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中华内科杂志 1990年第2期29卷 114-115+129页

作者：吴可光王丽君王之章姜卫国中国医科大学附属第三医院内科中国医科大学附属第三医院病理科

大剂量异搏停长期口服治疗肥厚型心肌病(HCM),从临床症状、左室功能及治疗前后心肌活组织检查的连续观察、探讨异搏停对HCM的影响。资料与方法根据临床检查、ECG、UCG、左心室造影,放射性核素心室显像(ECT)、磁共振及心内膜心肌活组织检... 详细信息

大剂量异搏停长期口服治疗肥厚型心肌病(HCM),从临床症状、左室功能及治疗前后心肌活组织检查的连续观察、探讨异搏停对HCM的影响。资料与方法根据临床检查、ECG、UCG、左心室造影,放射性核素心室显像(ECT)、磁共振及心内膜心肌活组织检查(EMCB)确诊为原发性肥厚型心肌病3例。2例为非梗阻型,1例梗阻型,均为男性。年龄为31、34和49岁。病程2、7及9年。各服异

关键词：投药口服维拉帕米/投药和剂量维拉帕米/治疗应用心肌病肥厚性/病理学心肌病肥厚性/药物疗法人类

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Comparison of controlled-onset, extended-release verapamil with amlodipine and amlodipine plus atenolol on exercise performance and ambulatory ischemia in patients with chronic stable angina pectoris

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第4期83卷 507-514页

作者： Frishman, WH Glasser, S Stone, P Deedwania, PC Johnson, M Fakouhi, TD New York Med Coll Dept Med Valhalla NY 10595 USA Univ S Florida Coll Med Div Clin Pharmacol Tampa FL USA Brigham & Womens Hosp Div Cardiovasc Boston MA 02115 USA VA Med Ctr Div Cardiol Fresno CA USA Pharmanet Princeton NJ USA GD Searle & Co Skokie IL 60077 USA

This multicenter, randomized, double-blind, parallel group, placebo lead-in, placebo-controlled study compared the antianginal and anti-ischemic effects of once-daily bedtime dosing of controlled-onset extended-release (COER-24) verapamil to a once-daily morning dosing of amlodipine +/- atenolol in patients with chronic stable angina. A total of 551 patients with exercise-induced myocardial ischemia and evidence of coronary artery disease were randomized to a 4-week, forced-dose titration treatment period with (1) COER-24 verapamil 240 mg titrated to 480 mg at bedtime (n = 173), (2) amlodipine 5 mg titrated to 10 mg/day (n = 149), (3) amlodipine 5 mg (titrated to 10 mg) plus atenolol 50 mg/day in the A.M. (n = 154), or (4) placebo (n = 75), Treadmill exercise tolerance testing (standard Bruce protocol), and 48-hour ambulatory electrocardiographic (Holter) monitoring were performed at the end of placebo lead-in and double-blind treatment. Each active treatment significantly improved symptom-limited exercise duration and time to moderate angina (p less than or equal to 0.01 vs placebo). For patients with baseline ischemia, amlodipine resulted in a statistically significant increase in total duration of ischemic episodes compared with placebo, whereas COER-24 verapamil and amlodipine plus atenolol resulted in statistically significant decreases compared with placebo and amlodipine. Heart rate at onset of ischemic episodes and ST product were also significantly increased with amlodipine (p <0.05) compared with either COER-24 or amlodipine plus atenolol, COER-24 and amlodipine alone or in combination with atenolol improved exercise capacity in patients with angina pectoris, COER-24 verapamil monotherapy or amlodipine plus atenolol combination therapy were more effective than amlodipine monotherapy in decreasing ambulatory myocardial ischemia, especially during the hours of 6 A.M. to 12 noon. (C) 1999 by Excerpta Medica, Inc.

关键词：肾上腺素能β受体拮抗剂/治疗应用氨氯地平/治疗应用心绞痛/药物疗法阿替洛尔/治疗应用钙通道阻滞药/投药和剂量钙通道阻滞药/治疗应用慢性病双盲法药物疗法联合心电描记术便携式运动试验治疗结果维拉帕米/投药和剂量维拉帕米/治疗应用老年人老年人 80以上女(雌)性人类男(雄)性中年人

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Safety of control led-onset extended-release verapamil in middle-aged and older patients with hypertension and coronary artery disease

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AMERICAN HEART JOURNAL 2001年第6期142卷 1010-1015页

作者： White, WB Johnson, MF Anders, RJ Elliott, WJ Black, HR Univ Connecticut Ctr Hlth Sect Hypertens & Clin Pharmacol Sch Med Farmington CT 06030 USA Pharmanet Div Biostat Princeton NJ USA Pharmacia Dept Clin Res Skokie IL USA Rush Presbyterian St Lukes Med Ctr Dept Prevent Med Chicago IL 60612 USA

Background Our purpose was to study the safety of controlled-onset, extended-release (COER) verapamil in patients with hypertension or coronary artery disease, with a focus on elderly patients. Methods Adverse event data were pooled from 7 double-blind, multicenter, randomized trials including 1999 patients with hypertension or chronic stable angina pectoris. There were 1042 patients who received COER verapamil 180 to 540 mg once daily in the evening for up to 10 weeks, 373 patients who received placebo, and 584 who received an active comparator agent. Data were analyzed according to the following groups: all patients, patients with hypertension, patients with angina, older patients (greater than or equal to 65 years old), and younger patients (<65 years old). Adverse event rates were compared across the treatment groups by the Fisher exact test. Results In all patients combined, the incidence of constipation (13% vs 2%), dizziness (6% vs 2%), and back pain (3% vs 1%) was higher in patients treated with COER verapamil than with placebo. Patients with hypertension had more back pain (4% vs 1%) and constipation (12% vs 1%) with COER verapamil than with placebo, whereas patients with angina had more bradycardia (2.6% vs 0%), dizziness (8% vs 2%), and constipation (15% vs 3%). Older patients treated with COER verapamil had more bradycardia, constipation, dizziness, and fatigue and had fewer headaches compared with younger patients treated with COER verapamil. Second- or third-degree atrioventricular block was not observed after administration.. of COER verapamil in any subgroup. Conclusion These data demonstrate that COER verapamil has an acceptable safety profile that is largely unrelated to age in patients with hypertension or coronary artery disease.

关键词：心绞痛/药物疗法背痛/化学诱导便秘/化学诱导便秘/预防和控制迟效制剂头晕/化学诱导高血压/药物疗法维拉帕米/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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In vitro investigation of ionic polysaccharide microspheres for simultaneous delivery of chemosensitizer and antineoplastic agent to multidrug-resistant cells

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JOURNAL OF PHARMACEUTICAL SCIENCES 1999年第4期88卷 412-418页

作者： Liu, Z Wu, XY Bendayan, R Univ Toronto Fac Pharm Toronto ON M5S 2S2 Canada

Insufficient intratumoral concentration of therapeutic agents and multidrug resistance are major factors responsible for failure of treatment of solid tumors. Simultaneous delivery of chemosensitizing and antineoplastic agents by microspheres could lead to enhanced chemotherapy of multidrug-resistant (MDR) tumors. Ionic polysaccharide microspheres derived from dextran were used to load chemosensitizers (e.g., verapamil) and anticancer drugs such as vinblastine. High drug loading was achieved for both a single agent and dual agents. The equilibrium drug loading was dependent on the ratio of the microspheres (MS) to the drug, as well as the relative affinity of the agents to the MS in the case of dual agents. The drug release from drug-MS involved hydration and swelling of the MS in addition to ion exchange. The effectiveness of MS-delivered chemosensitizers in the reversal of drug resistance was evaluated by measuring the uptake of [H-3]vinblastine by MDR cells (CH(R)C5). The concomitant delivery of verapamil with vinblastine by the MS led to a 6-7-fold increase in the uptake of vinblastine, a level similar to the uptake obtained with free drug solutions. The results suggest that the antineoplastic and chemosensitizing agents were released effectively from the MS and the bioactivity of the chemosensitizer was preserved during the process.

关键词：佐剂药物/投药和剂量佐剂药物/药理学抗肿瘤药/投药和剂量抗肿瘤药/药理学抗肿瘤药植物/投药和剂量抗肿瘤药植物/药理学 CHO细胞钙通道阻滞药/投药和剂量钙通道阻滞药/药理学细胞存活/药物作用色谱法高压液相仓鼠亚科右旋糖酐类药物释放系统抗药性多药/遗传学基因 MDR 动力学微球体多糖类/化学分光光度法紫外线维拉帕米/投药和剂量维拉帕米/药理学长春碱/投药和剂量长春碱/药理学动物

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EFFECTS OF INTRAVENOUS VERAPAMIL ON CARDIAC-ARRHYTHMIAS AND ON ELECTROCARDIOGRAM

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AMERICAN HEART JOURNAL 1975年第4期90卷 487-498页

作者： HENG, MK SINGH, BN ROCHE, AHG NORRIS, RM MERCER, CJ GREEN LANE HOSP DEPT CARDIOL AUCKLAND NEW ZEALAND GREEN LANE HOSP DEPT CORONARY CARE AUCKLAND NEW ZEALAND AUCKLAND UNIV SCH MED DEPT MED AUCKLAND NEW ZEALAND

The effects of intravenous verapamil on the electrocardiogram in 15 patients with heart disease in sinus rhythm and in 44 patients with supraventricular and ventricular tachyarrhythmias were evaluated. Verapamil prolonged the P-R interval without effect on the QRS duration or the Q-Tc interval. In patients with atrial flutter and fibrillation, A-V block was increased, with slowing of the ventricular rate, in almost all cases but sinus rhythm was restored in only 1 of 12 patients in atrial fibrillation and in 2 of the 11 patients with flutter. Verapamil had no effect in 3 patients with atrial fibrillation complicating WPW syndrome; in 1 of 5 patients with ventricular tachycardia it caused reversion to sinus rhythm. Sinus rhythm was restored promptly by verapamil in 13 of 17 patients with paroxysmal supraventricular tachycardias; in 2 others, sinus rhythm became established 1 to 2 hours after administration of the drug. Transient hypotension, not requiring treatment, was the only side effect noted but not in the patients with supraventricular tachycardias, in whom blood pressure generally increased after reversion to sinus rhythm by verapamil.

关键词：心房颤动/药物疗法心房扑动/药物疗法血压/药物作用心电描记术注射静脉内心动过速/药物疗法维拉帕米/投药和剂量维拉帕米/药理学维拉帕米/治疗应用 Wolff-Parkinson-White综合征/药物疗法青少年成年人老年人儿童儿童学龄前女(雌)性人类男(雄)性中年人

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Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第4期36卷 1233-1238页

作者： Kneale, BJ Chowienczyk, PJ Brett, SE Coltart, DJ Ritter, JM Kings Coll London Ctr Cardiovasc Biol & Med Dept Clin Pharmacol London WC2R 2LS England Kings Coll London Ctr Cardiovasc Biol & Med Dept Cardiol London WC2R 2LS England

OBJECTIVES The goal of this study was to investigate the mechanism of reduced vasoconstrictor sensitivity to norepinephrine in women compared with men. BACKGROUND beta(2)-adrenergic agonists such as albuterol dilate forearm resistance vessels, partly by activating the alpha-arginine/nitric oxide pathway. Norepinephrine (which acts as beta- as well. as alpha-adrenergic receptors) causes less forearm vasoconstriction in women than it does in men. This could be explained by a greater sensitivity to beta(2)-recepror stimulation in women than in men. METHODS Forearm blood flow was measured by venous occlusion plethysmography in healthy women (days 10 to 14 of the menstrual cycle) and in men. Drugs were administered via the brachial artery in three separate protocols: albuterol +/- N(G)-monomethyl-L-arginine tan inhibitor of nitric oxide synthase);substance P, nitroprusside and verapamil (control vasodilators);norepinephrine (+/- propranolol, a beta-adrenergic receptor antagonist). RESULTS Vasodilator responses to albuterol were greater in women than they were in men (p = 0.02 by analysis of variance). N(G)-monomethyl-L-arginine reduced these similarly in men and women. Responses to control vasodilators were less in women than they were in men teach p < 0.05). Norepinephrine caused less vasoconstriction in women than it did in men (p = 0.02). Propranolol did not influence basal flow in either gender nor responses of men to norepinephrine but increased vasoconstriction to each dose of norepinephrine in women (p < 0.0001 for interaction between gender and propranolol). Responses to norepinephrine coinfused with propranolol were similar in men and women. CONCLUSIONS Stimulation of beta(2)-adrenergic receptors causes greater forearm vasodilation in premenopausal women, at midmenstrual cycle, than it does in men. This is sufficient to explain why vasoconstriction to brachial artery norepinephrine is attenuated in such women. (J Am Coil Cardiol 2000;36:1233-8) (C) 2000 by the A

关键词：肾上腺素能α激动剂/投药和剂量肾上腺素能β激动剂/投药和剂量肾上腺素能β受体拮抗剂/投药和剂量沙丁胺醇/投药和剂量血流速度/药物作用肱动脉/药物作用肱动脉/生理学酶抑制剂/投药和剂量前臂/血液供给注射动脉内一氧化氮合酶/拮抗剂和抑制剂硝普钠/投药和剂量去甲肾上腺素/投药和剂量体积描记术普萘洛尔/投药和剂量受体肾上腺素能β2/药物作用参考值性征 P物质/投药和剂量血管阻力/药物作用血管阻力/生理学血管舒张/药物作用血管舒张药/投药和剂量维拉帕米/投药和剂量 ωN-甲基精氨酸/投药和剂量成年人女(雌)性人类男(雄)性

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ELECTROPHYSIOLOGY AND PHARMACOLOGY OF CARDIAC-ARRHYTHMIAS .6. CARDIAC EFFECTS OF VERAPAMIL

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AMERICAN HEART JOURNAL 1975年第5期89卷 665-673页

作者： ROSEN, MR WIT, AL HOFFMAN, BF COLUMBIA UNIV COLL PHYS & SURG DEPT PHARMACOL 630 W 168TH ST NEW YORK NY 10032 USA

It is clear from clinical and experimental data that have been reported thus far that verapamil is highly effective in the therapy of cardiac arrhythmias, and that it acts by a different mechanism than most of the commonly used antiarrhythmic drugs. The available clinical data indicate that on intravenous administration verapamil is as good as and perhaps superior to quinidine, procainamide and propranolol for the therapy of many atrial arrhythmias. Unfortunately the extent to which it is useful as longterm prophylaxis has not yet been reported, nor has its toxicity during protracted oral administration. The effects of verapamil on cardiac action potentials clearly indicate that it modifies the slow response to a much greater extent than the fast response. Studies of cardiac tissues from diseased human atria have indicated that slow response action potentials occur frequently. 31 It is possible that such action potentials are responsible for the reentrant and automatic arrhythmias which occur in association with clinical cardiac disease. Whether the efficacy of verapamil in the therapy of atrial arrhythmias is primarily due to abolishing slow response activity in diseased atrial tissues or to suppression of propagation through the atrioventricular node is uncertain. However, it is likely that the therapeutic action of the drug may result from altered propagation of an arrhythmia through the atrioventricular junction as well as from the effects of the drug on diseased atrial and ventricular tissues.

关键词：动作电位/药物作用投药口服心房颤动/药物疗法心房扑动/药物疗法房室结/药物作用钙/代谢心脏传导系统/药物作用注射静脉内心肌/代谢浦肯野纤维/药物作用窦房结/药物作用心动过速/药物疗法心动过速阵发性/药物疗法维拉帕米/投药和剂量维拉帕米/治疗应用动物人类

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Effect of verapamil on QT interval dynamicity

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第5期83卷 807-808页

作者： Fauchier, L Babuty, D Poret, P Autret, ML Cosnay, P Fauchier, JP CHU Trousseau Serv Cardiol B F-37044 Tours France CHU Trousseau Lab Electrophysiol Cardia F-37044 Tours France

Using measurements of QT/RR slopes with a computerized Holter system, QT interval dynamicity was evaluated in 19 patients with normal structural heart before and 2 months after oral treatment with verapamil prescribed for paroxysmal atrioventricular nodal reentrant tachycardia. Verapamil significantly shortened QT at low heart rates, mainly in the diurnal period, and this characteristic may explain, in part, the previously reported protective effect of verapamil against torsades de pointes. [ABSTRACT FROM AUTHOR]

关键词：投药口服抗心律失常药/投药和剂量抗心律失常药/治疗应用昼夜节律心电描记术便携式/药物作用心率/药物作用心动过速房室结折返性/药物疗法心动过速阵发性/药物疗法扭转性室速/药物疗法维拉帕米/投药和剂量维拉帕米/治疗应用成年人老年人女(雌)性人类男(雄)性中年人

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Familial polymorphic ventricular arrhythmias - A quarter century of successful medical treatment based on serial exercise-pharmacologic testing

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第7期34卷 2015-2022页

作者： Fisher, JD Krikler, D Hallidie-Smith, KA Hammersmith Hosp Royal Postgrad Med Sch Div Cardiovasc Dis London England

OBJECTIVES We sought to determine whether objective tests of antiarrhythmic drug efficacy could produce favorable short- and long-term outcomes in a family with idiopathic malignant ventricular arrhythmias. BACKGROUND In 1973 a family presented with a history of several generations of syncopal spells and sudden death. Some individuals had nonspecific electrocardiographic (ECG) changes. Their QT intervals were normal at rest and with exercise. Autopsies in two young family members showed no cardiac abnormalities, specifically no evidence of arrhythmogenic right ventricular dysplasia, other cardiomyopathy, myocarditis or gross abnormality of the conduction system. METHODS Available family members had screening ECGs. Symptomatic members had a battery of tests, including electrophysiologic studies, ambulatory ECGs, audiograms, exercise stress testing, serum catecholamine levels during rest and exercise and isoproterenol infusion. Serial exercise-pharmacologic testing was performed in symptomatic family members until induction of an arrhythmia during exercise required higher work loads or became impossible. RESULTS Arrhythmias were not induced during electrophysiologic studies. In several family members tested, ventricular premature beats and then rapid polymorphic ventricular arrhythmias occurred whenever the sinus rate exceeded 130 beats/min. Emotional stress, isoproterenol infusion and exercise all elicited similar arrhythmias. Catecholamine levels during exercise were, however, unequivocally normal in two of three family members tested. Beta-blockers appeared to be the most effective pharmacologic agent for prevention of these arrhythmias. The efficacy of treatment has been confirmed during a follow-up of 25 years. CONCLUSIONS This family appears to have catecholamine hypersensitivity as the basis for their ventricular arrhythmias. Guided therapy using serial exercise-pharmacologic testing provided reliable protection for this familial ventricular arrhythmia during a

关键词：肾上腺素能β激动剂肾上腺素能β受体拮抗剂/投药和剂量肾上腺素能β受体拮抗剂/治疗应用抗心律失常药/投药和剂量抗心律失常药/治疗应用抗惊厥药/投药和剂量抗惊厥药/治疗应用儿茶酚胺类/血液投药途径超声心动描记术心电描记术便携式运动试验随访研究心室/诊断显像心室/病理学异丙肾上腺素系谱苯妥英/投药和剂量苯妥英/治疗应用普萘洛尔/投药和剂量普萘洛尔/治疗应用回顾性研究心动过速室性/血液心动过速室性/诊断心动过速室性/药物疗法心动过速室性/遗传学治疗结果维拉帕米/投药和剂量维拉帕米/治疗应用青少年成年人儿童女(雌)性人类男(雄)性中年人

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No-reflow is an independent predictor of death and myocardial infarction after percutaneous coronary intervention

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AMERICAN HEART JOURNAL 2003年第1期145卷 42-46页

作者： Resnic, FS Wainstein, M Lee, MKY Behrendt, D Wainstein, RV Ohno-Machado, L Kirshenbaum, JM Rogers, CDK Popma, JJ Piana, R Vanderbilt Univ Sch Med Div Cardiol Nashville TN 37212 USA Brigham & Womens Hosp Div Cardiol Decis Syst Grp Boston MA 02116 USA Brigham & Womens Hosp Div Cardiovasc Med Boston MA 02116 USA

Background No-reflow occurring during percutaneous coronary intervention (PCI) has been associated with poor inhospital outcomes. The objectives of this analysis were to evaluate the occurrence of no-reflow as an independent predictor of adverse events and to determine whether treatment with intracoronary vasodilator therapy affected clinical outcomes. Methods We prospectively collected data from 4264 consecutive patients undergoing PCI, identifying those with no-reflow, and analyzed their treatments and clinical outcomes. Results No-reflow was identified in 135 of 4264 patients (3.2%). Baseline demographics were comparable, but patients with no-reflow were more likely to have acute myocardial infarction, unstable angina, and cardiogenic shock and to have undergone saphenous vein graft interventions. No-reflow was highly predictive of postprocedural myocardial infarction (17.7% vs 3.5% in patients without no-reflow, P < .001) and death (7.4% vs 2.0%, P < .001) and remained a strong independent predictor of death or myocardial infarction after multivariate analysis (odds ratio 3.6, P < .001). The administration of intracoronary verapamil, sodium nitroprusside, or both was not associated with a reduction in the rate of death or myocardial infarction (adjusted odds ratio of death or myocardial infarction 1.04, P = .945 for nitroprusside,and adjusted odds ratio of death or myocardial infarction 0.94, P = .91 for verapamil), despite an improvement in angiographic flow rates for patients treated with sodium nitroprusside. Conclusions No-reflow is a strong independent predictor of inhospital mortality and postprocedural myocardial infarction. Administration of verapamil or sodium nitroprusside was not associated with improved inhospital outcomes in patients with no-reflow, although anterograde flow rates were improved in patients treated with sodium nitroprusside.

关键词：病例对照研究死亡原因冠状血管造影术冠状动脉循环心肌梗死/死亡率心肌梗死/病理生理学心肌梗死/放射摄影术心肌梗死/治疗硝普钠/投药和剂量比值比试验预期值前瞻性研究回顾性研究危险因素血管舒张药/投药和剂量维拉帕米/投药和剂量女(雌)性人类男(雄)性中年人

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