Isao Yaguchi

Comparison of activation process of platelets and neutrophils after coronary stent implantation versus balloon angioplasty for stable angina pectoris

The pathophysiologic features of stent-induced cellular responses of platelets and leukocytes have not been established. This study was designed to clinically investigate the activation of platelets and neutrophils after coronary stenting and to identify its effects on the long-term results of coronary stents. Forty-eight consecutive patients with left anterior descending coronary artery disease indicating coronary intervention were randomly assigned to either a balloon angioplasty group or a coronary stent group. Flow cytometric analysis demonstrated that the transcardiac gradient (the value of coronary sinus blood minus the value of peripheral blood) of platelet surface expression of CD62P (p < 0.001) and CD63 (p < 0.01) increased immediately after coronary stenting, but increased less significantly immediately after balloon angioplasty (CD62P, p < 0.01; CD63, p < 0.05). These increases were persistently observed after coronary stenting but transiently after balloon angioplasty alone during a 48-hour observation period after the procedures. The gradient for neutrophil surface expression of CD11b increased, and that of CD62 L decreased 48 hours after coronary stenting (CD11b, p < 0.001; CD62 L, p < 0.05), but these changes showed less significance 48 hours after balloon angioplasty alone (CD11b, p < 0.05; CD62 L, p = NS). The gradients 48 hours after the procedures for both CD62P (r = 0.39, p < 0.05) and CD11b (r = 0.44, p < 0.01) were independently correlated with the late loss in the stent group, whereas the correlation was seen only for CD11b (r = 0.38, p < 0.05) in the balloon angioplasty group. Both platelet and neutrophil activation was greater after coronary stenting than after balloon angioplasty. Cellular interactions between platelets and neutrophils may be related to the progression of neointimal proliferation leading to restenosis after coronary stent implantation.

Lower Expression of Neutrophil Adhesion Molecule Indicates Less Vessel Wall Injury and Might Explain Lower Restenosis Rate After Cutting Balloon Angioplasty

BACKGROUND The Cutting Balloon is a novel dilatation catheter for coronary angioplasty (InterVentional Technologies Inc). It produces longitudinal, microsurgical incisions in the vessel wall before the actual dilatation. It is assumed that these controlled surgical incisions relieve hoop stress and reduce vessel wall injury and eventually restenosis. However, no clinical indicator to support the theory of reduced injury has been described. Certain clusters of differentiation (eg, CD11, CD18 on the leukocytes) are implicated in leukocyte adhesion, increased permeability, and opsonization. Therefore, they might serve as clinical indicators of the injury level of the vessels after angioplasty. METHODS AND RESULTS We randomly selected 64 patients with isolated left anterior descending coronary artery disease for either Cutting Balloon angioplasty or conventional balloon angioplasty. The expression of CD18 and CD11b on the surface of neutrophils was determined by flow cytometric analysis. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) were also measured. The expression of both the CD18 and CD11b in the coronary sinus blood gradually increased and reached its maximum at 48 hours after angioplasty. The sICAM-1 levels in the coronary sinus serum also increased after angioplasty. Percentage increases of CD18 and CD11b expression and the increase of the sICAM-1 levels at 48 hours after angioplasty (as ratios to baseline values before angioplasty) were less in the Cutting Balloon angioplasty group than in the conventional balloon angioplasty group (CD18, 1.10+/-0.05 versus 1.31+/-0.05, P<0.05; CD11b, 1.23+/-0.06 versus 1.72+/-0.10, P<0.001; sICAM-1, 1.12+/-0.05 versus 1.25+/-0.02, P<0.05). In all patients, the late lumen loss at follow-up angiogram positively correlated with the increased levels of CD11b (R=0.59, P<0.001) and sICAM-1 (R=0.38, P<0.05) at 48 hours after angioplasty. CONCLUSIONS Balloon angioplasty upregulated Mac-1 (CD11b/CD18) on the surface of the neutrophils and increased sICAM-1 levels in association with late loss increase. These changes were significantly smaller in the Cutting Balloon angioplasty group than in the conventional balloon angioplasty group. This suggests that Cutting Balloon angioplasty may produce less vessel wall injury and, consequently, less neutrophil activation, which may account for the lower rate of restenosis.

Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis.

Background—Increased expression of the &bgr;2 integrin Mac-1 (CD11b/CD18, &agr;M&bgr;2), which is responsible for firm leukocyte adhesion to platelets and fibrinogen at injured vessels, is found in association with neointimal hyperplasia after coronary interventions. The role of Mac-1 in the pathophysiology of restenosis is incompletely defined. To clarify further the role of Mac-1, we determined whether coronary stenting induced activation of Mac-1, which is required for high-affinity receptor-ligand interactions. Methods and Results—Expression of CD11b (&agr;-subunit of Mac-1) and binding of 8B2 (monoclonal antibody against an activation-dependent neoepitope of Mac-1) on the surface of polymorphonuclear leukocytes were analyzed in 62 patients undergoing coronary stenting using flow cytometric analysis of whole blood obtained from the coronary sinus and femoral vein. Transcardiac CD11b expression increased significantly at 24 hours and maximally at 48 hours after stenting; 8B2 began to increase at 10 minutes and was maximally increased at 48 hours after stenting. These changes were more prominent in patients with subsequent restenosis. Multiple regression analysis showed that the late lumen loss by quantitative coronary angiographic analysis was independently correlated with the CD11b increase (R =0.42, P <0.01) and the 8B2 increase (R =0.55, P <0.001) 48 hours after the procedure. Mac-1 activation, as assessed by 8B2 binding, was the most powerful predictor of late lumen loss. Conclusion—Coronary stenting produced upregulation and early activation of the leukocyte integrin Mac-1, which is associated with late lumen loss and restenosis. These data support a role for inflammation in neointimal thickening and suggest the validity of targeting leukocyte recruitment for preventing clinical restenosis.

Impaired endothelium-dependent acetylcholine-induced coronary artery relaxation in patients with high serum remnant lipoprotein particles

Acetylcholine (Ach)-induced vascular relaxation is mediated by nitric oxide released from the endothelium. Hence, impaired Ach-induced relaxation reflects endothelial dysfunction. The action of lipoprotein lipase on chylomicrons and very low density lipoproteins produces remnant lipoproteins (RLP) rich in triglycerides (TG), cholesterol (C) and apolipoprotein E (apo E). Apo E on RLP serves as a ligand for uptake of RLP by macrophages, endothelial cells and other cells expressing the LDL receptor or the remnant receptor; uptake of RLP by vascular wall cells can promote atherosclerosis. Serum C, TG, Lp(a), apo E, apo A-I, apo B, HDL-C and RLP-C were measured in 652 patients who underwent diagnostic coronary angiography. Of these, 48 (32 males and 16 females, age 59 +/- 10 years) were suspected of having ischaemic heart disease because they had chest pain, but without angiographic evidence of atherosclerotic coronary artery disease defined as a discrete stenosis or intimal irregularity, and without any other known underlying heart disease. These were selected for acetylcholine provocation test in the left coronary artery. Nineteen of 48 patients had high RLP-C ( > or = 5 mg/dl, mean 8.7 +/- 3.1 mg/dl), 29 had normal RLP-C ( < or = 5 mg/dl, mean 2.4 +/- 0.4 mg/dl, P < 0.0001). The percent change (-, constriction, or +, dilation) in coronary artery diameter after intracoronary injection of Ach was smaller in the high RLP-C group, compared with the normal RLP-C group thus, in the left anterior descending artery, -33 +/- 23 vs -8 +/- 25 in the proximal segment (P <0.01), -30 +/- 37 vs -3 +/- 29 in the mid segment (P < 0.01), -17 +/- 47 vs 16 +/- 43 in the distal segment (P < 0.001); in the left circumflex artery, -29 +/- 46 vs -9 +/- 28 in the proximal segment (P < 0.01), -29 +/- 43 vs -5 +/- 34 in the mid segment (P < 0.01), -26 +/- 43 vs 10 +/- 31 in the distal segment (P < 0.001). There were no significant differences in other lipid levels. These results suggest that there is an association between high serum RLP-C and coronary vascular endothelial cell dysfunction and that RLP-C may be taken as a marker of early stage coronary artery atherosclerosis not detectable by angiography.

Serum Levels of Circulating Adhesion Molecules after Coronary Angioplasty

The activation of platelets, leukocytes, and vascular endothelial cells mediated by cell adhesion molecules may play a role in the mechanism of restenosis, which is still a significant complication after coronary angioplasty. We observed serial changes in the circulating soluble forms of adhesion molecules in 25 patients with coronary artery disease who underwent coronary angioplasty for a single lesion of the left anterior descending artery. Serum levels of sICAM-1 (p < 0.05) and sP-selectin (p < 0.05) were significantly increased immediately after angioplasty in the coronary sinus blood samples. These increases continued during the 48-hour observation period, and the maximum increase was seen 48 h after angioplasty for sICAM-1 (p < 0.01) and 24 h after angioplasty for sP-selectin (p < 0.01). The level of sL-selectin increased 24 h (p < 0.01) and 48 h (p < 0.001) after angioplasty. These changes were not observed in the peripheral blood samples. The sE-selectin level did not change after angioplasty. A multiple regression analysis showed that the late loss index obtained from quantitative angiographic (QCA) analysis was correlated with the changes in sICAM-1 (r = 0.31, p < 0.05), sL-selectin (r = 0.28, p < 0.05), and sP-selectin (r = 0.26, p < 0.05) 48 h after angioplasty in the coronary sinus blood samples, but was not correlated with procedural variables, other QCA variables, or the change in the sL-selectin level. The measurements of these adhesion molecule levels may help to evaluate traumatic vessel wall injury and inflammation at the intervention site after coronary angioplasty.

Clinical Significance of the Antibody against Oxidized Low-Density Lipoprotein in Acute Myocardial Infarction

To establish the clinical significance of the antibody against oxidized low-density lipoprotein (anti-Ox-LDL) titer in patients with acute myocardial infarction (AMI), we measured the anti-Ox-LDL titer in 39 patients with AMI and 25 controls. In all AMI patients, the anti-Ox-LDL titer on admission was higher (p < 0.05) than the value in the controls. One month after admission, the titer decreased significantly (p < 0.001) reaching control levels. In patients who underwent thrombolytic therapy, the anti-Ox-LDL titer on admission was identical in patients with occluded infarct-related arteries (IRA) and patients with patent IRA during emergency coronary angiography. In patients who did not undergo thrombolytic therapy, the anti-Ox-LDL titer on admission was higher in patients with occluded IRA than in patients with patent IRA. An increased anti-Ox-LDL titer may be a risk factor for the onset of AMI. Spontaneous recanalization of the IRA may be associated with increased anti-Ox-LDL titers, while thrombolysis-induced recanalization may be independent of it.

Air embolism in the right coronary artery occurring during the left coronary angioplasty using the guiding catheter with a side hole

Coronary air embolism is one of the inadvertent complications of coronary angioplasty. We report two rare cases of complicating air embolism in the right coronary artery occurring during control left coronary angiography using a guiding catheter with a side hole, just prior to a coronary intervention procedure for a left coronary artery lesion. The air seemed to be injected into the right coronary artery through the side hole. When we use an angiographic or guiding catheter with a side hole, we should be aware that an air embolism can occur in the contralateral coronary artery and should carefully and repeatedly perform aspiration of the catheter. Cathet. Cardiovasc. Intervent. 49:331–334, 2000.

Impact of Insulin Resistance on Neointimal Tissue Proliferation after 2nd-Generation Drug-Eluting Stent Implantation

Percutaneous coronary intervention is established as an effective treatment for patients with ischemic heart disease; in particular, drug-eluting stent implantation is known to suppress in-stent restenosis. Diabetes mellitus is an independent risk factor for restenosis, so reducing insulin resistance is being studied as a new treatment approach. In this prospective study, we sought to clarify the factors associated with in-stent restenosis after percutaneous coronary intervention, and we evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) index as a predictor of restenosis. We enrolled 136 consecutive patients who underwent elective percutaneous coronary intervention at our hospital from February 2010 through April 2013. All were implanted with a 2nd-generation drug-eluting stent. We distributed the patients in accordance with their HOMA-IR index values into insulin-resistant Group P (HOMA-IR, ≥2.5; n=77) and noninsulin-resistant Group N (HOMA-IR, <2.5; n=59). Before and immediately after stenting, we measured reference diameter, minimal lumen diameter, and percentage of stenosis, and after 8 months we measured the last 2 factors and late lumen loss, all by means of quantitative coronary angiography. After 8 months, the mean minimal lumen diameter was smaller in Group P than that in Group N (1.85 ± 1.02 vs 2.37 ± 0.66 mm; P=0.037), and the mean late lumen loss was larger (0.4 ± 0.48 vs 0.16 ± 0.21 mm; P=0.025). These results suggest that insulin resistance affects neointimal tissue proliferation after 2nd-generation drug-eluting stent implantation.

A Case of Double-Chambered Right Ventricle Associated with an Interventricular Septal Aneurysm in an Elderly Patient

Double-chambered right ventricle is a congential malformation caused by an anomalous muscle band obstructing the right ventricular outflow tract. Most reported cases of this condition have been diagnosed in infants, or adolescents. We encountered a 61-year-old woman with a double-chambered right ventricle, associated with a large interventricular septal aneurysm, which is a rare complication. The right ventricular obstruction was corrected with surgery.

Successful transcatheter coil embolisation of a giant coronary artery fistula

A 71-year-old woman came to our hospital with chest pain. A computed tomography revealed right coronary dilatation and a giant fistula (6×12 cm). The fistula was seen to drain from the right coronary artery to the coronary sinus (figure 1A). Figure 1 (A) Computed tomography revealing right coronary dilatation …