Yoshiharu Fujimori

Percutaneous coronary angioscopy in patients with ischemic heart disease

Percutaneous transluminal coronary angioscopy was performed during routine coronary angiography in seven patients and during PTCA in one patient with ischemic heart disease. A flexible fiberscope with an external diameter of 1.4 mm was introduced through an 8F or 9F guiding catheter used for PTCA into the coronary arteries. Warmed saline solution (15 to 20 ml) was injected through the guiding catheter into the coronary arteries for replacement of blood. Twenty-one of the 31 coronary segments were visualized and photographed on color cinefilms. The lumen of the atherosclerotic segment showed narrowing with smooth surface or with spiral folds. PTCA caused dilatation of the stenosed segment with scattered thin thrombi. These findings indicate the usefulness of angioscopy to observe luminal changes in the coronary arteries of patients with ischemic heart disease.

Nonselective Cation Currents Regulate Membrane Potential of Rabbit Coronary Arterial Cell Modulation by Lysophosphatidylcholine

Background—The effects of lysophosphatidylcholine (LPC) on electrophysiological activities and intracellular Ca2+ concentration ([Ca2+]i) were investigated in coronary arterial smooth muscle cells (CASMCs). Methods and Results—The patch clamp techniques and Ca2+ measurements were applied to cultured rabbit CASMCs. The membrane potential was −46.0±5.0 mV, and LPC depolarized it. Replacement of extracellular Na+ with NMDG+ hyperpolarized the membrane and antagonized the depolarizing effects of LPC. In Na+-, K+-, or Cs+-containing solution, the voltage-independent background current with reversal potential (Er) of approximately +0 mV was observed. Removal of Cl− failed to affect it. When extracellular cations were replaced by NMDG+, Er was shifted to negative potentials. La3+ and Gd3+ abolished the background current, but nicardipine and verapamil did not inhibit it. In Na+-containing solution, LPC induced a voltage-independent current with Er of approximately +0 mV concentration-dependently. Similar current was recorded in K+- and Cs+-containing solution. La3+ and Gd3+ inhibited LPC-induced current, but nicardipine and verapamil did not inhibit it. In cell-attached configurations, single-channel activities with single-channel conductance of ≈32pS were observed when patch pipettes were filled with LPC. LPC increased [Ca2+]i as the result of Ca2+ influx, and La3+ completely antagonized it. Conclusions—These results suggest that (1) nonselective cation current (INSC) contributes to form membrane potentials of CASMCs and (2) LPC activates INSC, resulting in an increase of [Ca2+]i. Thus, LPC may affect CASMC tone under various pathophysiological conditions such as ischemia.

Percutaneous fiberoptic angioscopy of the cardiac valves

The feasibility of percutaneous translumial angioscopy of the cardiac valves was examined in eight patients with and in 11 patients without valvular disease. In eight of these patients, a guiding balloon catheter (9F) was introduced into the aortic root, a guide wire (0.014 or 0.025 inch) was introduced through the catheter into the left ventricle to prevent dislocation of the catheter, and a fiberscope (1.6 or 4.6F) was advanced to the distal tip of the catheter. The balloon was then inflated with carbon dioxide and was manipulated against the aortic valve; a body temperature heparinized saline was infused through the catheter for observation. Similarly, the balloon catheter was advanced transseptally into the left atrium for observation of the mitral valve in four patients. Also, the balloon catheter was advanced through the right femoral vein into the right atrium for observation of the tricupid valve in three patients. In patients with a normal aortic valve, the aortic cusp surface was smooth and white and the edges were sharp. They opened briskly during systole and coapted each other completely during diastole. In rheumatic aortic regurgitation, the cuspus were thick and blunt and their coaptation insufficiency was observed during diastole. In a patient with rheumatic AS, globular and yellow cusps were observed. Mitral valve leaflets were smooth and white in a patients without mitral valvular disease, while the leaflets were yellow, thick and irregular, and blood regurgitation from the left ventricle into the left atrium could be observed in two patients with rheumatic MSR. The process of opening and closure of a tricuspid valve was also observed in three patients without tricuspid valvular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous fiberoptic angioscopy of the left ventricle in patients with dilated cardiomyopathy and acute myocarditis

Left ventricular luminal changes were examined by percutaneous fiberoptic angioscopy in 13 patients with dilated cardiomyopathy and in four patients with acute myocarditis. Angioscope-guided endomyocardial biopsy was also performed in six patients with dilated cardiomyopathy and in two with acute myocarditis. A balloon-tipped guiding catheter (9F) was introduced through the right femoral artery into the left ventricle, the balloon was inflated, and a 1.6 or 4.3F fiberscope was introduced through the catheter into the ventricle so as to locate the fiberscope tip at the tip of the catheter shaft. The balloon was then pushed against the desired portion of the ventricle and warmed saline was infused to observe the luminal changes. In contrast to the patients without organic heart disease whose left ventricular luminal surface was brown in color, the luminal surface was white or light yellow in four, light brown in one, bluish-white in one, with white and brown portions distributed in a mosaic pattern in four, and it was reddish brown in the remaining one patient with dilated cardiomyopathy. Mural thrombi were observed in two of the patients. The luminal surface was light brown in one, reddish brown in one, rose in one, and red in one patient with acute myocarditis. Thrombi and scattered bleeding were observed in two and one of these patients, respectively. The changes in luminal coloration in patients with dilated cardiomyopathy and acute myocarditis had no obvious relation to left ventricular volume and ejection fraction. Angioscope-guided biopsy revealed that the white and light yellow portions were due to endocardial fibrosis, that the endocardia of brown portions were not fibrotic, and that the myocardium in the red portions contained mononuclear cells, indicating inflammation. The results indicate that the angioscopic features of the left ventricular luminal surface were not uniform in patients with dilated cardiomyopathy or in those with acute myocarditis, and that angioscopy can be used as a guiding tool for endomyocardial biopsy.

Local treatment with antithrombotic drugs can prevent thrombus formation: an angioscopic and angiographic study.

OBJECTIVES This study was designed to evaluate the efficacy of local versus systemic treatment of thrombosis with various antithrombotic drugs. BACKGROUND Local use of low dose antithrombotic drugs has been proposed as being effective and safe. METHODS Heparin (30 U/kg), an antithrombin agent (argatroban, 0.05 mg/kg body weight) or a defibrinogenating drug (batroxobin, 0.05 U/kg) was locally infused into one side of the canine iliac artery after injury by balloon inflation. The other side was injured as a control. The efficacy of systemic delivery of high dose (heparin [300 U/kg] and argatroban [0.5 mg/kg]) and low dose drugs was also assessed. RESULTS Sixty minutes after local treatment in 22 dogs, no thrombotic stenosis was observed by angiography in locally treated arteries (p < 0.005 vs. mean thrombotic stenosis of 27% in control segments for heparin, 25.3% in control segments for argatroban and 32% in control segments for batroxobin). Angioscopy demonstrated the same trend. In locally treated arteries, thrombus weight was significantly lower in the treated than control side. In the systemic high dose group (n = 10), angiographic thrombotic stenosis was < 5% after high dose drug delivery (p < 0.05 vs. control segments, 37.4% for heparin, 43% for argatroban). In another 10 dogs, low dose systemic delivery was not effective in inhibiting thrombus formation. Activated partial thromboplastin time and fibrinogen levels did not change with local treatment. CONCLUSIONS Compared with systemic administration of antithrombotic drugs, local treatment is a safer and more effective method of preventing thrombosis.

Angioscopic Evaluation of Stabilizing Effects of Bezafibrate on Coronary Plaques in Patients With Coronary Artery Disease

Background Since long-term administrations of anti-hyperlipidemic agents result in reduction in % stenosis or increase in minimum lumen diameter (MLD) of stenotic coronary segments, it is generally believed that anti-hyperlipidemic agents stabilize vulnerable coronary plaques. However, recent pathologic and angioscopic studies revealed that vulnerability of coronary plaques is not related to severity of stenosis and the rims rather than top of the plaques disrupt, and therefore, angiography is not adequate for evaluation of vulnerability. Angioscopy enables macroscopic pathological evaluation of the coronary plaques. Therefore, we carried out a prospective angioscopic open trial for evaluation of the stabilizing effects of bezafibrate on coronary plaques. Methods From April, 1997 to December, 1998, 24 patients underwent coronary angioscopy of the plaques in the non-targeted vessels during coronary interventions and 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrat (14 patients, 21 plaques) groups. Oral administration of bezafibrate (Bezatol SR, 400mg/day) was started immediately after the interventions and was continued for 6 months. The vulnerability score was determined based on angioscopic characteristics of plaques and it was compared before and 6 months later. Results Six months later, vulnerability score was reduced (from 1.6 to 0.8;p < 0.05) in bezafibrate group and unchanged (from 1.4 to 1.3; NS) in control group. In bezafibrate group, the changes in vulnerability score was not correlated with those in % stenosis or MLD. Conclusion The results indicate that bezafibrate can stabilize coronary plaques.

Induction of thrombolysis and prevention of thrombus formation by local drug delivery with a double-occlusion balloon catheter

SummaryThe efficacy of the local delivery of an antithrombotic drug in preventing thrombosis and enabling thrombolysis was investigated in 29 dogs. An antithrombotic drug (heparin, 25U/kg), or an antithrombin (argatroban, 0.05 mg/kg) was infused into injured canine iliac arteries, using a double-occlusion balloon catheter, and the preventive effect of the drug was evaluated. Local delivery of low-dose tissuetype plasminogen activator (t-PA; Tisokinase, 50 000 U; Kowa, Nagoya and Asahi Chemical Industries, Fuji, Japan) into thrombosed canine iliac arteries, using the same catheter, or intravenous infusion of low-dose or high-dose t-PA (30 000U/kg), was also performed. Angiographically, stenotic thrombosis was 2% by local delivery of argatroban and 7% by local delivery of heparin (P < 0.01 vs each control; 47% and 51% respectively). Thrombotic stenosis, as observed by angiography, decreased from 91% to 9% after local delivery of t-PA, and from 94% to 52% in controls. Local delivery of t-PA effectively reduced the thrombus size (P < 0.01 vs control). After systemic intravenous delivery of low-dose t-PA, no reduction of residual thrombotic stenosis, was observed. Reduction of residual thrombotic stenosis after intravenous delivery of high-dose t-PA, was similar to that achieved by local delivery of the drug. Angioscopy demonstrated a similar trend. High-dose drug delivery reduced systemic coagulability. Local delivery of an antithrombotic drug, using a double-occlusion balloon catheter, effectively prevented thrombus formation, and local delivery of t-PA induced thrombolysis without exerting a significant influence on coagulability.

Percutaneous cardioscopy of the left ventricle in patients with myocarditis

The morphology and function of the cardiac chambers have been evaluated clinically using cineventriculography, computed tomography, magnetic resonance imaging, and endomyocardial biopsy. Excluding the invasive technique of biopsy where tissue is actually removed, these other non-invasive techniques reveal only indirect evidence of endocardial and subendocardial pathology and, therefore, allow the potential for misdiagnosis from insufficient data. Fiberoptic examinations, as recently demonstrated in coronary, pulmonary, and peripheral vessels, allow direct observation of pathology otherwise unobtainable. Recently, similar techniques have been applied to examine the cardiac chambers of dogs and the right heart of humans. In this study, we examine the feasibility and safety of percutaneous fiberoptic cardioscopy of the left ventricle in patients with myocarditis.

Angioscopic Evaluation of Thrombi in the Culprit Coronary Lesions in Patients With Acute Myocardial Infarction

The purpose of this study was to evaluate intracoronary thrombi in the culprit lesions in patients with acute myocardial infarction (AMI) by angioscopy, and to compare them with clinical and angiographic features. We angioscopically observed the culprit coronary lesions in 66 patients with AMI (55 males and 11 females, 63.9±15.4 years old) just before interventional therapy. Thrombi were observed in 42 of 66 lesions (64%), namely, red thrombi in 16, mixed thrombi in 15, white thrombi in 11. In patients with complete obstruction (TIMI grade 0 and I), red thrombi were more frequently observed than mixed or white thrombi. On the other hand, in patients with incomplete obstruction (TIMI grade II and III), white thrombi were more frequently observed than the others. Angiographically, haziness and filling defect were significantly more frequently observed in patients with red thrombi than the others (p<0.05). The distance from proximal side branch to thrombi tended to be longer in patients with red thrombi than the others. The time from onset of AMI tended to be longer in patients with white thrombi than the others. These results suggest that blood flow may be an important determinant of thrombi characterization.

Dye-Staining Coronary Angioscopy and Cardioscopy

Coronary angioscopy or cardioscopy using biocompatible markers is one choice for evaluation of tissues, cells, or molecules which comprise the target lesions. Angioscopy using EB as a biomarker, namely, dye-staining angioscopy, has been developed and applied for molecular imaging of the substances that constitute atherosclerotic lesions.