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// Tomohiro Yasuda 1,2,3 , Kazuya Fukumura 1 , Takanobu Tomaru 3 and Toshiaki Nakajima 1,4 1 Graduate School of Medicine, University of Tokyo, Tokyo, Japan 2 School of Nursing, Seirei Christopher University, Shizuoka, Japan 3 Faculty of Medicine, Toho University, Chiba, Japan 4 Heart Center, Dokkyo Medical University Hospital, Tochigi, Japan Correspondence to: Tomohiro Yasuda, email: // Keywords : sarcopenia, vascular occlusion, muscle hypertrophy, resistance exercise, arterial stiffness, Gerotarget Received : December 08, 2015 Accepted : May 12, 2016 Published : May 23, 2016 Abstract We examined the effect of elastic band training with blood flow restriction (BFR) on thigh muscle size and vascular function in older women. Older women were divided into three groups: low-intensity elastic band BFR training (BFR-Tr, n = 10), middle- to high-intensity elastic band training (MH-Tr, n = 10), and no training (Ctrl, n = 10) groups. BFR-Tr and MH-Tr groups performed squat and knee extension exercises using elastic band, 2 days/week for 12 weeks. During BFR-Tr exercise session, subjects wore pressure cuffs around the most proximal region of both thighs. The following measurements were taken before (pre) and 3-5 days after (post) the final training session: MRI-measured muscle cross-sectional area (CSA) at mid-thigh, maximum voluntary isometric contraction (MVIC) of knee extension, central systolic blood pressure (c-SBP), central-augmentation index (c-AIx), cardio-ankle vascular index testing (CAVI), ankle-brachial pressure index (ABI). Quadriceps muscle CSA (6.9%) and knee extension MVIC (13.7%) were increased ( p < 0.05) in the BFR-Tr group, but not in the MH-Tr and the Ctrl groups. Regarding c-SBP, c-AIx, CAVI and ABI, there were no changes between pre- and post- results among the three groups. Elastic band BFR training increases thigh muscle CSA as well as maximal muscle strength, but does not decrease vascular function in older women.

AIM We investigated whether cardio-ankle vascular index (CAVI), an arterial stiffness marker, independently predicts future cardiovascular events in subjects with metabolic disorders. METHODS 1562 outpatients underwent CAVI between April 2004 and March 2006 at Toho University, Sakura Medical Center in Chiba, Japan. Patients who already had cardiovascular events at baseline, patients with low ankle brachial index (＜0.9), and patients with atrial fibrillation were excluded. After exclusion, 1080 subjects with metabolic disorders including diabetes mellitus, hypertension and dyslipidemia were screened and followed prospectively. RESULTS Eventually, 1003 subjects (92.9% of 1,080 subjects) followed until March 2012 (follow-up duration 6.7±1.6 years) were analyzed. During the observation period, 90 subjects had new-onset myocardial infarction or angina pectoris confirmed by angiography. All subjects were stratified into quartiles by baseline CAVI (Q1: CAVI ≤8.27, Q2: CAVI 8.28-9.19, Q3: CAVI 9.20-10.08, Q4: CAVI ≥10.09). Age, male ratio and future cardiovascular events increased as CAVI quartile became higher. In Cox proportional hazards regression analysis, the factors independently associated with higher risk of future cardiovascular events were every 1.0 increment of CAVI [hazard ratio (HR) 1.126, p= 0.039], male gender (HR 2.276, p=0.001), smoking (HR 1.846, p=0.007), diabetes mellitus (HR 1.702,p=0.020), and hypertension (HR 1.682, p=0.023). CONCLUSION In individuals with metabolic disorders, CAVI was a predictor of future cardiovascular events, independent of traditional coronary risk factors. CAVI is a potentially valuable tool to identify persons likely to benefit from more intensive therapeutic approaches.

Objective To investigate the relationship between Parkinson's disease (PD) and the cardio-ankle vascular stiffness index (CAVI), a novel non-invasive measurement of vascular stiffness. Methods A total of 63 PD subjects who underwent CAVI measurement were enrolled, including 30 men and 33 women 69.1±7.5 years of age (range: 46-79 years). Sixty-three non-PD subjects (30 men, 33 women, mean age: 68.7±7.6 years [range: 43-79 years]) served as controls. Comparisons between the control and PD subjects were made using Fisher's protected least significant difference, the Bonferroni-Dunn test, Scheffe's test and the unpaired t-test. Results 1) The average CAVI values were as follows: control, 9.3±0.9; PD, 9.0±1.0 (p=0.049). The differences in the CAVI values between the groups and the index values (normative data provided internally in the VaSera system) were as follows: control, 0.4±0.8; PD, 0.03±0.9 (p=0.011). The CAVI values of the PD patients were significantly smaller than those of the control subjects. 2) Among the control subjects, the CAVI values in the subjects with atherosclerotic risk factors (hypertension, dyslipidemia and/or diabetes) were significantly higher than those observed in the subjects without risk factors. In contrast, among the PD patients, the CAVI values in the subjects with atherosclerotic risk factors were equivalent to those observed in the subjects without risk factors. 3) Among the PD patients, the CAVI values did not change with the motor stage. Conclusion The results of the present study show that, compared with control subjects, PD patients exhibit normal CAVI values despite having mild but significant atherosclerotic risk factors, e.g., hypertension and diabetes. These findings suggest that PD patients are less vulnerable to systemic atherosclerosis than their risk factors may suggest.

The cardio-ankle vascular index (CAVI) has been proposed as a new noninvasive marker of arterial stiffness independent of blood pressure. Arterial stiffness is closely related to afterload, and elevated afterload aggravates heart failure. We hypothesized that CAVI is a potential marker of afterload in patients with heart failure. Thirty patients who were admitted because of acute heart failure were identified retrospectively from a review of clinical records. Plasma brain natriuretic peptide (BNP) levels, CAVI, cardiothoracic ratio (CTR), and echocardiographic parameters obtained during acute and chronic phases of heart failure were analyzed. Left ventricular ejection fraction (LVEF) increased significantly and CTR, BNP and CAVI decreased significantly after treatment of heart failure. A significant negative correlation was observed between the change in CAVI and change in LVEF in all subjects (r = -0.3272, P < 0.05). To examine the relationship between CAVI and LVEF, we divided the patients into two subgroups (∆CAVI < -0.5; CAVI decrease group, ∆CAVI ≥ -0.5; CAVI non-decrease group). CAVI was significantly improved after heart failure treatment only in the CAVI decrease group. LVEF decreased significantly in both groups, but the P value was smaller in the CAVI decrease group than in the CAVI non-decrease group. The change in LVEF correlated significantly with the change in CAVI in the CAVI decrease group (r = -0.4201, P < 0.05), whereas no significant correlation was found in the CAVI non-decrease group. CAVI correlates inversely with LVEF after heart failure treatment. Our results suggest that CAVI might partially reflect the afterload in patients with heart failure.

Background The distribution of frequency power (DFP) within the QRS complex (QRS) is unclear. This study aimed to investigate the DFP within the QRS in ischemic cardiomyopathy (ICM) with lethal ventricular arrhythmias (L-VA). A computer simulation was performed to explore the mechanism of abnormal frequency power. Methods The study included 31 ICM patients with and without L-VA (n = 10 and 21, respectively). We applied the continuous wavelet transform to measure the time-frequency power within the QRS. Integrated time-frequency power (ITFP) was measured within the frequency range of 5–300 Hz. The simulation model consisted of two-dimensional myocardial tissues intermingled with fibroblasts. We examined the relation between frequency power calculated from the simulated QRS and the fibroblast-to-myocyte ratio (r) of the model. Results The frequency powers significantly increased from 180 to 300 Hz and from 5 to 15 Hz, and also decreased from 45 to 80 Hz in patients with ICM and L-VA compared with the normal individuals. They increased from 110 Hz to 250 Hz in ICM alone. In the simulation, the high-frequency power increased when the ratio (r) were 2.0–2.5. Functional reentry was initiated if the ratio (r) increased to 2.0. Conclusions Abnormal higher-frequency power (180–300 Hz) may provide arrhythmogenic signals in ICM with L-VA that may be associated with the fibrous tissue proliferation.

Background: Cholesterol (C) and cholesteryl esters (CE) within coronary plaques are minimally visualized directly by any of the available imaging modalities in vivo. If they are rendered visible in vivo, the progression of coronary plaques and the effects of respective therapies on these plaques can be objectively evaluated. Hypothesis: The C and CE within human coronary plaques can be visualized by near-infrared fluorescence angioscopy (NIRFA). Methods: By exciting at 710 ± 25 nm and emitting at 780 nm, near-infrared fluorescence (NIRF) of lipid components was examined by microscopy in vitro. Lipid components in 49 plaques of 32 excised human coronary arteries were examined by NIRFA in vitro. Coronary plaques were examined by NIRFA in 25 patients with coronary artery disease. Results: C, CE, and calcium (Ca) individually did not exhibit NIRF but did in the presence of β-carotene, which is known to coexist with lipids in the vascular wall. Other substances that are contained in atherosclerotic plaques did not.2 The excised human coronary plaques were classified as those with NIRF and those without. The former plaques were classified into homogenous, doughnut-shaped, and spotty types. Histological examinations revealed that these image patterns were determined by the differences in the locations of C, CE, and Ca, and that those deposited within 700 μm in depth from the plaque surface were imaged by NIRFA. Homogenous, doughnut-shaped, or spotty NIRFA images were also observed in patients. Conclusions: NIRFA is feasible for 2-dimensional imaging of C and CE deposited in human coronary plaques. Copyright © 2010 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

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. (J Interven Cardiol 2010;23:470–478)

Objectives This study was carried out to detect vulnerable coronary plaques by color fluorescent angioscopy. Background Collagen fibers (CFs) mainly provide mechanical support to coronary plaques. Oxidized low-density lipoprotein (Ox-LDL) induces macrophage proliferation, which in turn destroy CFs while accumulating lipids. As such, demonstration of the absence of CFs, deposition of lipids, and the Ox-LDL may suggest plaque instability. Methods Fluorescence of the major components of the atherosclerotic plaques was examined by fluorescent microscopy using a 345-nm band-pass filter and 420-nm band-absorption filter (A-imaging). Fluorescence of Ox-LDL was examined using a 470-nm band-pass filter and 515-nm band-absorption filter (B-imaging) and Evans blue dye as an indicator. Fluorescence in 57 excised human coronary plaques was examined by A-imaging color fluorescent angioscopy. Oxidized LDL in 31 excised coronary plaques and in 12 plaques of 7 patients was investigated by B-imaging color fluorescent angioscopy. Results Collagen I, collagen IV, and calcium exhibited blue, light blue, and white autofluorescence, respectively. In the presence of beta-carotene which coexists with lipids in the vascular wall, collagen I and IV exhibited green, collagen III and V white, cholesterol yellow, cholesteryl esters orange fluorescence. Oxidized LDL exhibited reddish brown fluorescence in the presence of Evans blue dye. Therefore, coronary plaques exhibited blue, green, white-to-light blue, or yellow-to-orange fluorescence based on plaque composition. Histological examination revealed abundant CFs without lipids in blue plaques; CFs and lipids in green plaques; meager CFs and abundant lipids in white-to-light blue plaques; and the absence of CFs and deposition of lipids, calcium, and macrophage foam cells in the thin fibrous cap in yellow-to-orange plaques, indicating that the yellow-to-orange plaques were most vulnerable. Reddish brown fluorescence characteristic of Ox-LDL was observed in excised coronary plaques, as also in patients. Conclusions Color fluorescent angioscopy provides objective information related to coronary plaque composition and may help identify unstable plaques.

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.

Objectives: Pelvic autonomic dysfunction without tetraparesis can be a sequel of acute longitudinal myelitis. Methods: A 25-year-old woman had suffered from pelvic dysfunction (urinary retention and severe constipation) without tetraparesis for 5 months as a sequel of rubella-related acute longitudinal myelitis at the spinal segments of C2 to T9. She still had brisk deep tendon reflexes and extensor plantar responses. We performed autonomic function tests in the patient. Results: Pelvic autonomic function tests revealed acontractile detrusor and unrelaxing sphincter, suggesting the shock phase of a suprasacral spinal cord lesion; as well as loss of voluntary sphincter contraction, prolonged colonic transit time, decreased spontaneous phasic contractions, and paradoxical sphincter contraction on defecation, suggesting a suprasacral cord lesion. Conclusion: These findings indicated that the lateral medullary reticulospinal tracts just inside the pyramidal tract, for example, the descending pathways to the bladder and bowel, and the adjacent corticospinal tract to the sphincter, were selectively affected in our case.

The cerebellum is one of the regions that contribute to urinary dysfunction in humans. A 43-year-old woman at age 35 had an acute onset of encephalitis that led to fever, generalized convulsion and coma. Six months after the disease onset, she regained consciousness and developed generalized myoclonus, cerebellar ataxia and overactive bladder, e.g., urinary urgency, daytime urinary frequency, and urinary incontinence. Eight years after the disease onset, she was revealed to have cerebellar atrophy on MRI, cerebellar hypoperfusion on SPECT, and detrusor overactivity on urodynamic study. Selective inflammation in the cerebellum seemed to produce cerebellar ataxia and overactive bladder in our case.

経胸壁ドプラ心エコー法による冠動脈の描出が可能となり，冠血流速波形の解析から冠循環の評価が行われるようになってきた．冠動脈遠位部は検出率が高く，その血流評価に対する多数の報告がなされているのに対して，冠動脈近位部を評価した報告は少ない．今回我々は，経胸壁ドプラ心エコー法により，冠動脈近位部狭窄の診断が可能であった不安定狭心症の2症例を経験したので報告する．症例1：79歳，男性．胸痛を主訴に入院．発作時の心電図では II ，III，aVF，V3‐6のST低下を認めた．経胸壁心エコー検査では，左室壁運動が心尖部で若干低下していたが左室駆出率は正常であった．大動脈弁レベルの短軸像で冠動脈近位部を直接描出したところ，左前下行枝近位部に加速血流を認め拡張期最高血流速度は104cm/秒と高速であった．冠動脈造影の結果，分節6に99%狭窄を認め，経胸壁心エコー検査で認められた狭窄部と一致していた．狭窄部にステントを留置し良好な拡張に成功した．術後の経胸壁心エコー検査では，冠動脈内の加速血流は消失し拡張期最高血流速度は40cm/秒と正常化した．症例2：59歳，男性．胸痛を主訴に入院．発作時の心電図で II ，III，aVFの陰性T波を認めた．経胸壁心エコー検査では，左室壁運動異常は認めなかった．大動脈弁レベルの短軸像で冠動脈近位部を直接描出したところ，右冠動脈近位部に加速血流を認め拡張期最高血流速度は108cm/秒と高速血流であった．冠動脈造影の結果，分節1に99%狭窄を認め，経胸壁心エコー検査で認められた狭窄部と一致していた．狭窄部にステントを留置し良好な拡張に成功した．術後の経胸壁心エコー検査では，冠動脈内の加速血流は消失し拡張期最高血流速度は26cm/秒と正常化した．非ST上昇型の不安定狭心症において，経胸壁ドプラ心エコー法により冠動脈近位部の狭窄病変を直接描出することが可能であった．本法は，冠動脈近位部狭窄の有無を心臓カテーテル検査前に予測する上で有用な検査法と考えられた．

大動脈四尖弁は大動脈二尖弁と同様に大動脈弁機能不全の原因疾患となる先天性弁膜症である. 発生頻度は大動脈二尖弁より少なく稀な疾患である. 今回, 超音波検査により術前に大動脈弁四尖弁と診断し得た2症例を経験したので報告する. 症例1 : 63歳, 男性, ペースメーカー植込み術を受けている. 労作時呼吸困難を自覚するようになり入院した. 心エコー検査の結果, 重度の大動脈弁逆流を認め, 左冠尖と無冠尖の間に副尖を有する大動脈四尖弁であった. 手術で四尖が確認され大動脈弁置換術 (SJM 23 mm) を施行した. 組織像では軽度の線維増生と粘液変性が認められた. 症例2 : 58歳, 女性, 高血圧と気管支喘息のため近医で加療を受けていた. 労作時呼吸困難を自覚するようになり入院した. 心エコー検査の結果, 重度の大動脈弁逆流と大動脈弁狭窄の所見を認めたが, 大動脈弁形態は不明であった. 経食道心エコー検査を施行し, 左冠尖と右冠尖の間に副尖を有する大動脈四尖弁と判明した. 手術で四尖が確認され大動脈弁置換術 (SJM 17 mm) を施行した. 組織像では高度の線維増生と石灰化が認められた. 心エコー検査で大動脈弁膜症の原因を検索する際には大動脈四尖弁の可能性も考慮に入れ慎重に観察する必要がある.

The mechanism of the antithrombotic effects of heparin and the synthetic antithrombin agent argatroban was evaluated in a dog model. Thrombus formation following balloon injury was evaluated by angioscopy in the right iliac arteries of 20 dogs to serve as a control. After the evaluation of the growth of thrombus on the control side, heparin (200 U/kg) or argatroban (0.2 mg/kg) was infused intravenously, and the distal site of the contralateral left iliac artery was injured in the same manner. At 30 to 120 min before the final examination, the proximal site of the left iliac artery also was injured. After antithrombotic drug infusion, the percent angioscopic stenosis at the distal site was much lower (P0.0001) than that of the control site (mean stenosis index: 0.67 in heparin vs. 3.8 in control, and 0.25 in argatroban vs. 4.3 in control); however, thrombus formation was observed at the proximal site. With local delivery of a low dose of either antithrombotic drug (n=10), an antithrombotic effect was maintained until 4 h after the infusion. A very weak fluorescence of FITC-heparin was detected at the injured artery 2 h after infusion. In a shunt experiment involving 5 dogs, carotid arteries were injured and incubated in oxygenated Krebs--Henseleit solution before auto grafting into the femoral artery. At 2 h after the grafting, no thrombus was formed in the grafted vessels incubated for 4 h, but was formed in those incubated for 10 min. These results indicate that the relatively long antithrombotic effect of these drugs may be due to a local drug effect at the injured artery, as well as the recovery of the anti-thrombogenicity of the injured artery.

Aim To evaluate progression of arteriosclerosis using cardio-ankle vascular index(CAVI) and carotid duplex ultrasonography(DUS) in young and adolescent patients considered to be at risk of cardiovascular disease. Methods We evaluated the progression of arteriosclerosis using CAVI and carotid DUS in 240 young and adolescent patients. Dyslipidemia(DL), hypertension(HT), and diabetes mellitus(DM) were major cardiovascular risk factors. Patients were divided to 4 groups according to number of risk factors. Results In terms of risk factors, CAVI and CAVI difference(CAVI-D) were elevated only in the HT group(p=0.0290, p=0.0243 vs. no risk respectively). CAVI-D was positively associated with diastolic blood pressure(DBP). Mean IMT was positively associated with LDL-C or systolic blood pressure, and negatively with HDL-C. Plaque score was associated with LDL-C or DBP. In patients with the 3 risk factors, CAVI, CAVI-D and mean intima-media thickness(IMT) were significantly higher than in those without risk(p=0.0009, p=0.0042 and p=0.0151 respectively), and CAVI and CAVID were higher than in those with 1 risk(p=0.0204 and p=0.0231). Carotid plaque develops from around 30 years of age in Japan. Despite numbers of risk factors, there were no differences in CAVI, CAVI-D, mean IMT or plaque score between smoker and non-smoker groups. Conclusion In conclusion, an increase in the number of risk factors also results in progression of arteriosclerosis in young and adolescent patients. HT was the most important risk factor for arteriosclerosis in these patients.

A model to assess thrombus formation following vascular injury was evaluated using various interventional systems. The model consisted of a 'stretchable' shunt box that served as an arteriovenous shunt between the carotid artery and jugular vein in dogs. Arterial homografts obtained from both carotid and femoral arteries were mounted between two plastic connectors attached to either side of the shunt box. The opposing walls of the shunt box were then stretched apart to achieve the original length of the arteries. The arterial side of the box was connected to the ipsilateral carotid artery and the venous side was connected to the contralateral jugular vein. Haemostasis valves were placed at the exit ports on the venous side of the shunt box. These were used as an access to the various interventional catheters into the lumens of the homografts. Interventions were performed prior to initiating blood flow. After the interventions, 111indium-labelled platelets were injected on the arterial side of the shunt box and arterial blood flow initiated across the shunt. After one hour of circulation through the shunt box, the blood flow was interrupted, and the homografts were perfusion-fixed with glutaraldehyde and segments removed for radioactive counts and processed for histology. This shunt box was then used to compare platelet adhesion and thrombus formation after balloon angioplasty (BA) to direct laser (LA) and laser-thermal angioplasty (LTA). A total of 28 arteries were used from seven dogs. In each experiment, one homograft was used as control, and three other homografts were treated with either BA, LA or LTA. Following the interventions, 111indium-labelled platelets were injected and circulated for one hour using the dog's native circulation. Labelled platelet counts for BA (19102+/-4869/cm2; mean +/- SE) were significantly greater than LA (7038+/-980/cm2), thermal LTA (5189+/-1961/cm2), and control (1575+/-541/cm2), respectively (p0.05, ANOVA). Histology examination showed few platelets at LA, LTA and control sites whereas extensive platelet adhesion was noted at BA treated sites. The model provided a means to conduct simultaneous comparison of several interventions under similar conditions. In this case thermal treatment of the arterial homografts had the least amount of platelet adhesion.

Acute reocclusion after successful angioplasty is a severe complication. The preventive effects of heparin, the synthetic antithrombin, argtroban, and the defibrinogenating agent batroxobin on reocclusion after balloon angioplasty of thrombotic occlusions were evaluated in canine iliac arteries. After the 2-hour-old thrombus was evaluated by angiography and angioscopy, percutaneous transcatheter angioplasty (PTA) was performed on the thrombotic stenosis. We used one of the three agents, heparin (100 U/kg), the antithrombin argatroban (0.3 mg/kg), or the defibrinogenating agent batroxobin (0.3 U/kg). Then angioscopy and angiography were performed before, just after, and 2 hours after PTA. After PTA, angiography revealed a marked reduction in percent stenosis in all groups (from 88 ± 8% to 24 ± 4% in the heparin group, from 79 ± 7% to 26 + 11% in the argatroban group and from 89 ± 12% to 32 ± 7% in the batroxobin group). At 2 hours after PTA, angiography demonstrated a greater reduction in percent stenosis with argatroban (from 26 ± 11% to 9 ± 3%) and batroxobin (from 32 ± 7% to 10 ± 8%), and maintenance of percent stenosis reduced by PTA with heparin (from 24 ± 5% to 28 ± 9%) when compared with the significant reversal of percent obstruction in the control side. Angioscopic visualization also demonstrated a similar trend. These results show that these antithrombotic drugs have a preventive effect on reocclusion after balloon angioplasty for thrombotic obstruction.

Since the treatment of thrombotic disease by antithrombotic drugs may be associated with bleeding complications, a local delivery technique for administration of the drug may be useful. The efficacy of low-dose local delivery of an antithrombotic drug on thrombosis was investigated in 73 dogs. The antithrombotic drug (heparin, 25U/kg, antithrombin: argatroban, 0.05mg/kg, or defibrinogenating agent: batroxobin, 0.05U/kg) was infused locally to a 1-h-old thrombus, and no drug was given in controls. The effect of the local delivery on the thrombus was evaluated. Low- and high-dose systemic drug delivery was also evaluated. The mean reduction in thrombotic coronary stenosis observed by angiography was 30.3% with argatroban, 22% with heparin, and 20.8% with batroxobin (P < 0.005 vs controls). Systemic delivery of low-dose heparin or argatroban did not induce any change in thrombus size. With high-dose systemic drug delivery (heparin 250 U/kg, argatroban 0.5 mg/kg), the mean reduction of thrombotic stenosis was 15.2% with heparin and 32.8% with argatroban (P < 0.005 vs controls). In iliac arterial thrombosis, after local delivery of the drugs, the mean reduction of thrombotic stenosis observed by angiography was 24.4% in the argatroban group, and 19.2% in the heparin group (P < 0.05 vs controls, respectively). With high-dose systemic heparin delivery, the mean reduction of the thrombotic stenosis was 13.2% (P < 0.01 vs control). Angioscopy also demonstrated a similar trend. The high-dose drug delivery reduced systemic coagulability. Thus, local delivery of an antithrombotic agent can reduce the thrombus size in the coronary and iliac arteries without having any significant influence on coagulability.

To examine whether angiogenesis and myocardial salvage occur, 30 micrograms basic fibroblast growth factor (bFGF) and 3 mg heparin sulfate (HS) were injected through the right atrium into the pericardial cavity by a thin needle-tipped catheter in a canine model of acute myocardial infarction. One month later infarcted weight/left ventricle weight was 24% +/- 5.2%, 25% +/- 4.0%, 18% +/- 2.4%, and 10% +/- 1.8% (mean + SE) in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Vascular number in the infarcted area of the outer layer was 13 +/- 3.3, 20 +/- 2.2, 47 +/- 8.3, and 136 +/- 26.3/200 x 200 microns2 in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Thus the vascular number was the largest in the bFGF plus HS group. The vascular number was larger in the subepicardial than in the subendocardial infarcted areas. Vessels directed from the epicardium toward the subepicardial infarcted area were also observed. The transcatheter intrapericardial injection of bFGF plus HS caused angiogenesis and myocardial salvage. This method might bring about a selective therapeutic and preventive modality of myocardial infarction irrespective of coronary anatomy and contraindications for coronary interventions and surgery.

This study was designed to evaluate the efficacy of local versus systemic treatment of thrombosis with various antithrombotic drugs.Local use of low dose antithrombotic drugs has been proposed as being effective and safe.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.Sixty minutes after local treatment in 22 dogs, no thrombotic stenosis was observed by angiography in locally treated arteries (p0.005 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 was5% after high dose drug delivery (p0.05 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.Compared with systemic administration of antithrombotic drugs, local treatment is a safer and more effective method of preventing thrombosis.

It is not known whether the individual lesions that constitute tandem lesions of the coronary artery are developmentally or rheologically related. Luminal changes and their rheological significance were examined by percutaneous angioscopy in 44 tandem lesions of 21 patients with ischemic heart disease. Angioscopically, individual narrowing of angiographically documented tandem lesions appeared only as a tangentially expressed prominent portion of an atherosclerotic spiral fold. The directions of the fold were counterclockwise in the proximal to middle segments and clockwise in the distal segment of the right coronary artery, clockwise in the proximal to middle segments and counterclockwise in the distal segment of the left anterior descending artery, and counterclockwise in the proximal to middle segments of the left circumflex artery. The bloodstream always ran along the spiral folds in the tandem lesions. The results suggest that angiographically documented tandem coronary lesions are merely a tangential expression of atherosclerotic spiral folds and that they may act to prevent blood turbulence by generating a spiral laminal flow.

Ablation of the AV junction is an accepted technique for the management of selected supraventricular tachyarrhythmias. Radiofrequency ablation appears to be safe and effective for AV junction ablation in most patients, but the need for firm tissue contact may make it less effective for ventricular tachycardia and certain ectopic/atrial tachycardias. Laser energy can also be delivered through a catheter, and thus it may be an attractive alternative energy source for ablation. A new laser-electrode catheter was developed for modification of conduction through the AV node as a model for ablation of an arrhythmia substrate. A window for delivery of continuous-wave Nd:YAG laser energy was placed between the two electrodes of a bipolar electrode catheter. In vitro studies using a matrix of power versus time were performed to determine the energy that would create lesions of the appropriate size in vivo. Using this information, advanced AV block was successfully created in 16 of 17 dogs (94%) with the laser-electrode catheter. Advanced AV block was successfully created in all four dogs in the chronic study, and it persisted for 1-24 weeks of follow-up until sacrifice of the animals. Histologic examination demonstrated discrete thermal damage at the AV junction with no instances of septal perforation in the acute studies or progressive necrosis in chronically maintained dogs. Advanced AV block may be produced consistently and safely in dogs using a combined laser-electrode catheter.

We investigated the relationship between stroke and cardio-ankle vascular stiffness index (CAVI), a novel noninvasive measure of vascular stiffness.Eighty-five patients with cerebrovascular disease who underwent CAVI were enrolled in the current study. They were 63 men and 22 women with a mean age of 70.0 ± 10.8 years. They were divided into 4 groups according to neurologic abnormalities and magnetic resonance imaging (MRI) findings: 12 with transient ischemic attack (TIA), 26 with white matter ischemic lesions (WMLs), 17 with large artery atherosclerosis, and 30 with small vessel occlusion. Eight hundred fifty-four healthy patients (487 men and 367 women; mean age 65.1 ± 9.4 years) served as controls. The results were stratified by gender and age and statistically analyzed using the Fisher, Bonferroni-Dunn, and Scheffe tests.The average of CAVI was as follows: control males 60 to 69 years of age, 9.05 ± 0.82 (as a representative value); TIA, 9.3 ± 1.5; WML, 10.3 ± 1.3; large artery atherosclerosis, 10.2 ± 1.2; and small vessel occlusion, 10.0 ± 1.6, respectively. The difference in CAVI between each group and age- and gender-matched controls was 0.492 for TIA (no statistical significance); WML, 0.733 (P.001, and P = .002 Scheffe); large artery atherosclerosis, 0.838 (P.001, and P = .005 Scheffe); and small vessel occlusion, 1.034 (P.001), respectively. Linear regression analysis of CAVI and plaque score revealed a significant relationship in patients with ischemic cerebrovascular disease (P.05).Compared with healthy control subjects, CAVI is statistically greater in patients with ischemic cerebrovascular diseases, particularly with WML, large artery atherosclerosis, and small vessel occlusion, but not in patients with TIA. CAVI had a clear relationship with carotid ultrasound plaque score. It appears that CAVI is a simple and noninvasive test for indicating atherosclerosis in patients with stroke.

Direct argon or thermal laser angioplasty (LA) was evaluated for thrombogenicity using angioscopy, and compared with balloon angioplasty (BA). In each of 8 dogs, 4 segments (both proximal and distal iliac arteries) were treated by laser-thermal and/or balloon angioplasty. One segment was treated by balloon angioplasty and 3 other segments were treated with either thermal LA with 7 W using a "Hot-Tip" laser probe (2.0 mm), or BA and thermal LA, or a special optical probe which emits a 3 W argon laser beam. Mean percent area stenosis by thrombus was 44 +/- 23 in balloon-dilated, 23 +/- 21 in thermally-treated and balloon-dilated, 3 +/- 3 in thermally-treated, and 1 +/- 4 in directly-lased segments at 30 min. It was 62 +/- 28 in balloon dilated, 31 +/- 29 in thermally-treated and balloon-dilated, 5 +/- 6 in thermally-treated, and 1 +/- 2 in directly-lased segments at 60 min. Balloon-inflated segments had the highest percent area stenosis which was significantly higher than that of either the direct laser or thermally-treated segments (p < 0.0005). Histology showed thermal necrosis in laser-treated sites, and wall tears in BA sites. Thus, LA can provide a less thrombogenic arterial surface than BA.

Vasoreactivity of laser-treated vessels was investigated in two different experimental conditions. The canine left circumflex coronary artery (LCx) was lased under perfusion with Krebs-bicarbonate buffer by means of a thermal laser (hot-tip probe, HT) at 7 W for 6 seconds and an argon laser beam through a 300 microns optical fiber at 3 W (tip power) for 1 second at 12 spots. A nontreated segment of the LCx served as a control. Two 3-mm long segments were obtained from the treated segment: one to measure the results of potassium (K) induced contraction, and another 3, 4 diaminopyridine (DAP; K channel inhibitor) induced contraction. In 11 instances, coronary angiography of the perfused artery showed less than 50% stenosis after laser treatment. The segments were then mounted isometrically with 1 g tension in Krebs-bicarbonate buffer. Contraction was induced either with 30 mM KCI or 10(-2) M DAP and expressed as developed tension (gram; g). KCI induced vasocontraction of 4.15 +/- 0.93 g in the control, 0.33 +/- 0.71 g in laser irradiated segments (P < 0.0001 vs control), and 0.02 +/- 0.06 g in thermally-treated segments (P < 0.0001 vs control). DAP induced vasocontraction of 5.21 +/- 1.32 g in the control, 0.39 +/- 0.83 g in laser irradiated segments (P < 0.0001 vs control), and 0.07 +/- 0.13 g in thermally treated segments (P < 0.001 vs control). In 4 instances, more than 50% stenosis remained and additional balloon dilatation reduced the stenosis to less than 50%. The lesions also showed reduced vasoreactivity. In vivo thermal angioplasty resulted in reduced vasoreactivity compared to control in 4 anesthetized dogs. Thus, laser and thermal angioplasty reduced vasoreactivity induced by either KCI or 3, 4 DAP. Neither acetylcholine at 10(-6) M nor papaverine at 10(-4) M was able to induce relaxation of treated segments. In conclusion, 1) the lased coronary artery loses its vasoreactivity to either a constrictive or relaxing agent, 2) although stenosis may be produced by laser energy, additional balloon dilatation can reduce residual stenosis, and 3) laser thermal or argon laser angioplasty may prevent severe coronary spasm.

Ablation efficacy of pulsed lasers on human arterial tissue and associated shock waves have been investigated by means of excimer laser at 308 nm, pulsed-dye laser at 480 nm, and holmium-YAG laser at 2.1 microns. A multifiber catheter was used for lasing at 420 mjoules/pulse with holmium-YAG, 18.9 mjoules/pulse with excimer, and 100 mjoules/pulse with pulsed-dye laser. Ablation efficiency (ablated volume/energy) was greatest with pulsed-dye laser in blood and excimer laser in saline solution. There was selectivity for atheroma with pulsed-dye laser (ablation efficiency in atheroma versus normal tissue, 58 versus 27 x 10(-2) mm3/joule in blood; p less than 0.005) and holmium-YAG laser (12.6 versus 5.6 x 10(-2) mm3/joule in blood; p less than 0.001). Ablation efficiency of pulsed-dye laser was enhanced by blood (0.58 in blood versus 0.17 mm3/joules in saline for atheroma; p less than 0.005). Shock waves were correlated with ablation efficiency (r = 0.63 and 0.74 for pulsed-dye laser and holmium-YAG laser, respectively). There was neither selectivity for atheroma nor influence of blood medium with excimer laser. Only holmium-YAG laser could ablate tissue at a distance from the target in the blood medium. Histologic findings showed that all lasers could create smooth-edged craters with minimal coagulation necrosis. In conclusion, laser irradiation with holmium-YAG and pulsed-dye lasers could selectively ablate atheromatous tissue with minimal thermal injury, whereas excimer laser could not. Ablation efficiency was correlated with shock waves. Efficiency of pulsed-dye laser was enhanced by blood.

Shock waves were investigated using an excimer laser at 308 nm with 18.9 mjoules/pulse, a pulsed dye laser at 480 nm with 100 mjoules/pulse, and a holmium YAG (yttrium-aluminum-garnet) laser at 2.1 microns with 420 mjoules/pulse. At a distance from the target tissue, excimer lasing resulted in no shock waves in saline, while the other lasers produced smaller shock waves than those recorded when the laser was in contact with tissue (0.22 versus 2.0 mm Hg with the pulsed dye laser, 0 versus 0.23 mm Hg with the excimer laser, and 0.44 versus 6.9 mm Hg with the holmium YAG laser; p less than 0.001, respectively). In blood, excimer laser irradiation at a distance from the tissue produced shock waves as great as those produced when the laser was in contact with the tissue (0.19 versus 0.24 mm Hg with the excimer laser, 1.8 versus 3.0 mm Hg with the pulsed dye laser, and 3.1 versus 5.9 mm Hg with the holmium YAG laser; p less than 0.001 with the pulsed dye and holmium YAG lasers, respectively). When lasing was done at 60 mjoules/mm2, the pulsed dye and excimer lasers produced similar shock waves when the lasers were in contact with tissue; however, the holmium YAG laser did not produce shock waves. Thus pulsed lasers can produce shock waves of different characteristics according to the laser source.

Aim: The aim of this study was to clarify the relationship between CAVI and serum cystatin C levels to understand the role of arterial stiffness in the presence of renal insufficiency.Methods: We enrolled 206 consecutive patients with cardiovascular risk factors and/or coronary artery disease (CAD) in the study. Serum cystatin C, estimated glomerular filtration rate (eGFR), and plasma levels of von Willebrand factor (vWF) and plasminogen activator inhibitor (PAI-1) were measured. CAVI was determined as an index of arterial stiffness.Results: For all patients, the mean serum cystatin C level was 0.81±0.21 mg/L and mean eGFR was 65.8±15.5 mL/min per 1.73 m2. In univariate analysis, CAVI levels significantly correlated with cystatin C levels (r=0.414, p

BACKGROUND Few data are available on the long-term outcome of patients who undergo laser-assisted balloon angioplasty for recanalization of occluded peripheral arteries. Because the cost of laser angioplasty is high, the value of the method should be carefully analyzed before it can be considered a routine method for recanalization. The purpose of this study was to evaluate the early and late results of laser-assisted balloon angioplasty in patients who could not be recanalized by conventional techniques. METHODS AND RESULTS Laser angioplasty was performed in 66 patients with total occlusion of the iliofemoral artery in whom mechanical techniques failed to recanalize the obstructed vessel. The system consisted of a pulsed dye laser operated at 480 nm, 2 microseconds/pulse, 5 Hz, 50 mJ/pulse coupled into a 0.021-in. laser catheter. The treatment laser was connected with a diagnostic laser to induce tissue fluorescence for spectroscopic analysis via the same fiber. The treatment laser was emitted only when atheromatous tissue was recognized. After a pilot hole was created by laser emission, dilatation was performed to enlarge the channel. The mean length of occlusion was 8.8 +/- 6.1 cm. The primary success rate was 82%. It did not depend on the length of occlusion but was greater in non-calcified than in calcified lesions (88% versus 71%, p less than 0.03). Complications included seven early reocclusions that could be recanalized and eight perforations without clinical sequelae. At a mean 18-month follow-up, 64% of the laser-treated arteries remained patent. The rate of patency was related neither to the length of the occlusion nor to calcifications but was lower in patients who had early reocclusion (p less than 0.02). CONCLUSIONS Pulsed dye laser-assisted balloon angioplasty is effective for recanalization of totally occluded arteries that cannot be treated by conventional means. The efficacy is limited by calcifications. The long-term patency rate is acceptable given the severity of the lesions.

Background Recently, arterial stiffness parameter called cardio-ankle vascular index (CAVI) has been developed. In the current study, using coronary angiographic (CAG) findings, the usefulness of CAVI as a marker of the severity of coronary atherosclerosis was compared with that of carotid atherosclerosis parameters obtained from high-resolution B-mode ultrasonography. Method and Result A total of 109 participants who underwent CAG were enrolled in the current study. They were divided into 4 groups according to the number of stenotic vessels on CAG; no lesion (0VD), 1-vessel (1VD), 2-vessel (2VD) and 3-vessel (3VD) groups. CAVI was significantly higher in 1VD group compared with the 0VD group (p

HMG-CoA reductase inhibitors (statins) have recently been reported to improve cardiac function, and decrease the incidence of heart failure (HF) in hyperlipidemic patients. However, evidence for statin treatment in patients with HF remains a subject of debate. Thus, a study was initiated to examine the effects of pitavastatin on cardiac function evaluated by echocardiographic findings and plasma brain natriuretic peptide (BNP) levels in patients with HF. Twenty-three patients with HF were treated with pitavastatin 1-2 mg/day in addition to standard therapy for 7.5 +/- 3.8 months. Left ventricular end-diastolic dimension (LVDd) and left ventricular end-systolic dimension (LVDs) were determined by echocardiography. Left ventricular ejection fraction (LVEF) was calculated using Teichholz's formula. Serum lipid and plasma BNP levels were also measured. During the follow-up period, LVEF was increased from 42 +/- 11 to 48 +/- 13% (P = 0.002). LVDs was reduced from 43 +/- 10 to 40 +/- 10 mm (P < 0.001), while there was no change in LVDd. E/A (n = 10) and deceleration time (n = 7), obtained in some patients, did not change significantly (0.89 +/- 0.33 to 0.77 +/- 0.17%, and 215 +/- 46 to 227 +/- 72 msec, respectively). In addition, the plasma BNP level was moderately, but significantly decreased from 94 +/- 78 to 70 +/- 56 pg/mL (P = 0.005). In subgroup analysis, LVEF was improved in both patients with ischemic and nonischemic HF. There was no significant correlation between the percent change in serum total cholesterol and the percent change in LVEF by pitavastatin treatment. Serum total cholesterol, LDL-cholesterol, and triglycerides decreased by 21%, 30%, and 15%, respectively, and HDL-cholesterol increased by 12%. Pitavastatin improved cardiac function in patients with HF, which generally worsens with time. The results suggest that pitavastatin may be beneficial for treatment of HF.

Background and Objective Exposure of the arterial wall matrix to blood leads to platelet deposition resulting in thrombosis. Because heat alters tissue matrix we proposed that heating reduces platelet deposition. Study Design/Materials and Methods Sixty arterial homografts (15 dogs) were mounted in an arterio-venous “shunt.” Interventions included balloon angioplasty (BA), direct laser (LA), laser-thermal (LTA), and combined LTABA. 111Indium-labeled platelets were circulated, radio activity measured, and homografts processed for histology. Results Radioactivity count (mean ± SE) at BA sites (13,853 ± 3,192 cpm/cm2) was greater than LA (7,038 ± 981), LTA (5,294 ± 1,145), LTABA (6,176 ± 1,571), and control (1,826 ± 339), P

The efficacy of local treatment of thrombosis with low-dose antithrombotic drugs (heparin: 30 U/kg, or argatroban: 0.02 mg/kg) was investigated using a novel porous balloon catheter. This novel balloon catheter can deliver drug into arterial walls without causing vascular trauma. Thrombus formation was significantly inhibited in balloon-injured and locally-treated iliac arteries compared with control balloon-injured arteries in 12 dogs. In the systemic high-dose delivery group (ten times as high as the low dose), thrombus formation in injured arteries was significantly less than that of controls in 7 dogs. Low-dose systemic delivery was not effective at inhibiting this thrombus formation. Thus, local treatment with an antithrombotic drug using this novel porous balloon catheter can prevent thrombosis without influencing systemic coagulability.

It is well known that the nonionic contrast media cmrently used are safer than ionic high-osmolar contrast media (1). However, contrast media-related cardiovascular adverse effects are still observed, especially in high-risk patients following their injection into left ventricle and coronary arteries (2,3). Iomeprol 400 (400 mgI/mL) (Iomeron; Bracco SpA, Milan, Italy; Eisai, Tokyo, Japan), which has been recentily developed, has some advantages such as 30-50 mg/mL higher iodine content and a lower osmolality of 750 mosm/kg • H20 than existing nonionic monomeric contrast media (4,5). Consequently, we can expect iomeprol 400 to have a better image and reduction of osmolality-related adverse effects such as patient discomfort and untoward hemodynamic and ECG changes. It is also noteworthy tha~ the use of iomeprol 400 is imperative and of clinical value, especially for the obese and broad-chested patients during cine cardioangiography. In this study, to determine the patient tolerance, safety, and usefulness of iomeprol 400 in cardioangiography, we compared the patient discomfort and hemodynamic and ECG effects of iomeprol 400 with those of iomeprol 350 (350 mgI/mL) during left ventriculography (LVG) and coronary angiography using a crossover design.

We investigated the ability of various antithrombotic drugs, delivered locally, to prevent restenosis after angioplasty in hypercholesterolemic rabbits. After dilating atherosclerotic iliac stenoses by balloon angioplasty, a low dose of heparin or a new antithrombotic drug, such as low molecular weight heparin (fragmin), argatroban, or batroxobin, was delivered locally using the balloon double-occlusion technique. In 1 group, high-dose heparin was administered intravenously. Animals that received no drugs served as a control group. After angioplasty, the stenotic segment was dilated and the mean percentage luminal stenosis fell from 89% to 9% in the group that received locally delivered heparin, from 88% to 7% in the group that received locally delivered argatroban, from 87% to 11% in the group that received locally delivered fragmin, from 88% to 15% in the group that received locally delivered batroxobin, from 82% to 18% in the group that received iv heparin (p

The 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.

The efficacy of local delivery of an antithrombotic drug on neointimal hyperplasia was investigated in 17 rabbits. One rabbit iliac artery was injured by a balloon catheter as a control injured artery. The other iliac artery was also injured and treated by local delivery of 25U/kg of heparin. One hour after the balloon injury, angioscopy demonstrated an occlusive or mural thrombus in all the controls, but few in the locally-treated arteries. Four weeks after balloon injury, the percent stenosis was 34±31% in the heparin treated group (n=7, p