After coronary angiography, an angioscope was introduced into the targeted coronary artery. The balloon of the angioscope was inflated to stop the blood flow therein. The fiberscope incorporated into the angioscope was slowly advanced up to 7 cm distally to facilitate successive observations of the artery while displacing the blood by infusion of heparinized saline solution (10 IU/mL) at a rate of 2 mL/s for 10–20 s through the flush channel of the angioscope. To accurately confirm the location of the angioscope tip (and accordingly the observed portion), the angioscopic and fluoroscopic images were displayed simultaneously on a television monitor.

After observation by conventional AS, one mL of 2.5 % Evans blue (EB) solution was injected during balloon inflation into the artery through the flush channel of the angioscope to stain the damaged endothelial cells or fibrin, and then the balloon was deflated for blood flow restoration. One to 2 min later, the balloon was inflated again and the coronary luminal surface was observed by AS.

Coronary endothelial cells protect the vascular wall against spasm and thrombus formation through release of vasodilating and antithrombotic substances. When the endothelial cells are damaged, thrombus is immediately formed on them. However, it has been difficult to visualize the damaged endothelial cells in patients in vivo.

The present authors succeeded in visualizing the damaged coronary endothelial cells. Namely, it became clear that coronary endothelial damages are caused by insertion of a catheter for percutaneous intervention, balloon inflation, and even by insertion of a guidewire (Fig. 3.2) [3, 5].

Platelet thrombi play the key role in the genesis of ACS and it was generally considered that the white thrombus is platelet thrombus [9].

We performed dye-staining coronary AS study using EB as a marker of fibrin to examine whether white coronary thrombi in patients with ACS are composed of platelets alone. It became clear that the majority of white thrombi (so-called platelet thrombi) were clearly discriminated into fibrin-rich and platelet-rich thrombi (Fig. 3.3) [3].

This imaging modality may contribute to the selection of effective primary or adjunctive thrombolytic therapy.

Figure 3.4 shows a patient with unstable angina (UA) in whom the left anterior descending artery was totally occluded by angiography. However, a residual lumen was observed and nothing was seen in the lumen by conventional AS. Dye-staining AS exposed a blue structure occupying the residual lumen, indicating that it was a fibrin thrombus that caused total occlusion. Transparent fibrin thrombi, namely, a structure that was not visible by conventional AS and became visible by dye-staining AS, were observed in unstable angina or non-ST elevation myocardial infarction patients but not in ST-elevation myocardial infarction patients [12].

Coronary in-stent thrombosis is not infrequently observed by AS even 6 months or over after stenting, despite the use of ticlopidine and aspirin. However, the mechanisms underlying this late thrombosis are not well known. Endothelial cells are highly antithrombotic. Therefore, there is a possibility that neoendothelial cells covering stent struts are damaged.

The present authors carried out angioscopic observation of the coronary segments 6 months after bare stent implantation in 44 patients. Stent struts were classified by conventional AS into subgroups: stent struts not covered by neointima (naked group), stent struts seen through the neointima (seen-through group), and those not seen through the neointima (not-seen-through group). Endothelial damages visualized by EB were observed in 13.3 % of not-seen-through group, while in 80 % of seen-through and naked groups (Fig. 3.5).The neoendothelial cells covering stent struts in the seen-through/naked group were stained blue with EB more frequently than in the not-seen-through group, indicating neoendothelial cell damage (Fig. 3.6). Neoendothelial cell damage was classified into localized damage or diffuse damage. Late stent thrombosis was observed in the latter type. In animals, late stent thrombosis was observed when the neointima thickness was within 100 μm. Neoendothelial cells may have been damaged by friction between them and the stent struts due to thin interposed neointima which might have acted as a cushion, resulting in the formation of late stent thrombosis [2, 7]. These findings suggest necessity of appropriate thickening of neointima for prevention of late stent thrombosis. Similar mechanism may participate in late stent thrombosis in patients to whom drug-eluting stent was implanted.

There are a considerable number of patients with ACS in whom no significant coronary obstructions are angiographically demonstrable. Hitherto, coronary spasm or accidental thrombosis was considered as underlying mechanism, however, without definite evidence. The present authors noticed that there is a certain group of patients with ACS in whom significant stenosis is not demonstrable and the suspected culprit coronary segment exhibits fluffy (or frosty glass-like) surface. In a few of these patients, a thrombus distal to the fluffy segment was detected. The fluffy surface was stained blue with EB, indicating the presence of fibrin and/or damaged endothelial cells (Fig. 3.7).