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Comparison of diagnostic accuracy of sublingual nitroglycerin test and low-dose isoproterenol test in patients with unexplained syncope

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第10期85卷 1194-1198页

作者： Raviele, A Giada, F Brignole, M Menozzi, C Marangoni, E Manzillo, GF Alboni, P Osped Umberto 1 Unita Operat Cardiol Div Cardiol I-30174 Venice Italy Osped Riuniti Bergamo Sect Arrhythomol Lavagna Genoa Italy Osped S Maria Nuova Sect Arrhythmol Reggio Emilia Italy Osped Maggiore Div Cardiol Lodi Milano Italy Osped Valduce Serv Cardiol Como Italy Osped Civile Div Cardiol Cento Ferrara Italy

Despite the widespread use of head-up tilt testing as a means for diagnosing vasovagal syncope, standardization of test methodology remains a controversial issue. The aim of this study was to compare the diagnostic value of head-up tilt testing potentiated with sublingual nitroglycerin with that of head-vp tilt testing potentiated with law-dose isoproterenol. For this purpose, 71 patients with unexplained syncope (mean age 43 years) and 30 asymptomatic controls were studied. All underwent the sublingual nitroglycerin and low-dose isoproterenol tests on separate days in a randomized fashion. The protocol of the 2 tests was similar and consisted of 2 phases. Initially, subjects were tilted at 60 degrees for 20 minutes without medication;then, if syncope did not occur, patients and controls received sublingual nitroglycerin (300 mu g) or low-dose intravenous isoproterenol (mean infusion rate 1.3 +/- 0.5 mu g/min) and continued to be tilted at 60 degrees for a further 20 minutes. During the sublingual nitroglycerin test, a positive response (syncope associated with sudden hypotension and bradycardia) occurred in 35 patients (49%), a negative response in 36 (51%), and drug intolerance in none (0%). During the low-dose isoproterenol test, these percentages were 41%, 59%, and 6%, respectively. A concordant response was observed in 53 cases (75%). Among controls, 3 subjects (10%) had a positive response to the sublingual nitroglycerin test and 4 (13%) to the low-dose isoproterenol test. It is concluded that sublingual nitroglycerin and low-dose isoproterenol are equivalent tests for evaluating patients with unexplained syncope. The sublingual nitroglycerin test, however, is simpler, better tolerated, and safer than the low-dose isoproterenol test and, thus, more suitable for routine clinical use. (C) 2000 by Excerpta Medica, Inc.

关键词：投药舌下血压强心药/投药和剂量强心药/诊断应用心率输注静脉内异丙肾上腺素/投药和剂量异丙肾上腺素/诊断应用多元分析硝酸甘油/投药和剂量硝酸甘油/诊断应用试验预期值晕厥血管迷走神经性/诊断倾斜台试验血管舒张药/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

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Temporal response of brachial artery dilation after occlusion and nitroglycerin

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第3期85卷 396-+页

作者： Bressler, B Chan, S Mancini, GBJ Univ British Columbia Dept Med Div Cardiol St Pauls HospAtherosclerosis Reversal Clin Vancouver BC V6T 1W5 Canada Jack bell Res Ctr Vancouver BC Canada

This study shows that a set time after cuff deflation or after nitroglycerin administration may not be suitable to capture peak, brachial artery dilatory responses in assessing endothelial dysfunction. Automated, cont... 详细信息

关键词：投药舌下肱动脉/药物作用肱动脉/生理学肱动脉/超声检查冠心病/诊断内皮血管/药物作用前臂/血液供给硝酸甘油/投药和剂量硝酸甘油/药理学试验预期值局部血流/药物作用时间因素血管舒张药/投药和剂量血管舒张药/药理学女(雌)性人类男(雄)性

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Reproducibility of head-up tilt testing potentiated with sublingual nitroglycerin in patients with unexplained syncope

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第3期84卷 284-288页

作者： Foglia-Manzillo, G Giada, F Beretta, S Corrado, G Santarone, M Raviele, A Osped Gen Valduce Serv Cardiol Dept Cardiol I-22100 Como Italy Osped Gen Valduce Dept Neurol I-22100 Como Italy Osped Umberto 1 Dept Cardiol Mestre Italy

Head-up tilt testing (HUTT) potentiated with sublingual nitroglycerin has gained acceptance as means of diagnosing neurally mediated syncope. To evaluate the reproducibility of HUTT potentiated with sublingual nitroglycerin, 48 patients with unexplained syncope prospectively underwent 2 consecutive tests 1 to 28 days apart. The initial test ended in syncope in 34 patients (71%). In 9 patients (19%) the test was positive during the drug-free phase, whereas 25 patients (52%) had syncope after nitroglycerin administration. Of these 34 patients with an initial positive test result, 27 (79%) had a reproducible outcome on repeat testing. Of 12 patients (25%) with an initial negative test result, 10 (83%) had a reproducible outcome on repeat testing. Of 2 patients (4%) with a first test ending in exaggerated response, both had a negative repeat test response. The overall reproducibility of sublingual nitroglycerin tilt-table testing was 77%. In a group of 23 patients with both positive tests, 19 (83%) had the same response modality (2 vasodepressor, 4 cardioinhibitory, 13 mixed response). In the same group of patients, individual trough heart rates correlated well with each other between tests. Finally, in the 27 patients with both positive tests, intrapatient time of onset of symptoms did not significantly correlate between tests. Thus, in patients with syncope of unknown origin, HUTT potentiated with sublingual nitroglycerin provides an adequate reproducibility when repeated on different days. (C) 1999 by Excerpta Medico, Inc.

关键词：投药舌下诊断鉴别硝酸甘油/投药和剂量硝酸甘油/诊断应用可重复性结果晕厥/病因学倾斜台试验/方法时间因素血管舒张药/投药和剂量血管舒张药/诊断应用青少年成年人老年人儿童女(雌)性人类男(雄)性中年人

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Role of incremental doses of intracoronary adenosine for fractional flow reserve assessment

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AMERICAN HEART JOURNAL 2003年第1期146卷 99-105页

作者： Murtagh, B Higano, S Lennon, R Mathew, V Holmes, DR Lerman, A Mayo Clin & Mayo Fdn Ctr Coronary Physiol & Imaging Div Cardiovasc Dis Rochester MN 55905 USA Mayo Clin & Mayo Fdn Dept Internal Med Rochester MN 55905 USA Mayo Clin & Mayo Fdn Div Biostat Rochester MN 55905 USA

Background The achievement of maximal vasodilatation of the coronary microvessels is mandatory for the accurate determination of fractional flow reserve (FFR);the optimal dosing to achieve maximal vasodilation is unclear. This study was designed to address the hypothesis that incremental doses of intracoronary adenosine are necessary to ensure complete vasodilatation of the coronary microcirculation and accurate assessment of FFR. We also examined the relationship between FFR and coronary artery disease risk factors. Methods A total of 191 patients (215 vessels) with intermediate coronary lesions were examined. FFR was measured during cardiac catheterization with a pressure monitoring wire. Incremental doses of intracoronary adenosine (12-42 mug, left coronary artery;12-48 mug, right coronary artery) were administered. Results Diabetes mellitus was present in 23% of patients, hypertension was present in 65% of patients, and prior myocardial infarction had occurred in 25% of patients. The average percent stenosis in vessels was 57% +/- 15%. Vessels were subdivided on the basis of initial FFR (group I, <0.75;group II, 0.75-0.79;group III, 0.80-0.89;group IV, 0.9). Five of the 24 (21%) vessels with an initial FFR in the 0.75 to 0.80 range had a subsequent FFR of <075. There was no difference in FFR or doses of adenosine in the patients with coronary artery disease risk factors. The average adenosine dose given at the achievement of minimal FFR was 26 mug in the right coronary artery (RCA) and 34 mug in the left coronary artery (LCA). The average maximum dose of intracoronary,adenosine administered was 29 mug for the RCA and 37 mug for the LCA. The maximum dose of adenosine ever required to achieve minimum FFR was 42 mug in both the LCA and RCA. Conclusion This study suggests that a single high dose of 42 mug of intracoronary adenosine for both the RCA and LCA is sufficient to achieve maximum hyperemia and accurate FFR in most patients, independent of risk factors. Alte

关键词：腺苷/投药和剂量方差分析血流速度/药物作用血流速度/生理学冠状动脉循环/药物作用冠状动脉循环/生理学冠状动脉狭窄/药物疗法冠状动脉狭窄/病理生理学冠状血管/药物作用冠状血管/生理学充血/化学诱导充血/病理生理学注射动脉内微循环/药物作用微循环/生理学血管舒张血管舒张药/投药和剂量老年人女(雌)性人类男(雄)性中年人

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Effects of supraspinal orphanin FQ/nociceptin

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PEPTIDES 2000年第7期21卷 1037-1045页

作者： Grisel, JE Mogil, JS Furman Univ Dept Psychol Greenville SC 29613 USA Univ Illinois Dept Psychol Champaign IL 61820 USA Univ Illinois Program Neurosci Champaign IL 61820 USA

The first reported behavioral action of the endogenous ligand for the "orphan" opioid receptor was a seemingly paradoxical increased sensitivity to nociception (i.e, hyperalgesia) after supraspinal injection into the cerebral ventricles of mice. In the continuing absence of an appropriate in vivo receptor antagonist, studies attempting to define the role of orphanin FQ/nociceptin (OFQ/N) in pain modulation and other behaviors have also featured central injection of peptide. This article reviews the findings of such studies. There appears to be concordance around the observation of anti-opioid actions of supraspinally injected OFQ/N, whereas the observations of hyperalgesia and/or analgesia are much less clear. A portion of the discrepant data may be explained in terms of methodological issues, stress-induced analgesia accompanying experimental protocols, and genotypic variation among subjects. Clarification of OFQ/N's role in nociception, as with other putative biologic functions, will probably depend upon the availability of a selective receptor antagonist. (C) 2000 Elsevier Science Inc. All rights reserved.

关键词：镇痛药/药理学基因型小鼠基因敲除阿片样肽类/投药和剂量阿片样肽类/拮抗剂和抑制剂阿片样肽类/遗传学阿片样肽类/药理学肽类/化学肽类/药理学表型血管舒张药/投药和剂量血管舒张药/拮抗剂和抑制剂血管舒张药/药理学动物小鼠大鼠

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Endothelial vasodilator function is related to low-density lipoprotein particle size and low-density lipoprotein vitamin E content in type 1 diabetes

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第2期35卷 292-299页

作者： Skyrme-Jones, RAP O'Brien, RC Luo, M Meredith, IT Monash Med Ctr Ctr Heart & Chest Res Melbourne Vic Australia Monash Med Ctr Dept Med Melbourne Vic Australia Monash Univ Melbourne Vic 3004 Australia

OBJECTIVES We sought to determine whether endothelial vasodilator function (EVF) in patients with type 1 diabetes was related to low-density lipoprotein (LDL) particle size (LDLPS), LDL vitamin E content (LDLVE) or the susceptibility of LDL to oxidation (OxLDL). BACKGROUND Impaired EVF is an early feature of diabetic vascular disease and may be related to oxidant stress. Although small, dense LDL and oxidized LDL are features of type 2 diabetes and predict the development of coronary artery disease, their role in type 1 diabetes is less clear. METHODS Endothelium-dependent vasodilation was assessed in the brachial artery (flow-mediated vasodilation [FMD]) and in the forearm resistance circulation using venous occlusion plethysmography in response to graded doses of intrabrachial acetylcholine (ACh). Thirty-seven patients with type 1 diabetes mellitus (DM) and 45 matched controls underwent flow-mediated dilation, while a subset of 19 DM and 20 controls underwent plethysmography. RESULTS Total, LDL and high-density lipoprotein cholesterol or triglycerides were not different in DM compared with controls, but LDLPS was smaller (25.6 +/- 0.06 vs. 26.1 +/- 0.1 nm, p < 0.05) and LDLVE was reduced (2.0 +/- 0.25 vs. 2.6 +/- 0.18 mu mol/mmol LDL, p < 0.05). Oxidative susceptibility of LDL was not different. Flow-mediated vasodilation was impaired in DM compared with controls (3.6 +/- 0.6% vs. 7.1 +/- 0.5%, p < 0.005), as was the vasodilator response to ACh (p < 0.05). Flow-mediated vasodilation was directly related to LDLPS and LDLVE in both the entire study cohort and DM alone (p < 0.05), but not to other parameters of the standard lipid profile. Similarly, endothelium-dependent vasodilation in the resistance circulation was directly related to LDLPS and LDLVE, but not to OxLDL. CONCLUSION These results suggest, but do not prove, that LDL particle size and LDL vitamin E may be determinants of conduit and resistance vessel endothelial vasodilator function in type 1 diabetes.

关键词：乙酰胆碱/投药和剂量血流速度肱动脉/诊断显像肱动脉/药物作用肱动脉/病理生理学胆固醇 LDL/血液糖尿病 1型/血液糖尿病 1型/病理生理学内皮血管/药物作用内皮血管/病理生理学输注动脉内硝酸甘油/投药和剂量硝普钠/投药和剂量氧化性应激预后危险因素超声检查血管舒张/药物作用血管舒张/生理学血管舒张药/投药和剂量维生素E/血液成年人人类

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Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第3期33卷 813-819页

作者： Atz, AM Adatia, I Lock, JE Wessel, DL Harvard Univ Childrens Hosp Dept Cardiol Sch MedCardiac ICU Off Boston MA 02115 USA Harvard Univ Sch Med Dept Pediat Boston MA 02115 USA

OBJECTIVES. We compared the ability of inhaled nitric oxide (NO), oxygen (O-2) and nitric oxide in oxygen (NO+O-2) to identify reactive pulmonary vasculature in pulmonary hypertensive patients during acute vasodilator testing at cardiac catheterization. BACKGROUND. In patients with pulmonary hypertension, decisions regarding suitability for corrective surgery, transplantation and assessment of long-term prognosis are based on results obtained during acute pulmonary vasodilator testing. METHODS. In group 1, 46 patients had hemodynamic measurements in room air (RA), 100% O-2, return to RA and NO (80 parts per million [ppm] in Rtl). In group 2, 25 additional patients were studied in RA, 100% O-2 and 80 ppm NO in oxygen (NO+O-2). RESULTS. In group 1, O-2 decreased pulmonary vascular resistance (PVR) (mean +/- SEM) from 17.2 +/- 2.1 U.m(2) to 11.1 +/- 1.5 U.m(2) (P < 0.05). Nitric oxide caused a comparable decrease from 17.8 +/- 2.2 U.m(2) to 11.7 +/- 1.7 U.m(2) (p < 0.05). In group 2, PVR decreased from 20.1 +/- 2.6 U.m(2) to 14.3 +/- 1.9 U.m(2) in O-2 (p < 0.05) and further to 10.5 +/- 1.7 U.m(2) in NO+O-2, (p < 0.05). A response of 20% or more reduction in PVR was seen in 22/25 patients with NO+O-2 compared with 16/25 in O-2 alone (p = 0.01). CONCLUSIONS. Inhaled NO and O-2 produced a similar degree of selective pulmonary vasodilation. Our data suggest that combination testing with NO+O-2 provides additional pulmonary vasodilation in patients with a reactive pulmonary vascular bed in a selective, safe and expeditious fashion during cardiac catheterization. The combination of NO+O-2 identifies patients with significant pulmonary vasoreactivity who might not be recognized if O-2 or NO were used separately.(C) 1999 by the American College of Cardiology.

关键词：投药吸入高血压肺性/诊断高血压肺性/病理生理学高血压肺性/治疗一氧化氮/投药和剂量氧吸入疗法预后肺动脉/药物作用肺动脉/病理生理学肺循环/药物作用肺楔压回顾性研究血管阻力/药物作用血管舒张/药物作用血管舒张药/投药和剂量青少年成年人老年人儿童儿童学龄前人类婴儿中年人

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Cilostazol pharmacokinetics after single and multiple oral doses in healthy males and patients with intermittent claudication resulting from peripheral arterial disease

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CLINICAL PHARMACOKINETICS 1999年第2-Sup期37卷 1-11页

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

Objective: To study the pharmacokinetics of cilostazol following single oral administration of 50 to 200mg in healthy young males, and after repeated oral administration of 100mg every 12 hours to patients with peripheral arterial disease (PAD). Design: The healthy male single dose study was a single-centre, randomised sequence, open-label, incomplete block, 3-period, 4-treatment, crossover design. The patient study was a single-centre, multiple dose, open-label study. Study Participants: 20 healthy nonsmoking male volunteers were enrolled and successfully completed the single dose study. 26 patients (21 males, 5 females) with intermittent claudication resulting from PAD were enrolled and completed the single/multiple dose study. Main Outcome Measures: Noncompartmental pharmacokinetic parameters, the area under the plasma concentration-time curve from zero to the time of last measurable plasma concentration, and maximum plasma concentration. Results: Peak plasma concentrations of cilostazol occurred about 3 hours after drug administration and then declined biexponentially with concentrations detectable (>20 mu g/L) in the plasma for at least 36 hours postdose. The apparent elimination half-life of cilostazol (approximately 11 hours) was similar after a single dose or after multiple doses, with steady state being reached within 4 days. Cilostazol accumulated 1.7-fold following multiple dose administration. The apparent volume of distribution (V-2/F;2.76 L/kg) suggested extensive distribution of cilostazol in the tissues. The oral clearance of cilostazol (CL/F;0.18 L/h/kg) was much lower than liver blood flow, indicating a low extraction ratio drug, and hence low probability of a significant first-pass effect. None of the administered doses were recovered in the urine as unchanged cilostazol, suggesting that metabolism, rather than urinary excretion, is the major elimination route. Following single oral doses of 50 to 200mg, the plasma concentrations of cilostazol and

关键词：投药口服方差分析曲线下面积交叉研究用药计划表间歇性跛行/药物疗法间歇性跛行/病因学代谢清除率外周血管疾病/并发症外周血管疾病/药物疗法四唑类/投药和剂量四唑类/血液四唑类/药代动力学四唑类/治疗应用组织分布血管舒张药/投药和剂量血管舒张药/血液血管舒张药/药代动力学血管舒张药/治疗应用女(雌)性人类男(雄)性

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Adequacy of intracoronary versus intravenous adenosine-induced maximal coronary hyperemia for fractional flow reserve measurements

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AMERICAN HEART JOURNAL 2000年第4期140卷 651-657页

作者： Jeremias, A Whitbourn, RJ Filardo, SD Fitzgerald, PJ Cohen, DJ Tuzcu, M Anderson, WD Abizaid, AA Mintz, GS Yeung, AC Kern, MJ Yock, PG Stanford Univ Med Ctr Ctr Res Cardiovasc Intervent Dept Cardiovasc MedSch Med Stanford CA 94305 USA Harvard Univ Beth Israel Deaconess Med Ctr Sch Med Dept Cardiovasc Med Boston MA 02215 USA Cleveland Clin Fdn Dept Cardiovasc Med Cleveland OH 44195 USA Emory Univ Dept Cardiovasc Med Atlanta GA 30322 USA Washington Hosp Ctr Dept Cardiovasc Med Washington DC 20010 USA St Louis Univ Dept Cardiovasc Med St Louis MO 63103 USA

Background Fractional flow reserve (FFR) is a measure of coronary stenosis severity that is based on pressure measurements obtained at maximal hyperemia. The most widely used pharmacologic stimulus for maximal coronary hyperemia is adenosine, administered either as a continuous intravenous (IV) infusion or intracoronary (IC) bolus. IV adenosine has more side effects and is more costly than IC adenosine but has a more stable and prolonged hyperemic effect. Methods We compared the efficacy of IC and IV adenosine administration for the measurement of FFR in a multicenter trial. Fifty-two patients with 60 lesions underwent determination of FFR with both IV and IC adenosine. IV adenosine was administered as a continuous infusion at a rate of 140 mu g/ka. per minute until a steady state hyperemia was achieved. IC adenosine boluses were administered at a dose of 15 to 20 mu g in the right and 18 to 24 mu g in the left coronary artery. FFR was calculated as the ratio of the distal coronary pressure (from pressure guide wire) to the aortic pressure (guide catheter) at maximal hyperemia. Results A total of 26 left anterior descending, 23 right, 9 left circumflex, and 3 left main coronary arteries were evaluated. Mean percent stenosis for both groups was 55.8% +/- 23.6% (range 0% to 95%), and mean FFR was 0.78 +/- 0.15 (range 0.41 to 0.98). There was a strong and linear correlation between FFR measurements with IV and IC adenosine (R = 0,978, y = 0.032 + 0.964x, P < .001). The agreement between the 2 sets of measurements was also high, with a mean difference in FFR of -0.004 +/- 0.03. However, a small random scatter in both directions of FFR measurements was noted with 5 lesions (8.3%) where FFR with IC adenosine was higher by 0.05 or more compared with IV infusions, suggesting a suboptimal hyperemic response in these patients. Changes in heart rate and blood pressure were significantly higher with IV adenosine. Two patients with IV, but none with IC adenosine, had severe side

关键词：腺苷/投药和剂量血流速度/药物作用血压/药物作用冠状动脉循环/药物作用冠状动脉循环/生理学冠心病/药物疗法冠心病/病理生理学冠状血管/药物作用冠状血管/病理生理学充血/化学诱导充血/病理生理学输注动脉内输注静脉内试点项目安全血管舒张/药物作用血管舒张药/投药和剂量成年人老年人老年人 80以上女(雌)性人类男(雄)性中年人

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A novel S-nitrosothiol (RIG200) causes prolonged relaxation in dorsal hand veins with damaged endothelium

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CLINICAL PHARMACOLOGY & THERAPEUTICS 2000年第1期68卷 75-81页

作者： Sogo, N Wilkinson, IB MacCallum, H Khan, SQ Strachan, FE Newby, DE Megson, IL Webb, DJ Univ Edinburgh Western Gen Hosp Clin Pharmacol Unit Edinburgh EH8 9YL Midlothian Scotland Univ Edinburgh Western Gen Hosp Res Ctr Edinburgh EH8 9YL Midlothian Scotland

Background: Reduced nitric oxide bioavailability caused by endothelial dysfunction or damage is a contributory factor in the initiation and progression of a number of cardiovascular diseases. Delivery of exogenous nitric oxide is an attractive therapeutic option, but current agents lack selectivity for areas of endothelial damage. We tested the hypothesis that a novel nitric oxide donor drug, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deo 1,3,4,6-tetra-O-acetyl-beta-glucopyranose [RIG200], which has selective effects in endothelium-denuded isolated arteries in vitro, would exert similar effects in dorsal hand veins with experimentally damaged endothelium in vivo. Methods: Venodilator responses to sodium nitroprusside and RIG200 were compared in two groups of healthy volunteers (age range, 18 to 63 years;n = 7 for each group) in norepinephrine 70% maximum effective concentration (EC70) preconstricted hand veins with use of the Aellig technique. In this double-blind study, subjects were randomly assigned to receive either sodium nitroprusside or RIG200 (infusions of 0.06 and 6 nmol/min into the hand vein) before and 2 days after 15 minutes of local venous irrigation with distilled water, Endothelial function was assessed in all subjects on both visits with use of the endothelium-dependent vasodilator acetylcholine (1 nmol/min). Results: Irrigation of hand veins with distilled water abolished endothelium-dependent dilatation in response to acetylcholine in both study groups (n = 14) but did not affect the amplitude or duration of responses to the conventional nitric oxide donor sodium nitroprusside (P = .87;n = 7), However, responses to RIG200 were significantly prolonged during the washout phase (30 minutes) in veins after water irrigation (P = .02;n = 7), Conclusion: These studies confirm that RIG200 has prolonged effects in veins with damaged endothelium, a characteristic that might be exploited therapeutically to target nitric oxide delivery to damaged blood ves

关键词：乙酰胆碱/药理学曲线下面积双盲法内皮血管/药物作用内皮血管/生理学输注静脉内灌洗巯基乙醇硝普钠/投药和剂量硝普钠/药理学亚硝基化合物/投药和剂量亚硝基化合物/药理学参考值 S-亚硝基硫醇时间因素血管舒张/药物作用血管舒张药/投药和剂量血管舒张药/药理学水成年人人类男(雄)性中年人

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