Characterization of coronary fibrin thrombus in patients with acute coronary syndrome using dye-staining angioscopy.

OBJECTIVE: Because fibrin is transparent and almost invisible by any conventional imaging methodologies, clinical examinations of coronary fibrin thrombus have been ignored, and little is known about its role in the genesis of acute coronary syndrome (ACS). The present study was performed to visualize coronary fibrin thrombus and to examine its role in ACS. METHODS AND RESULTS: Dye-staining coronary angioscopy using Evans blue dye, which selectively stains fibrin blue but does not stain blood corpuscles, was performed for observation of globular coronary thrombi in 111 ACS patients. The thrombi were aspirated for histological examination. The thrombi were classified by visual appearance into 8 transparent, 3 light-red, 2 frosty glass-like and membranous, 32 white, 8 brown, 34 red, and 19 red-and-white in a mosaic pattern. Transparent thrombi that were not visible by conventional angioscopy were visualized as a blue structure by dye-staining angioscopy, and they were observed in patients with unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI). The thrombi caused total or subtotal coronary occlusion. The aspirated thrombi were composed of fibrin alone by histology. Fibrin-rich thrombi were visualized using dye-staining angioscopy in 60% of 50 patients with UA+NSTEMI and in 29% of 61 patients with ST-elevation myocardial infarction. By histology of the aspirated thrombi, fibrin-rich thrombi were observed in 71% of 33 patients with UA+NSTEMI and in 28% of 35 patients with ST-elevation myocardial infarction. CONCLUSION: Fibrin-rich coronary thrombi were frequently observed by both dye-staining angioscopy and histology in ACS patients. Rarely, fibrin itself formed a globular thrombus and caused coronary occlusion.

Cardioscopic detection of left ventricular thrombi. -With special reference to a comparison with left ventriculography and echocardiography-.

BACKGROUND: Thrombosis occurs in the left ventricle and causes ischemic cerebral attacks. However, differences in the incidence of left ventricular thrombi (LVT) among various categories of heart diseases are not known. METHODS AND RESULTS: From April 2000 to 31 March 2008, 258 patients (104 females and 154 males; age 63 ± 6 years) with a heart disease underwent cardioscopy of the left ventricle. LVT were detected by cardioscopy in 78 of 258 patients; 12.5% of 57 patients with stable angina, 0% of 9 with unstable angina, 45.2% of 42 with acute myocardial infarction, 23.2% of 43 with old myocardial infarction, 61.9% of 21 with idiopathic acute myocarditis, 44.3% of 68 with idiopathic chronic myocarditis, 33.3% of 6 with rheumatic valvular disease, 25.7% of 31 with idiopathic dilated cardiomyopathy and in 8.0% of 12 with idiopathic hypertrophic cardiomyopathy. Nine of 78 thrombi were globular and 69 were mural. The detection rate of LVT by cardioscopy, left venticulography, non-contrast and contrast echocardiography was 30.2%, 2.7%, 1.9% and 7.0%, respectively. CONCLUSIONS: LVT were frequently detected by cardioscopy in patients with heart diseases. Although invasive, cardioscopy was more sensitive in detecting LVT than left ventriculography, and non-contrast and contrast echocardiography.

Cardioscopic observation of subendocardial microvessels in patients with coronary artery disease.

Coronary microvessels play a direct and critical role in determining the extent and severity of myocardial ischemia and cardiac function. However, because direct observation has never been performed in vivo, the functional properties of the individual microvesssels in patients with coronary artery disease remain unknown. Subendocardial coronary microvessels were observed by cardioscopy in 149 successive patients with coronary artery disease (81 with stable angina and 68 with old myocardial infarction). Twenty-four arterial microvessels (AMs) and 27 venous microvessels (VMs) were observed in the left ventricular subendocardium. All 12 AMs and 13 of 14 VMs that were located in normokinetic-to-hypokinetic left ventricular wall segments were filled with blood during diastole and were collapsed during systole. In contrast, 8 of 12 AMs and 9 of 13 VMs that were located in akinetic-to-dyskinetic wall segments were filled with blood during systole and were collapsed during diastole. There were no significant correlations between the timing of blood filling and the severity of coronary stenosis and collateral development. In patients with coronary artery disease, the timing of blood filling of AMs and VMs was dependent on the regional left ventricular contractile state; during diastole when contraction was preserved and during systole when it was not. It remains to be elucidated whether and how blood filling is disturbed in other categories of heart disease.

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.

Nitroglycerin-induced heterogeneous subendocardial myocardial blood flow observed by cardioscopy in patients with coronary artery disease.

It is controversial as to whether or not nitroglycerin (NTG) increases subendocardial myocardial blood flow (SMBF), and if it does, whether arterial or venous blood flow is increased in patients with coronary artery disease. This study was performed to examine NTG-induced changes in SMBF.Changes in SMBF induced by NTG (200 µg, i.v.) were examined by cardioscopy in 58 left ventricular wall segments of 58 patients with coronary artery disease. NTG-induced red and purple endocardial colors were defined as increased arterial and venous SMBF, respectively. Endocardial color before NTG administration was classified into brown, light brown, pale and white. Endomyocardial biopsy of the observed portion and (201)Tl scintigraphy were performed in 40 of these patients immediately after cardioscopy and several days after cardioscopy, respectively.Upon administration of NTG, SMBF increased in 48 of 58 wall segments; arterial SMBF in 34 and venous SMBF in 12 wall segments; arterial SMBF in all 24 brown to light brown segments; venous SMBF, arterial SMBF and no change in 12, 10 and 5 of pale segments, respectively; and no change in all 10 white wall segments. (201)Tl-scintigraphy and endomyocardial biopsy revealed that brown, light brown, pale and white endocardial color represented no ischemia, mild ischemia, severe ischemia and fibrosis, respectively.NTG caused an increase in either arterial or venous SMBF depending on control endocardial color, wall motion and severity of coronary stenosis.

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.

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.

Formation of web- and membrane-like structures on the edges of bare-metal coronary stents.

BACKGROUND: Web-like (W) and membrane-like (M) structures have been observed on coronary stent edges on angioscopy but their incidence and mechanisms remain obscure. METHODS AND RESULTS: First, 26 patients [acute coronary syndromes (ACS) in 10 and stable angina (SA) in 16] underwent angioscopy of the stented coronary artery immediately after, and 32 patients (ACS in 18 and SA in 14) 6 months after insertion of bare-metal stents. Second, angioscopy of the stented coronary artery was performed in 4 beagles 5 h after, and in 9 beagles 1 month after stenting. W and M were observed in patients with ACS and those with SA (80.0% vs 18.7%; P<0.05) immediately after and 6 months after stenting (55.5% vs 28.5%; NS). They were stained with Evans blue that selectively stains fibrin immediately after stent insertion, but not 6 months later. In beagles, W and M were observed in 75.0% at 5 h and in 66.6% 1 month later. Histologically, W and M were composed of fibrin at 5 h, whereas they were composed of collagen fibers at 1 month. CONCLUSIONS: W and M were frequently formed on the edges of coronary stents. They were formed with fibrin in the acute phase, whereas this fibrin was replaced by collagen fibers in the chronic phase.

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.

Imaging of subendocardial myocardial blood flow by dye-staining cardioscopy in patients with coronary artery disease.

This study was carried out to image subendocardial myocardial blood flow (SMBF) by dye-staining cardioscopy (DSC) in patients with coronary artery disease.In patients with epicardial coronary artery disease, SMBF plays a direct and critical role in determining the extent and severity of cardiac function and symptoms. If SMBF could be clinically imaged instantaneously, the effects of medical and interventional treatment on it can be directly evaluated. However, there are no clinically available methods for direct and real-time imaging of SMBF. Twenty-three patients [6 with chest pain syndrome (CPS); 3 with vasospastic angina pectoris (VSA); 9 with angina pectoris due to organic coronary stenosis (AP); 5 with old myocardial infarction OMI)] underwent DSC of the left ventricle by selective intracoronary injection of 1 mL of 2.5% Evans blue dye solution (EB). Five patients with acute myocardial infarction (AMI) underwent DSC before and after coronary stent deployment. The endocardial surface was stained diffusely blue with EB indicating normal blood flow in patients with CPS; stained in a patchy fashion indicating patchy blood flow in patients with VSA; and stained in a patchy fashion or not stained indicating patchy or no blood flow in those with AP and OMI. Myocardial staining with EB was observed after coronary stent deployment in all patients with AMI, indicating restoration of the SMBF. It is evident that SMBF could be imaged by DSC. This imaging modality is useful for the evaluation of therapies and accurate guidance of transendocardial therapies of the ischemic myocardium.

Association between preheparin serum lipoprotein lipase mass and acute myocardial infarction in Japanese men.

A sensitive immunoassay system using a specific monoclonal antibody against lipoprotein lipase (LPL) recently demonstrated the presence of an LPL mass in preheparin serum. We reported that a preheparin serum LPL mass (pre-LPL mass) reflected the level of functioning LPL activity in the whole body and could be deeply involved in the progression of coronary atherosclerosis of stable organic angina pectoris. We examined the relation between the pre-LPL mass and acute myocardial infarction (AMI). We studied 44 males with AMI (AMI group) and 16 males with a normal coronary artery (NCA group), and measured the pre-LPL mass by enzyme-linked immunosorbent assay. Coronary risk factors including the pre-LPL mass were compared between the two groups and multiple regression analysis was performed for AMI. There were no significant differences in the lipid data, but the pre-LPL mass level was significantly low in the AMI group (52 +/- 16 vs 41 +/- 14 ng/ml, p = 0.01), and a low pre-LPL mass concentration was observed in the small sized LDL group and/or the Midband positive group. Multiple regression analysis revealed that a low pre-LPL mass and hypertriglyceridemia were independent risk factors for AMI (t value = 2.1, 2.4). The result indicates that a low pre-LPL mass may be an important risk factor for AMI and stable organic angina pectoris.

Relationship between cardioscopic images and histological changes in the left ventricle of patients with idiopathic myocarditis.

AIMS: Endomyocardial biopsy is essential for definite diagnosis of idiopathic myocarditis. However, since endomyocardial biopsy is guided by fluoroscopy, whether or not the diseased myocardium is biopsied depends on chance, and this may lead to misdiagnosis. If the endocardial surface represents changes indicative of stages of myocarditis, staging of myocarditis and targeted cardioscope-guided biopsy could be used for accurate histological diagnosis. METHODS AND RESULTS: The relationship between left ventricular endocardial surface colour observed by cardioscopy and biopsy findings were examined in 78 patients with suspected idiopathic myocarditis. Of these, 59 patients were diagnosed histologically as idiopathic myocarditis. Endocardial colour was classified into red, milky white, purple, yellowish brown, or white. Biopsied specimens with red and milky white wall segments exhibited histological changes compatible with acute myocarditis; purple segments, active chronic myocarditis; and yellowish brown and white segments, inactive chronic myocarditis. The sensitivity, specificity, and predictive value of red and milky white colours for detecting acute myocarditis were 100, 100, and 100%, respectively; of purple for detecting active chronic myocarditis were 83, 92, and 78%, respectively; and yellowish brown and white for detecting inactive chronic myocarditis were 82, 74, and 53, respectively. CONCLUSION: Red and milky white endocardial surface colours predicted histological acute myocarditis, and purple predicted active chronic myocarditis. However, yellowish brown and white colours did not predict inactive chronic myocarditis.

Evaluation of myocardial tissue fluid flow by fluorescence cardioscopy in patients with coronary artery disease.

Myocardial tissue fluid flow (MTFF) directly represents the oxygen supply to the cardiomyocytes. Therefore, imaging of MTFF is carried out by fluorescence cardioscopy (FC).Sixty-six patients with coronary artery disease underwent FC using fluorescein as an indicator of MTFF because this dye exhibits fluorescence in tissue fluid but not in the blood. Three mL of 10% fluorescein was injected intravenously and fluorescence images of the left ventricular endocardial surface were obtained by FC at 30 seconds and 1, 3 and 6 minutes later to evaluate the MTFF.The CF images were classified as follows: diffuse with high intensity indicating normal MTFF; diffuse but with low intensity indicating decreased MTFF, no fluorescence indicating absent MTFF, and patchy fluorescence indicating patchy preservation of MTFF. MTFF was normal in all 18 patients with chest pain syndrome, patchy fluorescence was decreased or absent in 16 of 20 patients with angina and/or old myocardial infarction due to organic coronary artery disease, and was patchy in 21 of 28 patients with vasospastic angina. Ten of these 20 patients underwent coronary stenting with successful angiographic results in all. However, MTFF disturbance frequently remained.FC is clinically feasible for evaluation of MTFF disturbance, for evaluation of even emergency coronary interventions, and for guidance of transendocardial angiogenic and myogenic therapies in patients with coronary artery disease.

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.

[Study of the echocardiographic diagnosis of acute pulmonary thromboembolism and risk factors for venous thromboembolism].

OBJECTIVES: To identify the relationship of risk factors for atherosclerosis with venous thromboembolism (VTE) and the utility of transthoracic echocardiography in acute pulmonary thromboembolism (APTE). METHODS: In 75 patients with VTE (VTE group), 101 patients with suspected VTE (N group), and 50 control subjects (control group), the frequency of atherosclerosis risk factors such as hyperlipidemia, obesity, hypertension, smoking, and diabetes mellitus and the number of risk factors were evaluated. Transthoracic echocardiographic findings such as tricuspid regurgitation, right ventricular dilation, pulmonary hypertension, and right ventricular dysfunction were evaluated in 15 patients with APTE (APTE group) and 38 patients in the N group (NC group). RESULTS: The incidence of hyperlipidemia in the VTE group was statistically higher than that in the control group (odds ratio 2.16, 95% confidence interval 1.43-3.08). Additionally, the incidence of obesity was higher in the VTE and N groups than in the control group (odds ratio was 2.76, 95% confidence interval 1.67-4.37). Risk factors other than obesity and hyperlipidemia and the number of risk factors were not significant. The incidence of tricuspid regurgitation, right ventricular dilation, and pulmonary hypertension in APTE was statistically greater than that in NC group. Right ventricular dilation and right ventricular dilation + tricuspid regurgitation are reliable findings in echocardiography. However, even combining with tricuspid regurgitation, right ventricular dilation is insufficient to identify or screen patients with APTE. CONCLUSIONS: Hyperlipidemia and obesity may be risk factors for VTE. However, obese patients can manifest similar findings to VTE. Although transthoracic echocardiograpghy is not recommended as a diagnostic or screening test in APTE, it should be used as an ancillary test.

[Headache due to nitroglycerin administration and its clinical significance].

OBJECTIVES: This study assessed the side effects of nitroglycerin administration and their clinical significance. METHODS: Adverse reactions associated with sublingual nitroglycerin administration were investigated in 103 patients, 71 men and 32 women (mean age 56 +/- 11 years), 32 patients with coronary artery stenosis and 71 without coronary artery stenosis. RESULTS: Fifty-one percent of patients experienced headache and 30% experienced other adverse reactions, whereas 19% experienced no adverse reactions. The relationship was investigated between headache, the most common adverse reaction, and the following eight clinical background factors: coronary angiographic findings, sex, age, hyperlipidemia, hypertension, diabetes mellitus, smoking and drinking. Multiple regression analysis was conducted by treating sublingual nitroglycerin-induced headache as an object variable and the clinical background factors as explanatory variables. Statistically, the onset of headache correlated most closely to coronary angiographic findings, followed by smoking, hypertension, diabetes mellitus and drinking. The first four factors suppressed the onset of headache, whereas drinking facilitated the onset of headache. CONCLUSIONS: There is a close relationship between the onset of headache following sublingual nitroglycerin administration and coronary angiographic findings. Sublingual nitroglycerin-induced headache as a predictor of coronary angiographic findings has a sensitivity and specificity of 81% and 66%, respectively, for patients without coronary artery stenosis based on the absence of headache.

[Relationship between insulin resistance and oxidative stress in vivo].

OBJECTIVES: The relationship between oxidative stress in vivo and insulin resistance was examined. METHODS: This study included 87 patients, 46 males and 41 females (mean age 63 +/- 10 years), without coronary artery disease. The homeostasis assessment insulin resistance (HOMA-IR) (fasting blood sugar x fasting immunoreactive insulin/405), a marker for insulin resistance, was measured. The patients were divided into three groups: the noninsulin resistance group (N-IR group) without diabetes mellitus (DM) and with fasting blood glucose level of 126 mg/dl and HOMA-IR < or = 1.73 (n = 44), the insulin resistance group (IR group) without diabetes mellitus and with fasting blood glucose level of 126 mg/dl and HOMA-IR > 1.73 (n = 29), and the DM group (type 2 diabetes mellitus) (n = 14). Urinary 8-iso-prostaglandin F2 alpha (U-8-iso-PGF2 alpha) excretion was measured as a marker of in vivo oxidative stress. RESULTS: There were significantly more obese patients in the IR group than in the N-IR group (62% vs 25%, p = 0.001), and the remnant-like particle cholesterol level was significantly higher in the IR group than in the N-IR group (7.6 +/- 5.2 vs 4.6 +/- 1.5 mg/dl, p < 0.01). Patients in the IR group had a significantly larger number of coronary risk factors. U-8-iso-PGF2 alpha excretion was significantly higher in the IR group and DM groups (201 +/- 86, 191 +/- 136 vs 129 +/- 50 pg/mg. Cr, p < 0.0001, p = 0.01), and there was a significantly positive correlation between the number of coronary risk factors, fasting blood sugar and U-8-iso-PGF2 alpha concentration (correlation coefficient = 0.32, 0.37, p = 0.002, p = 0.0003). Multiple regression analysis showed that remnant-like particle cholesterol, fasting blood sugar and insulin resistance were independent factors for U-8-iso-PGF2 alpha concentration (p < 0.0001, p = 0.0007, p = 0.02). CONCLUSIONS: Insulin resistance, remnant lipoprotein and hyperglyceridemia are deeply involved in oxidative stress in vivo.

Preventive effect of an antiallergic drug, pemirolast potassium, on restenosis after stent placement: quantitative coronary angiography and intravascular ultrasound studies.

OBJECTIVES: The preventive effect of pemirolast against restenosis after coronary stent placement was evaluated. METHODS: Eighty-four patients with 89 de novo lesions who underwent successful coronary stenting were assigned to the pemirolast group(40 patients, 45 lesions) and the control group(44 patients, 44 lesions). Administration of pemirolast(20 mg/day) was initiated from the next morning after stenting and continued for 6 months of follow-up. Quantitative coronary angiography was performed immediately after stenting and at follow-up. Angiographic restenosis was defined as diameter stenosis > or = 50% at follow-up. Intravascular ultrasound study conducted at follow-up angiography was used to measure vessel cross-sectional area(CSA), stent CSA, lumen CSA, neointima CSA(stent CSA--lumen CSA), and percentage neointima CSA(neointima CSA/stent CSA x 100%) at the minimal lumen site. RESULTS: There were no significant differences in baseline characteristics between the two groups. Restenosis rate was significantly lower in the pemirolast group than in the control group(15.0% vs 34.1% of patients, 13.3% vs 34.1% of lesions, p < 0.05, respectively). The intravascular ultrasound study at follow-up(36 lesions in the pemirolast group, 33 in the control group) found no significant differences in vessel CSA and stent CSA between the two groups(17.3 +/- 2.2 vs 16.8 +/- 2.4 mm2, 8.6 +/- 1.9 vs 8.4 +/- 1.7 mm2, respectively). However, lumen CSA was significantly larger in the pemirolast group than in the control group(5.5 +/- 1.3 vs 4.4 +/- 1.1 mm2, p < 0.05). Moreover, neointima CSA and percentage neointima CSA were significantly smaller in the pemirolast group(3.1 +/- 1.1 vs 4.0 +/- 1.2 mm2, p < 0.05 and 36.2 +/- 15.9% vs 47.4 +/- 15.6%, p < 0.01). CONCLUSIONS: Pemirolast has a preventive effect against restenosis after stent placement, possibly by inhibiting neointimal hyperplasia.

[Clinical significance of preheparin serum lipoprotein lipase mass in normocholesterolemic patients with coronary artery disease].

OBJECTIVES: Some normocholesterolemic patients have coronary artery disease (CAD) in Japan. This study evaluated the clinical significance of preheparin lipoprotein lipase mass as a risk factor for normocholesterolemic patients with CAD. METHODS: This study included 89 normocholesterolemic male patients with CAD (CAD group, 40 with stable organic angina pectoris, 19 with vasospastic angina pectoris, and 30 with acute myocardial infarction), and 13 normocholesterolemic males with normal coronary arteries (control group) with no stenotic lesion and negative reaction to intracoronary administration of acetylcholine. Preheparin lipoprotein lipase mass was measured by enzyme-linked immunosorbent assay. Coronary risk factors including preheparin lipoprotein lipase mass were compared between the two groups. Low-density lipoprotein (LDL) particle size and presence of midband were estimated by polyacrylamide gel disc electrophoresis. RESULTS: Mild hypertriglyceridemia and low high-density lipoprotein (HDL) cholesterolemia were observed in the CAD group, and small particle size LDL and presence of midband were also common in the CAD group. Preheparin lipoprotein lipase mass level was significantly lower in the CAD group than the control group (52 +/- 18 vs 40 +/- 13 ng/ml, p = 0.005) as well as in each type of patient in the CAD group. Multiple regression analysis showed that small particle size LDL, low preheparin lipoprotein lipase mass and smoking were independent risk factors for CAD (p < 0.001, p = 0.007, p = 0.037). Low preheparin lipoprotein lipase mass concentration was observed in the small particle size LDL group and/or the midband positive group. CONCLUSIONS: These results indicate that low preheparin lipoprotein lipase mass reflects insulin resistance and may be deeply involved in the progression of coronary arteriosclerosis.