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A myocardial perfusion reserve index in humans using first-pass contrast-enhanced magnetic resonance imaging

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第5期33卷 1386-1394页

作者： Cullen, JHS Horsfield, MA Reek, CR Cherryman, GR Barnett, DB Samani, NJ Univ Leicester Div Cardiol Dept Med & Therapeut Leicester LE1 7RH Leics England Univ Leicester Dept Clin Pharmacol Leicester LE1 7RH Leics England Univ Leicester Dept Med Phys Leicester LE1 7RH Leics England Univ Leicester Dept Radiol Leicester LE1 7RH Leics England

OBJECTIVES The purpose of this study was to evaluate a myocardial perfusion reserve index (MPRI) derived from a quantitative magnetic resonance imaging (MRI) technique in normal human volunteers and patients with coronary artery disease and to relate MPRI to coronary artery stenosis severity measured with quantitative arteriography. BACKGROUND Magnetic resonance imaging could be a useful noninvasive tool in the investigation of ischemic heart disease. However, there have been few studies in humans to quantify myocardial perfusion and myocardial perfusion reserve using MRT and none in patients with coronary disease. METHODS Twenty patients with angiographically proven coronary artery disease and five normal volunteers underwent both resting and stress (adenosine 140 mu g/kg(-1)/min(-1)) first-pass contrast-enhanced MRI examinations (using 0.05 nmol/kg(-1) of gadopentetate dimeglumine. Using a tracer kinetic model, the unidirectional transfer constant (K-i), a Perfusion marker for the myocardial uptake of contrast, was computed in each coronary arterial territory. The ratio of K-i for the rest and stress scans was used to calculate the MPRI. Percent reduction in lumina diameter of coronary lesions was measured using an automated edge-detection algorithm. RESULTS Myocardial perfusion reserve index was significantly reduced in patients compared with norma. subjects (2.02 +/- 0.7 vs. 4.21 +/- 1.16, p < 0.02). For regions supplied by individual vessels, there was a significant negative correlation of MPRI with percent diameter stenosis, (r = -0.81, p < 0.01). Importantly, regions supplied by vessels with;<40% diameter stenosis (non-flow limiting) had a significantly higher MPRI than regions supplied by stenoses of "intermediate" severity, that is, >40% to 59% diameter stenosis (2.80 +/- 0.77 and 1.93 +/- 0.38, respectively, p < 0.02). However, even regions supplied by vessels with <40% diameter stenosis had a significantly lower MPRI than volunteers (p < 0.01). CONCLUSION

关键词：腺苷/投药和剂量血流速度造影剂冠状血管造影术冠状动脉循环冠心病/诊断冠心病/病理生理学运动试验随访研究钆DTPA/投药和剂量输注静脉内磁共振成像心肌/病理学预后结果可重复性疾病严重程度指数血管舒张药/投药和剂量成年人女(雌)性人类男(雄)性中年人

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Relative bioavailability and effects of a high fat meal on single dose cilostazol pharmacokinetics

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CLINICAL PHARMACOKINETICS 1999年第2-Sup期37卷 13-23页

作者： Bramer, SL Forbes, WP Otsuka Amer Pharmaceut Inc Dept Clin Pharmacokinet Pharmacodynam & Metab Rockville MD 20850 USA

Objectives: The objectives of this research were to (1) assess the relative bioavailability following administration of a 100mg cilostazol suspension versus 100mg tablet;(2) assess dosage form equivalency (2 x 50mg compared with 1 x 100mg);(3) compare the relative bioavailability following a single 50mg dose of cilostazol administered as an ethanolic solution versus a 50mg tablet;and (4) determine the effects of high fat diet on the pharmacokinetics of cilostazol following a single dose of 100mg cilostazol in the fed or fasted state. Results were compiled from 3 separate studies to address these objectives. Design: All studies involved healthy adult males receiving single oral doses of cilostazol in the fed or fasted state. The fed state consisted of administering cilostazol after ingestion of a high fat meal. One study compared the relative bioavailability of 100mg suspension and 2 x 50mg tablet versus 100mg tablet in a randomised crossover design. The study involving administration of a 50mg cilostazol ethanolic solution was a single treatment study. The effects of food on the pharmacokinetics of cilostazol after administration of 100mg cilostazol in the fed or fasted state as well as the pharmacokinetic profile following administration of a single 50mg oral dose of cilostazol were assessed in a randomised crossover design. Study Participants: All participants were healthy nonsmoking males aged between 19 and 48 years whose bodyweight was within 15% of ideal bodyweight. Main Outcome Measures: Noncompartmental pharmacokinetic parameters: were determined for each study participant. Results: The area under the plasma concentration-time curve (AUC) parameters were within the 80 to 125% criterion for bioequivalence for the cilostazol and its primary metabolite, OPC-13015. The maximum observed plasma concentrations (C-max) for these formulations were not equivalent and indicated that the absorption of cilostazol from a suspension is more rapid than from a tablet. The ap

关键词：投药口服曲线下面积生物利用度交叉研究膳食脂肪类/药理学禁食/代谢悬液片剂四唑类/投药和剂量四唑类/血液四唑类/代谢四唑类/药代动力学血管舒张药/投药和剂量血管舒张药/血液血管舒张药/代谢血管舒张药/药代动力学成年人人类男(雄)性中年人

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The effect of withdrawal of drugs treating intermittent claudication

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AMERICAN JOURNAL OF SURGERY 1999年第2期178卷 141-146页

作者： Dawson, DL DeMaioribus, CA Hagino, RT Light, JT Bradley, DV Britt, KE Charles, BE Wilford Hall USAF Med Ctr Dept Gen Surg Surg Res Serv Lackland AFB TX 78236 USA

BACKGROUND: Pharmacologic treatment for intermittent claudication is a management option. This study evaluated the effect of withdrawal of drug therapies, cilostazol and pentoxifylline, on the walking ability of peripheral artery disease patients. METHODS: Single-blind placebo crossover from a randomized, double-blind trial;45 claudication patients received either cilostazol 100 mg orally twice daily (n = 16), pentoxifylline 400 mg orally three times daily (n = 13), or placebo (n = 16) for 24 weeks. After 24 weeks of double-blind therapy, treatment for all groups was placebo only, and follow-up continued through week 30. Treatment efficacy was established with treadmill testing. RESULTS: Profile analysis demonstrated a highly significant loss of treatment benefit after crossover (P = 0.001) for cilostazol-treated patients, but no significant change after crossover was observed with pentoxifylline. CONCLUSIONS: Drug withdrawal worsened the walking of claudicants who had benefited from cilostazol therapy. This decline with crossover to placebo suggests that the initial improvement with cilostazol treatment was due to the drug's action. Withdrawal of pentoxifylline did not adversely affect walking. Am J Surg. 1999;178: 141-146. (C) 1999 by Excerpta Medica, Inc.

关键词：投药口服交叉研究双盲法运动试验随访研究间歇性跛行/药物疗法间歇性跛行/病理生理学己酮可可碱/投药和剂量己酮可可碱/治疗应用安慰剂血小板聚集抑制剂/投药和剂量血小板聚集抑制剂/治疗应用单盲法四唑类/投药和剂量四唑类/治疗应用治疗结果血管舒张药/投药和剂量血管舒张药/治疗应用步行/生理学成年人老年人女(雌)性人类男(雄)性中年人

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Single-photon emission computed tomographic myocardial perfusion imaging in patients with mitral valve prolapse

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第4期85卷 516-518页

作者： Özkan, M Kaymaz, C Dinçkal, H Kirma, C Özdemir, N Akdemir, I Sönmez, K Mutlu, B Sansoy, V Önsel, Ç Kosuyolu Heart & Res Hosp Cardiol Clin TR-81020 Istanbul Turkey Istanbul Univ Cerrahpasa Med Fac Istanbul Turkey

Several studies have been undertaken using myocardial perfusion imaging to detect myocardial ischemia in patients with mitral valve prolapse (MVP).1–9 Controversial results were obtained in patients with MVP without coronary artery disease.1–11 Moreover, these previous studies have been performed mostly in the 1970s using planar myocardial perfusion imaging with thallium-201 (Tl-201).1–8 Recently, it was shown that single-photon emission computed tomography has better ability to allow visual analysis of all coronary regions in the diagnosis of coronary artery disease than planar imaging.12–14 This study was designed to assess myocardial perfusion imaging using single-photon emission computed tomographic (SPECT) analysis and recently established echocardiographic criteria for MVP.

关键词：胸痛/诊断胸痛/病因学诊断鉴别双嘧达莫/投药和剂量双嘧达莫/诊断应用超声心动描记术心电描记术运动试验注射静脉内二尖瓣脱垂/放射性核素显像二尖瓣脱垂/超声检查心肌缺血/诊断前瞻性研究放射性药物/投药和剂量放射性药物/诊断应用可重复性结果 99m锝甲氧基异丁基异腈/投药和剂量 99m锝甲氧基异丁基异腈/诊断应用体层摄影术发射型计算机单光子血管舒张药/投药和剂量血管舒张药/诊断应用成年人女(雌)性人类男(雄)性中年人

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Antiischemic effects of nicardipine and nitroglycerin after coronary artery bypass grafting

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ANNALS OF THORACIC SURGERY 1999年第2期67卷 417-422页

作者： Apostolidou, IA Despotis, GJ Hogue, CW Skubas, NJ McCawley, CA Hauptmann, EL Lappas, DG Washington Univ Sch Med Dept Anesthesiol Div Cardiothorac Anesthesia St Louis MO 63110 USA

Background. We assessed the efficacy of a continuous infusion of nicardipine and nitroglycerin in reducing the incidence and severity of perioperative myocardial ischemia during elective coronary artery bypass grafting procedures in a prospective, randomized, controlled study. Methods. Patients received either nicardipine infusion (0.7 to 1.4 mu *** (-1).min(-1);n = 30) or nitroglycerin (0.5 to 1 mu ***.(-l).min(-1);n = 30) or neither medication (n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes (MIE) were considered to have occurred with ST-segment depressions: or elevations of at least 1 mm and at least 2 mm (for both depressions or elevations), each at J + 60 ms and lasting at least 1 minute, using a two-channel Holter monitor. Results. Only nicardipine significantly decreased the duration (p = 0.02) of the l-mm or greater minutes per hour (3.2 + 1.2 minutes per hour) and eliminated the number (p = 0.02) of the 2-mm or greater minutes per hour (zero minutes per hour) when compared with control patients (17.2 +/-: 5.6 minutes per hour and 0.17 minutes per hour, respectively) during the intraoperative postbypass period. Conclusions. Our results suggest that nicardipine lessened the severity of myocardial ischemia shortly after coronary revascularization and could be considered as an alternative to standard antiischemic therapy. (C) 1999 by The Society of Thoracic Surgeons.

关键词：冠状动脉分流术冠心病/外科学剂量效应关系药物心电描记术便携式/药物作用输注静脉内心肌缺血/诊断心肌缺血/药物疗法尼卡地平/投药和剂量硝酸甘油/投药和剂量手术后并发症/诊断手术后并发症/药物疗法前瞻性研究治疗结果血管舒张药/投药和剂量老年人女(雌)性人类男(雄)性中年人

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Lupus carditis:: Evaluation with technetium-99m MIBI myocardial SPECT and heart rate variability

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ANGIOLOGY 1999年第2期50卷 143-148页

作者： Laganà, B Schillaci, O Tubani, L Gentile, R Danieli, R Coviello, R Baratta, L Scopinaro, F Univ Roma La Sapienza Dept Clin Med I-00185 Rome Italy Univ Roma La Sapienza Sez Med Nucl Dept Med Sperimentale & Patol Rome Italy

The objective of this paper was to investigate the incidence of myocardial perfusion defects in patients with systemic lupus erythematosus (SLE) associated with dysautonomic alterations. Twenty patients without any sign or symptoms of heart disease, selected from a larger population of patients with SLE, underwent technetium-99m sestamibi (Tc-99m MIBI) single photon emission computed tomography (SPECT), at rest and after dipyridamole infusion;they also underwent heart rate variability (HRV) examination by a 24 hour ambulatory electrocardiography, analyzing in the time domain the standard deviation of the R-R intervals average (SDNN) and the percentage of R-R adjacent intervals differing from each other more than 50 msec (pNN50);in the frequency domain the low (LF) and high frequencies (HF) were analyzed. Twenty healthy volunteers served as control group for heart rate variability. At MIBI-SPECT examination, the scan was found abnormal in 15 patients and normal in five: three patients demonstrated reversible defects in the anteroseptal region, four had irreversible defects in a region (two in the anteroseptal region and two in the lateral region), two had rest defects in two different regions (lateral and inferior, lateral and anteroseptal) that improved during dipyridamole scan, and six had both reversible and irreversible defects: four in a single segment (three anteroseptal and one lateral, and two in two different regions, particularly anteroseptal and lateral, lateral and inferior). All 20 patients showed significantly lower HRV parameters in comparison with the control group, except for pNN50, which indicates decreased physiologic periodic fluctuations of the autonomic nervous system. In six patients who underwent coronary angiography, the epicardial vessels were found completely normal. In view of the high incidence of myocardial hypoperfusion in patients with HRV alterations, the authors hypothesize that autonomic dysfunction may be associated with microvascu

关键词：自主神经系统疾病/病理生理学病例对照研究冠状血管造影术冠状动脉循环/生理学冠状血管/病理生理学双嘧达莫/投药和剂量双嘧达莫/诊断应用心电描记术便携式心脏传导系统/病理生理学心率/生理学心间隔/病理生理学发病率红斑狼疮系统性/病理生理学红斑狼疮系统性/放射性核素显像心肌收缩/生理学心肌炎/病理生理学心肌炎/放射性核素显像心包/病理学放射性药物/诊断应用不应期电生理学/生理学信号处理计算机辅助 99m锝甲氧基异丁基异腈/诊断应用体层摄影术发射型计算机单光子血管舒张药/投药和剂量血管舒张药/诊断应用青少年成年人女(雌)性人类男(雄)性中年人

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Effect of renal impairment on the pharmacokinetics of cilostazol and its metabolites

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CLINICAL PHARMACOKINETICS 1999年第2-Sup期37卷 33-40页

作者： Mallikaarjun, S Forbes, WP Bramer, SL Otsuka Amer Pharmaceut Inc Dept Clin Pharmacokinet Pharmacodynam & Metab Rockville MD 20850 USA

Objective: The pharmacokinetics of cilostazol were studied in patients with mild, moderate and severe renal impairment and in healthy volunteers after administration of 50mg single and multiple doses of cilostazol. Design: This was an open-label, single and multiple dose study administering 50mg cilostazol every 12 hours to healthy volunteers and patients with varying degrees of renal impairment. Participants: 6 normal volunteers [creatinine clearance (CLCR) greater than or equal to 90 ml/min];6 patients with mild (CLCR 50 to 89 ml/min), 5 with moderate (CLCR 26 to 49 ml/min) and 6 with severe (CLCR 5 to 25 ml/min) renal impairment. Outcome Measures: Noncompartmental pharmacokinetic parameters were determined for each study participant. Results: At steady state, in the severe renal disease group, cilostazol and OPC-13015 peak concentrations (C-max) were 24 and 41% lower and the areas under the concentration-time curve over the dosage interval (AUC(tau)) 39 and 47% lower than in the healthy volunteers. C-max and AUC(tau) of OPC-13213 were significantly higher, 173 and 209%, respectively, than those in the healthy volunteers. The accumulation ratios were not significantly different between the various renal function groups for cilostazol and its metabolites. The estimated pharmacological activity of cilostazol and its metabolites was similar between the normal volunteers and those with severe renal impairment. Conclusions: A dosage reduction in renally impaired patients is not supported by the pharmacokinetics of cilostazol and its metabolites in this patient group.

关键词：投药口服方差分析曲线下面积色谱法高压液相肌酸酐/代谢用药计划表半衰期代谢清除率参考值肾功能不全/分类肾功能不全/代谢疾病严重程度指数四唑类/投药和剂量四唑类/血液四唑类/代谢四唑类/药代动力学血管舒张药/投药和剂量血管舒张药/血液血管舒张药/代谢血管舒张药/药代动力学女(雌)性人类男(雄)性中年人

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Exercise training enhances endothelial function in young men

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第5期33卷 1379-1385页

作者： Clarkson, P Montgomery, HE Mullen, MJ Donald, AE Powe, AJ Bull, T Jubb, M World, M Deanfield, JE UCL Hosp Sch Med Hatter Inst Cardiovasc Studies London England Army Training Regiment Dept Physiotherapy Bassingbourn Cambs England Royal Army Med Coll London England

OBJECTIVES The present study was designed to assess whether exercise training can enhance endothelium-dependent dilatation in healthy young men. BACKGROUND Exercise has been shown to reduce cardiovascular morbidity and mortality, but the mechanisms for this benefit are unclear. Endothelial dysfunction is an early event in atherogenesis, and animal studies have shown that exercise training can enhance endothelial function. METHODS We have examined the effect of a standardized, 10-week, aerobic and anaerobic exercise training program on arterial physiology in 25 healthy male military recruits, aged 17 to 24 (mean 20) years, of average fitness levels. Each subject was studied before starting, and after completing the exercise program. Baseline vascular reactivity was compared with that of 20 matched civilian controls. At each visit, the diameter of the right brachial artery was measured at rest, during reactive hyperemia (increased flow causing endothelium-dependent dilation) and after sublingual glyceryltrinitrate (GTN;an endothelium-independent dilator), using high-resolution external vascular ultrasound. RESULTS At baseline, flow-mediated dilatation (FMD) and GTN-mediated dilatation were similar in the exercise and control groups (FMD 2.2 +/- 2.4% and 2.4 +/-: 2.8%, respectively, p = 0.33;GTN 13.4 +/- 6.2 vs. 16.7 +/- 5.9, respectively, p = 0.53). In the military recruits, FMD improved from 2.2 +/- 2.4% to 3.9 +/- 2.5% (p = 0.01), with no change in the GTN-mediated dilation (13.4 +/- 6.2% vs. 13.9 +/- 5.8%, p = 0.31) following the exercise program. CONCLUSION Exercise training enhances endothelium-dependent dilation in young men of average fitness. This may contribute to the benefit of regular exercise in preventing cardiovascular disease. (C) 1999 by the American College of Cardiology.

关键词：投药舌下血流速度肱动脉/诊断显像肱动脉/药物作用肱动脉/生理学胆固醇 HDL/血液内皮血管/诊断显像内皮血管/药物作用内皮血管/生理学运动(Exercise)/生理学纤维蛋白原/代谢随访研究脂蛋白(A)/血液军事人员肌平滑血管/诊断显像肌平滑血管/药物作用肌平滑血管/生理学硝酸甘油/投药和剂量试验预期值参考值回顾性研究超声检查多普勒脉冲血管舒张/生理学血管舒张药/投药和剂量录像青少年成年人人类男(雄)性

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Comparison of safety and efficacy of carvedilol and metoprolol in stable angina pectoris

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第5期83卷 643-649页

作者： van der Does, R Hauf-Zachariou, U Pfarr, E Holtbrügge, W Konig, S Griffiths, M Lahiri, A Boehringer Mannheim GmbH Dept Clin Res D-68305 Mannheim Germany Northwick Pk Hosp & Clin Res Ctr Harrow HA1 3UJ Middx England

In a double-blind, randomized, 3-month multicenter study, the safety and tolerability and the antianginal and anti-ischemic efficacy of carvedilol 25 to 50 mg twice daily were assessed in comparison with metoprolol 50 ta 100 mg twice daily in younger and elderly patients with stable angina. After a 7-day placebo run-in at the end of which a symptom-limited bicycle ergometric exercise was performed, 368 patients were randomly allocated to the parallel treatment groups. After 4 weeks of therapy with a low dose, a further exercise test was performed and patients were titrated in single-blind fashion to the higher dose if the increase in total exercise time was <1 minute, and there was no safety concern. After a further 8 weeks of treatment a third exercise test was performed. Carvedilol low dose/high dose was shown to be at least as safe and well tolerated as metoprolol low dose/high dose both in younger and elderly patients. There were no thitherto unknown adverse events and no marked change in the types of events after increase of the doses. Early adverse events after treatment initiation or uptitration were equal with both medications, indicating no particular risk associated with carvedilol's vasodilatory action. No rebound phenomena were observed. Both drugs showed good antianginal and anti-ischemic efficacy, with marked increases on uptitration including patients greater than or equal to 65 years of age. However, in the doses selected, which appeared equipment with respect to beta blockade, carvedilol's improvement of time to 1-mm ST-segment depression was statistically significantly greater than that of metoprolol. This could be due to its additional vasodilatory or antioxidative actions. Based on the safety and efficacy data of the present study, use of the higher of the 2 recommended doses of carvedilol and metoprolol appears justified in younger and elderly patients without adequate therapeutic control at lower doses. (C)1999 by Excerpta Medico, Inc.

关键词：肾上腺素能α拮抗剂/投药和剂量肾上腺素能α拮抗剂/治疗应用肾上腺素能β受体拮抗剂/投药和剂量肾上腺素能β受体拮抗剂/治疗应用年龄因素心绞痛/药物疗法抗氧化剂/投药和剂量抗氧化剂/治疗应用卡唑类/投药和剂量卡唑类/治疗应用双盲法心电描记术/药物作用运动试验随访研究美托洛尔/投药和剂量美托洛尔/治疗应用心肌缺血/预防和控制安慰剂丙醇胺类/投药和剂量丙醇胺类/治疗应用危险因素安全单盲法时间因素血管舒张药/投药和剂量血管舒张药/治疗应用老年人女(雌)性人类男(雄)性中年人

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The impact of heavy passive smoking on arterial endothelial function in modernized Chinese

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第4期36卷 1228-1232页

作者： Woo, KS Chook, P Leong, HC Huang, XS Celermajer, DS Chinese Univ Hong Kong Dept Med & Therapeut Hong Kong Hong Kong Peoples R China Kiang Wu Hosp Dept Med Macau Peoples R China Univ Sydney Dept Med Sydney NSW 2006 Australia

OBJECTIVES The study evaluated whether heavy exposure to environmental tobacco smoke (passive smoking) might damage arterial function in modernized Chinese. BACKGROUND Heavy passive smoking is associated With arterial endothelial dysfunction in Caucasian, but not rural Chinese, subjects. METHODS We studied 20 young (mean age 36.6 +/- 7.0 years) nonsmoking asymptomatic casino workers (9 men) in Macau who were exposed to environmental tobacco smoke for over 8 h/day for at least two years and 20 normal subjects (control subjects). These two groups were carefully matched for age, gender, body mass index (BMI), blood pressure, vessel diameter, cholesterol and glucose levels. Brachial artery diameter was measured by high-resolution B-mode ultrasound at rest, after flow increase (causing flow-mediated endothelium-dependent dilation) and after sublingual nitroglycerin tan endothelium-independent dilator). RESULTS Flow-mediated dilation (mean +/- SD% of diameter changes) was significantly lower in passive smokers (6.6 +/- 3.4%) compared with the controls (10.6 +/- 2.3%) (p < 0.0001). Nitroglycerin-induced dilation of the two groups were similar. Upon multivariate analysis, passive smoking exposure was the strongest independent predictor (beta = -0.59;p = 0.0001) for impaired flow-mediated endothelium-dependent dilation (model R-2 = 0.75, F value = 6.1, p = 0.0001). CONCLUSIONS In modernized Chinese, as in Caucasians, exposure to heavy environmental tobacco smoke causes arterial endothelial dysfunction, a key early event in atherosclerosis. This may have serious implications for cardiovascular health in China, currently in a process of rapid modernization. CT Am Cell Cardiol 2000;36:1228-32) (C) 2000 by the American College of Cardiology.

关键词：投药舌下动脉硬化/流行病学动脉硬化/病因学动脉硬化/病理生理学亚洲大陆世系人群血流速度/药物作用血流速度/生理学肱动脉/诊断显像肱动脉/药物作用肱动脉/病理生理学内皮血管/药物作用内皮血管/病理生理学赌博澳门/流行病学硝酸甘油/投药和剂量烟草烟污染/副作用超声检查血管舒张/药物作用血管舒张/生理学血管舒张药/投药和剂量成年人女(雌)性人类男(雄)性

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