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Alpha-adrenoceptor blockade prevents exercise-induced vasoconstriction of stenotic coronary arteries

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第6期33卷 1499-1505页

作者： Julius, BK Vassalli, G Mandinov, L Hess, OM Inselspital Bern Swiss Heart Ctr CH-3010 Bern Switzerland Univ Zurich Hosp Dept Internal Med Zurich Switzerland

OBJECTIVES The study aimed to evaluate the role of alpha-adrenergic mechanisms during dynamic exercise in both normal and stenotic coronary arteries. BACKGROUND Paradoxical vasoconstriction of stenotic coronary arteries has been reported during dynamic exercise and may be due to several factors such as alpha-adrenergic drive, a decreased release of nitric oxide, platelet aggregation with release of serotonin, or a passive collapse of the vessel wall. METHODS Twenty-six patients were studied at rest, during two levels of supine bicycle exercise and after 1.6 mg sublingual nitroglycerin The alpha-blocker phentolamine was given to 16 patients before exercise, five of whom had also taken a beta-adrenergic-blocker the same morning. Ten patients served as controls. The cross-sectional areas of a normal and a stenotic coronary vessel were determined by biplane quantitative coronary arteriography. RESULTS In the normal vessel segments, coronary cross-sectional area did not change after phentolamine injection, but increased in all patient groups similarly during exercise. Although coronary vasoconstriction existed in stenotic vessel segments in control patients, phentolamine-treated patients showed exercise-induced vasodilation without difference in Twenty-six patients were patients with and without chronic beta-blockade. CONCLUSIONS Exercise-induced vasoconstriction of stenotic coronary arteries is prevented by intracoronary administration of phentolamine There was no difference in coronary vasomotion between patients receiving phentolamine alone;md patients receiving phentolamine in addition to a beta-blocker. This finding suggests that exercise-induced vasoconstriction is mediated not only by endothelial dysfunction but also by alpha-adrenergic mechanisms. (C) 1999 by the American College of Cardiology.

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/副作用肾上腺素能β受体拮抗剂/投药和剂量肾上腺素能β受体拮抗剂/副作用阿替洛尔/投药和剂量阿替洛尔/副作用冠状血管造影术/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/病理生理学运动试验/药物作用血流动力学/药物作用美托洛尔/投药和剂量美托洛尔/副作用硝酸甘油/投药和剂量硝酸甘油/副作用酚妥拉明/投药和剂量酚妥拉明/副作用术前用药法血管收缩/药物作用血管收缩/生理学血管舒张药/投药和剂量血管舒张药/副作用成年人老年人女(雌)性人类男(雄)性中年人

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Low-dose dipyridamole infusion acutely increases exercise capacity in angina pectoris - A double-blind, placebo controlled crossover stress echocardiographic study

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第1期35卷 83-88页

作者： Tommasi, S Carluccio, E Bentivoglio, M Corea, L Picano, E CNR Inst Clin Physiol I-56100 Pisa Italy Univ Perugia Dept Clin & Expt Med Cardiol Unit Perugia Italy

OBJECTIVES The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia. BACKGROUND Adenosine is a recognized mediator of ischemic preconditioning in experimental settings. METHODS Ten patients (all men: mean age 63.4 +/- 7.3 years) with chronic stable angina, angiographically assessed coronary artery disease (n = 7) or previous myocardial infarction (n = 3) and exercise-induced ischemia underwent on different days two exercise-stress echo tests after premedication with placebo or dipyridamole (15 mg in 30 min, stopped 5 min before testing) in a double-blind, placebo controlled, randomized crossover design. RESULTS In comparison with placebo, dipyridamole less frequently induced chest pain (20% vs. 100%, p = 0.001) and >0.1 mV ST segment depression (50% vs. 100%, p < 0.05). Wall motion abnormalities during exercise-stress test were less frequent (placebo = 100% vs. dipyridamole = 70%, p = ns) and significantly less severe (wall motion score index at peak stress: placebo = 1.55 +/- 0.17 vs, dipyridamole = 1.27 +/- 0.2, p < 0.01) following dipyridamole, which also determined an increase in exercise time up to echocardiographic positivity (placebo = 385.9 +/- 51.4 vs. dipyridamole = 594.4 +/- 156.9 s, p < 0.01). CONCLUSIONS Low-dose dipyridamole infusion increases exercise tolerance in chronic stable angina, possibly by endogenous adenosine accumulation acting on high affinity Al myocardial receptors involved in preconditioning or positively modulating coronary flow through collaterals. (C) 1999 by the American College of Cardiology.

关键词：腺苷/代谢心绞痛/药物疗法心绞痛/病理生理学交叉研究双嘧达莫/投药和剂量双嘧达莫/副作用剂量效应关系药物双盲法运动试验/药物作用术前用药法受体嘌呤能P1/药物作用受体嘌呤能P1/生理学血管舒张药/投药和剂量血管舒张药/副作用老年人女(雌)性人类男(雄)性中年人

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The potential for QT prolongation and pro-arrhythmia by non-anti-arrhythmic drugs: Clinical and regulatory implications Report on a Policy Conference of the European Society of Cardiology

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CARDIOVASCULAR RESEARCH 2000年第2期47卷 219-233页

作者： Haverkamp, W Breithardt, G Camm, AJ Janse, MJ Rosen, MR Antzelevitch, C Escande, D Franz, M Malik, M Moss, A Shah, R Univ Hosp Dept Cardiol & Angiol Munster Germany Masonic Med Res Utica NY USA St George Hosp London England Fac Med Dept Physiol Nantes France Dept Vet Affairs Med Ctr Washington DC USA Univ Amsterdam Acad Med Ctr NL-1105 AZ Amsterdam Netherlands Univ Rochester Med Ctr Rochester NY 14642 USA Columbia Univ Coll Phys & Surg New York NY 10032 USA Med Control Agcy London England

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Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第4期34卷 1188-1192页

作者： Nagaya, N Uematsu, M Okano, Y Satoh, T Kyotani, S Sakamaki, F Nakanishi, N Miyatake, K Kunieda, T Natl Cardiovasc Ctr Dept Med Div Cardiol Suita Osaka 565 Japan Osaka Police Hosp Div Cardiovasc Osaka Japan Kyoto Univ Hosp Dept Clin Lab Med Kyoto 606 Japan Keio Univ Ise Keio Hosp Dept Med Ise Mie Japan

OBJECTIVES This study sought to investigate the effect of beraprost sodium (BPS), an orally active prostacyclin analogue, on the survival of outpatients with primary pulmonary hypertension (PPH). BACKGROUND Continuous intravenous administration of epoprostenol (prostacyclin) has been shown to improve survival in PPH. However, the effect of oral BPS on survival in PPH remains unknown. METHODS Fifty-eight consecutive patients with PPH who could be discharged after the first diagnostic catheterization for PPH were retrospectively divided into two groups: patients treated with BPS (BPS group, n = 24) and those without BPS (conventional group, n = 34). The baseline demographic and hemodynamic data did not significantly differ between the two. RESULTS Twenty-seven patients died of cardiopulmonary causes in the conventional group during a mean follow-up period of 44 +/- 45 months. In contrast, only 4 patients died of cardiopulmonary causes in the BPS group during a mean follow-up period of 30 +/- 20 months. In a subsample (n = 15) of patients in the BPS group, mean pulmonary arterial pressure and total pulmonary resistance significantly decreased, respectively, by 13% and 25% during a mean follow-up period of 53 days. Among the variables previously known to be associated with the mortality in PPH, the absence of BPS therapy and the reduced cardiac output were independently related to the mortality by a multivariate Cox proportional hazards regression analysis (both p < 0.05). The Kaplan-Meier survival curves demonstrated that the one-, two- and three-year survival rates far the BPS group were 96%, 86% and 76%, respectively, as compared with 77%, 47% and 44%, respectively, in the conventional group (log-rank test, p < 0.05). CONCLUSIONS The oral administration of BPS may have beneficial effects on the survival of outpatients with PPH as compared with conventional therapy alone. (J Am Coll Cardiol 1999;34:1188-92) (C) 1999 by the American College of Cardiology.

关键词：投药口服死亡原因剂量效应关系药物依前列醇/投药和剂量依前列醇/副作用依前列醇/类似物和衍生物血流动力学/药物作用高血压肺性/药物疗法高血压肺性/死亡率回顾性研究存活率血管舒张药/投药和剂量血管舒张药/副作用成年人女(雌)性人类男(雄)性中年人

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High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第3期36卷 832-837页

作者： Sharon, A Shpirer, I Kaluski, E Moshkovitz, Y Milovanov, O Polak, R Blatt, A Simovitz, A Shaham, O Faigenberg, Z Metzger, M Stav, D Yogev, R Golik, A Krakover, R Vered, Z Cotter, G Assaf Harofeh Med Ctr Cardiol Inst IL-70300 Zerifin Israel Assaf Harofeh Med Ctr Dept Med IL-70300 Zerifin Israel Assaf Harofeh Med Ctr Dept Pulmonol IL-70300 Zerifin Israel Assaf Harofeh Med Ctr Clin Pharmacol Res Unit IL-70300 Zerifin Israel Magen David Adom EMS Serv Zerifin Israel

OBJECTIVES To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy. BACKGROUND Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities. METHODS We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival. RESULTS Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or hi) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of. treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee. CONCLUSIONS

关键词：剂量效应关系药物注射静脉内硝酸异山梨酯/投药和剂量硝酸异山梨酯/副作用硝酸异山梨酯/治疗应用氧/血液正压呼吸/副作用正压呼吸/方法肺水肿/血液肺水肿/药物疗法肺水肿/治疗治疗结果血管舒张药/投药和剂量血管舒张药/副作用血管舒张药/治疗应用女(雌)性人类男(雄)性

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Nicorandil and diabetes: a nested case-control study to examine a signal generated by prescription-event monitoring

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EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 1999年第2期55卷 159-162页

作者： Dunn, N Freemantle, S Mann, R Drug Safety Res Unit Southampton Hants England

Objective: To investigate a signal generated by an observational cohort study that treatment with the potassium channel opener drug, nicorandil, is associated with an increased incidence of diabetes mellitus (DM). Methods: Nested case-control study within cohorts used for prescription-event monitoring. Results: The cohort study of nicorandil showed that there was a significant difference between the event rate for DM in the first month after starting nicorandil, compared to months 2-6 (difference in rates 1.93, 99% CI 0.7-3.1, per 1000 patient months of treatment). However, the adjusted odds ratio from the case-control study was 1.42 (95% CI 0.66-3.07) for incidence of newly diagnosed DM in nicorandil versus four comparator drugs. Conclusions: The nested case-control study was used as a hypothesis-testing instrument for following up a signal of a possible drug reaction to nicorandil. It showed no evidence that nicorandil is associated with increased incidence of newly diagnosed DM.

关键词：抗心律失常药/副作用病例对照研究糖尿病/流行病学发病率尼可地尔/副作用危险血管舒张药/副作用老年人女(雌)性人类男(雄)性中年人

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