left ventricular apex. It is triggered by emotional or physical stress, but the exact mechanism through which stress leads to TCM is not known. HYPOTHESIS: Coronary microvessel apoptosis is the missing link between stress and TCM. METHODS: In 8 female patients with TCM, plasma catecholamines, Thrombolysis in Myocardial Infarction (TIMI) coronary flow grade and myocardial perfusion grade, and apoptosis of the coronary microvessels in the biopsied myocardial specimen by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) were examined. RESULTS: Plasma epinephrine and norepinephrine were increased to 663 +/- 445 and 875 +/- 812 pg/mL (mean +/- SD), respectively. Acetylcholine-induced delayed myocardial perfusion through the ballooning apical segment without flow disturbance in the epicardial coronary arteries (indicating microvessel spasm) and focal myocardial necrosis were observed in all subjects. Apical ballooning disappeared and myocardial perfusion delay was not inducible 1 month later. The number of vessels having apoptotic endothelial cells/10 vessels in arterioles, venules, and capillaries at initial biopsy and repeat biopsy 1 month later were 8.3 +/- 1.4 vs 0.4 +/- 1.1, P < 0.0001; 6.8 +/- 1.8 vs 0.3 +/- 0.7, P < 0.0001; and 7.9 +/- 1.0 vs 0.5 +/- 0.9, P < 0.0001, respectively. CONCLUSIONS: Left ventricular apical ballooning in TCM was considered to be caused by coronary microvessel spasm due to catecholamine-induced endothelial cell apoptosis and myocardial stunning after release of microvessel spasm. Endothelial cell apoptosis of coronary microvessel is therefore considered to be the missing link between stress and TCM.

Angioscopic detection of pulmonary thromboemboli: with special reference to comparison with angiography, intravascular ultrasonography, and computed tomography angiography.

INTRODUCTION: Pulmonary embolism (PE) is often fatal and its incidence is increasing worldwide. Detection of thromboemboli (TEi) is essential for a definitive diagnosis of PE. The detection of TEi using most imaging methods is low in patients clinically suspected of having PE. This study was carried out to detect TEi in the pulmonary arterial trees by angioscopy (AS); to classify TEi; and to compare the sensitivity of detection for TEi among AS, angiography (AG), intravascular ultrasonography (IVUS), and computed tomography angiography (CTA) in patients with clinically suspected PE. METHODS: After CTA, AG, and IVUS, the pulmonary arterial trees were surveyed by AS in 49 patients clinically suspected of having PE. RESULTS: TEi were found by AS, AG, IVUS, and CTA in 81.6%, 24.4%, 34.8%, and 22.5% of 49 patients, respectively. The 48 TEi classified by AS were globular (35%), mural (10%), cap-like (8%), web-like (4%), patchy (33%), and micro (18%). Cap-like, patchy, and micro-TEi were not detectable by AG, IVUS, and CTA in any subjects. TEi color was classified as red, white, yellow, and red-and-yellow in a mosaic pattern in 10%, 31%, 38%, and 18%, respectively. Red and white globular TEi were observed in acute, and red-and-yellow TEi in both acute and chronic PE patients. TEi other than globular were observed in both patient groups. CONCLUSION: Although invasive, AS is superior to AG, IVUS, and CTA for the detection of TEi, and therefore is a helpful imaging method for the definitive diagnosis of PE.