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Impaired cholera toxin relaxation with age in rat aorta

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES 1999年第4期54卷 B154-B159页

作者： Chapman, J Schutzer, WE Watts, VJ Mader, SL Vet Adm Med Ctr Portland OR 97207 USA Oregon Hlth Sci Univ Dept Med & Pharmacol Portland OR 97201 USA

Beta-adrenergic-mediated vasorelaxation declines with maturation and aging. Available data suggest that impaired stimulatory G-protein function could explain this deficit. We have previously found a lass of cholera toxin (CT)-stimulated adenosine diphosphate (ADP) ribosylation with age in rat aortic membrane preparations, without evidence for loss of the stimulatory alpha subunit of G protein (Gs alpha) by immunoblotting. The purpose of this investigation was to determine if cholera toxin-mediated vasorelaxation was also impaired with age. Aortic ring segments from 6 weeks, 6 months, 12 months, and 24 months old male F-344 rats were used. Contraction to KCl and phenylephrine was assessed along with relaxation to cholera toxin (azide-free), isoproterenol, and forskolin. There were no age-related changes to KC? or phenylephrine contraction. There xas a significant decrease with age in relaxation to isoproterenol. This loss with age was significantly greater with KCl-preconstricted vessels than phenylephrine-preconstricted vessels. There were no age-related changes in the relaxation to forskolin. There was a significant decrease with age in the maximal relaxation to cholera toxin as well as a rightward shift in the dose-response curve. Cholera toxin-stimulated adenosine 3',5'-cyclic phospate (cAMP) levels were measured and there Has no increase in cAMP levels surrounding the time period associated with relaxation induced by cholera toxin. These data suggest that different preconstricting agents markedly affect the age-related changes in beta-adrenergic-mediated vasorelaxation. Furthermore, they suggest that the mechanism of cholera toxin-mediated vasorelaxation may not be mediated through increases in cAMP concentration.

关键词：腺苷二磷酸/代谢肾上腺素能β激动剂/投药和剂量肾上腺素能β激动剂/药理学衰老/生理学主动脉胸/药物作用霍乱毒素/投药和剂量霍乱毒素/药理学环AMP/代谢剂量效应关系药物福司柯林/投药和剂量福司柯林/药理学 GTP结合蛋白质类/生理学异丙肾上腺素/投药和剂量异丙肾上腺素/药理学苯福林/投药和剂量苯福林/药理学氯化钾/投药和剂量氯化钾/药理学大鼠近交F344 血管收缩药/投药和剂量血管收缩药/药理学血管舒张药/投药和剂量血管舒张药/药理学动物男(雄)性大鼠

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Tailored therapy using dobutamine and nitroglycerin in advanced heart failure

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第8期84卷 941-+页

作者： Drazner, MH Solomon, MA Thompson, B Yancy, CW Univ Texas SW Med Ctr Div Cardiol Dallas TX 75235 USA St Paul Med Ctr Dallas TX USA

In 29 patients with advanced heart failure, therapy tailored to hemodynamic goals was attempted using an initial infusion of dobutamine and nitroglycerin (the latter in those with pulmonary hypertension) followed by escalating doses of oral vasodilators. In the 23 patients who were weaned from inodilator therapy, significant improvements in hemodynamic parameters and a low 90-day hospital readmission rate were documented.

关键词：血管紧张素转换酶抑制药/投药和剂量强心药/投药和剂量强心药/治疗应用多巴酚丁胺/投药和剂量多巴酚丁胺/治疗应用高血压肺性/药物疗法高血压肺性/病因学输注静脉内输注胃肠外异山梨酯硝酸/投药和剂量硝酸甘油/投药和剂量硝酸甘油/治疗应用回顾性研究治疗结果血管舒张药/投药和剂量血管舒张药/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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Preliminary thermographic evaluation of new nitroglycerine tape on the peripheral circulatory disturbance in systemic sclerosis

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ANNALS OF THE RHEUMATIC DISEASES 2002年第2期61卷 177-179页

作者： Kan, C Akimoto, S Abe, M Okada, K Ishikawa, O Gunma Univ Sch Med Dept Dermatol Maebashi Gumma 3718511 Japan

Objective: To evaluate the effects of newly developed nitroglycerine (NTG) tape on the peripheral circulatory disturbance in systemic sclerosis (SSc). Methods: The finger temperature (FT) of 25 patients with SSc was monitored by thermography before the application of NTG tape to the wrist and one hour afterwards. To check the placebo effect, the change of FT with placebo tape in six patients who had shown a distinct rise in FT (>2degreesC) with NTG tape was monitored. Results: Twenty one patients with SSc had a low FT before the application of NTG tape (colder than mean-2SD of normal controls). FT was significantly raised in patients with SSc after the application of NTG tape (p<0.01). Patients with low FT showed a distinct rise in FT more often than patients with a normal FT (71% v 0%, p<0.01). FT was raised with NTG tape more than with placebo tape (4.2 (SD 1.9)degreesC v 2.2 (2.8)degreesC, p<0.05). Conclusion: The application of NTG tape increases peripheral circulation in patients with SSc who have distinct circulatory disturbance. The application of NTG tape may improve peripheral circulatory disturbance in SSc.

关键词：投药皮肤病例对照研究药物释放系统指/血液供给硝酸甘油/投药和剂量外周血管疾病/药物疗法外周血管疾病/病因学硬皮病系统性/并发症硬皮病系统性/药物疗法温度记录法血管舒张药/投药和剂量成年人老年人女(雌)性人类男(雄)性中年人

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Hemodynamic and electrophysiologic effects of acute chocolate ingestion in young adults

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第3期84卷 370-+页

作者： Baron, AM Donnerstein, RL Samson, RA Baron, JA Padnick, JN Goldberg, SJ Univ Arizona Coll Med Ctr Heart Tucson AZ 85724 USA Steele Mem Childrens Res Ctr Dept Pediat Diamond Res Lab Tucson AZ USA

The purpose of this study was to determine the hemodynamic and electrophysiologic effects of acute chocolate, and hence theobromine, ingestion on the hearts of young adults. Theobromine was not found to have any cardi... 详细信息

关键词：可可树交叉研究双盲法超声心动描记术多普勒心电描记术/药物作用心脏传导系统/药物作用可可碱/投药和剂量可可碱/药理学血管舒张药/投药和剂量血管舒张药/药理学成年人女(雌)性人类男(雄)性

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Dipyridamole administration at the end of an insufficient exercise Tc-99m MIBI SPECT improves detection of multivessel coronary artery disease in patients with previous myocardial infarction

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第5期85卷 532-535页

作者： Candell-Riera, J Santana-Boado, C Castell-Conesa, J Aguadé-Bruix, S Bermejo-Fraile, B Soler-Soler, J Hosp Gen Univ Vall dHebron Serv Cardiol Barcelona 08035 Spain Hosp Gen Univ Vall dHebron Nucl Med Serv Barcelona 08035 Spain Hosp Gen Univ Vall dHebron Serv Med Preventiva Barcelona 08035 Spain

To demonstrate that the administration of dipyridamole at the end of an insufficient maximal subjective exercise test can improve the diagnostic accuracy of single-photon emission computed tomography in patients with previous myocardial infarction, 209 consecutive patients were studied with technetium-99m methoxyisobutyl isonitrile single-photon emission computed tomography and coronary angiography, Patients were divided in 3 groups: group 1, 107 patients with sufficient exercise testing;group 2, 55 patients with insufficient exercise testing;group 3, 47 patients with insufficient exercise testing in whom intravenous dipyridamole (0.56 mg/kg aver 4 minutes) was administered at the end of exercise. In groups 1 and 3 the sensitivity values for the diagnosis of multivessel disease were significantly higher (80% and 76%, respectively) than those in group 2 (59% [p = 0.009 and p = 0.02, respectively]). Specificity and predictive values were not different among the 3 groups. Thus, in patients with previous infarction in whom adequate levels of exercise could not be achieved, dipyridamole administration at the end of exercise significantly increased the sensitivity for diagnosing multivessel disease. (C)2000 by Excerpta Medica, Inc.

关键词：病例对照研究冠心病/并发症冠心病/流行病学冠心病/放射性核素显像双嘧达莫/投药和剂量双嘧达莫/诊断应用运动试验心脏导管插入术心肌梗死/并发症试验预期值前瞻性研究放射性药物/诊断应用敏感性与特异性 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/诊断应用女(雌)性人类男(雄)性中年人

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Visual compatibility of sodium nitroprusside with other injectable medications given to pediatric patients

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AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY 2001年第15期58卷 1422-1426页

作者： Seto, W Trope, A Carfrae, L Walker, S Hosp Sick Children Dept Pharm Crit Care Unit Toronto ON M5G 1X8 Canada Moncton Hosp SE Hlth Care Corp Neurosurg Intens Care Unit New Brunswick NJ USA Sunnybrook & Womens Coll Hlth Sci Ctr Dept Pharm Toronto ON Canada Univ Toronto Fac Pharm Toronto ON Canada

The Notes section welcomes the following types of contributions: (1) practical innovations or solutions to everyday practice problems, (2) substantial updates or elaborations on work previously published by the same authors, (3) important confirmations of research findings previously published by others, and (4) short research reports, including practice surveys, of modest scope or interest. Notes should be submitted with AJHP's manuscript checklist. The text should be concise and the number of references, tables, and figures should be limited.

关键词：胺碘酮/化学心血管疾病/外科学导管插入术中心静脉化学沉淀色复方合剂药物配伍禁忌氢离子浓度/药物作用输注静脉内硝普钠/投药和剂量硝普钠/化学药用溶液/化学手术后医护普罗帕酮/化学血管舒张药/投药和剂量血管舒张药/化学儿童人类

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Dypiridamole, a cGMP phosphodiesterase inhibitor, transiently improves the response to inhaled nitric oxide in two newborns with congenital diaphragmatic hernia

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INTENSIVE CARE MEDICINE 1999年第3期25卷 300-303页

作者： Thébaud, B Saizou, C Farnoux, C Hartman, JF Mercier, JC Univ Paris 07 Fac Med Xavier Bichat Hop Robert Debre Serv Pediat Reanimat F-75019 Paris France

Introduction: Congenital diaphragmatic hernia (CDH) remains a frusta;ling cause of respiratory failure associated with persistent pulmonary hypertension of the newborn (PPHN). Although inhaled nitric oxide (iNO) is effective in many infants with PPHN, it often fails to improve oxygenation in infants with CDH. As the increase in vascular smooth muscle cyclic guanosine monophosphate (cGMP) in response to iNO may be impeded by increased phosphodiesterase type-V (PDE-V) activity, it has been suggested that: PDE-V blockade potentiates the efficiency of iNO. Case reports: We used dypiridamole (Persantine), a specific PDE-V inhibitor, in two patients with CDH. Prenatal diagnosis showed a left-sided CDH at 23 weeks of gestation (GA) with intrathoracic stomach and left heart underdevelopment in the one infant and a right-sided CDH at 26 weeks GA with intrathoracic liver in the other. After antenatal corticoids, planned delivery was performed by the vaginal route at 38 weeks GA. Preoperative stabilization was achieved by high frequency oscillation, iNO and inotropic support over 24 h. Both had early pneumothorax drained by a chest tube. Despite optimization of ventilatory and hemodynamic support with surfactant replacement, iNO and adrenaline, oxygenation worsened progressively. Dypiridamole was introduced intravenously at 27 and 40 h, respectively, and improved oxygenation over the next 12 h. However, oxygenation again deteriorated and both patients died. Conclusion: Dypiridamole enhanced the response to iNO in PPHN associated with CDH, although this effect was transient. Combined therapy of iNO with PDE-V inhibitors may improve pulmonary vasodilation in some forms of PPHN which do not respond to iNO, thereby reducing the need for extracorporeal membrane oxygenation (ECMO) and improving outcome.

关键词：投药吸入双嘧达莫/药理学致命性结局疝横膈/治疗一氧化氮/投药和剂量一氧化氮/药代动力学氧/代谢磷酸二酯酶抑制剂/药理学血管舒张药/投药和剂量血管舒张药/药代动力学人类婴儿新生

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

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第8期85卷 1007-1011页

作者： Del Rosso, A Bartoletti, A Bartoli, P Ungar, A Bonechi, F Maioli, M Ieri, A Osped San Pietro Igneo Div Cardiol Fucecchio Italy Osped Santa Maria Annunziata Div Cardiol Florence Italy Univ Florence Inst Geriatr & Gerontol Inst Florence Italy

Shortened head-up tilt testing (HUT) potentiated with sublingual nitroglycerin (60 degrees passive standing for 20 minutes followed, if negative, by 400 mu g of sublingual nitroglycerin spray with the test continuing for another 20 minutes) differs from conventional nitroglycerin HUT for a shorter drug-free phase (20 vs. 45 minutes). To compare the positivity rate of the 2 protocols, both tests were performed in a randomized sequence in 10 patients with unexplained syncope (study 1), and another 42 patients were randomly assigned either to conventional or to shortened nitroglycerin HUT (study 2). To evaluate the reproducibility of the shortened nitroglycerin HUT, another 38 patients with unexplained syncope underwent 2 consecutive tests within a 7 +/- 8 day interval (study 3). Finally, to evaluate the specificity of the test, 47 control subjects underwent shortened nitroglycerin HUT (study 4). Seven positive responses were observed during shortened nitroglycerin HUT, and there were 8 positive responses during conventional nitroglycerin HUT (p = NS) in the study 1 group. Fifteen positive (71%) responses, 5 negative responses, and 1 exaggerated response were observed during shortened nitroglycerin HUT;16 positive (76%, p = NS vs shortened nitroglycerin HUT), 3 negative, and 2 exaggerated responses were observed during conventional nitroglycerin HUT in the study 2 group. During the first test, 21 patients (55%) had a positive, 15 patients had a negative, and 2 patients had an exaggerated response in study group 3. During the second test, 15 positive (39%), 19 negative, and 4 exaggerated responses were observed. Thus, the reproducibility was 67% for a positive and 94% far a negative test. In control subjects, 2 positive (4%) responses, 38 negative, and 7 exaggerated responses were observed with a specificity of 96% in study group 4. In patients with unexplained syncope, shortened nitroglycerin HUT allowed a positivity rate similar to that of the conventional test. Moreo

关键词：投药舌下硝酸甘油/投药和剂量硝酸甘油/诊断应用可重复性结果敏感性与特异性晕厥/诊断晕厥/病因学倾斜台试验/方法血管舒张药/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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Persistent primary coronary dilation induced by transatrial delivery of nitroglycerin into the pericardial space: A novel approach for local cardiac drug delivery

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第7期33卷 2073-2077页

作者： Waxman, S Moreno, R Rowe, KA Verrier, RL Beth Israel Deaconess Med Ctr Div Cardiol Boston MA 02215 USA Beth Israel Deaconess Med Ctr Inst Prevent Cardiovasc Dis Boston MA 02215 USA Harvard Univ Sch Med Boston MA USA

OBJECTIVES We compared the effects of intrapericardial and intracoronary nitroglycerin on coronary cross-sectional area as assessed by intravascular ultrasound and demonstrated the feasibility of local cardiac drug delivery by a newly developed method to access the normal pericardial space through the right atrial appendage. BACKGROUND Studies of nitric oxide (NO) donors have suggested that their antiarrhythmic and antiproliferative properties are more effective when administered by the intrapericardial rather than intravascular route. We postulated that NO donors delivered intrapericardially would also cause sustained coronary vasodilation without significant systemic hypotension. METHODS Intrapericardial nitroglycerin (200 mu g) was administered in live Yorkshire pigs. Coronary cross-sectional luminal area was measured with intravascular ultrasound at various time intervals. The effects of intracoronary nitroglycerin on coronary luminal area were used for comparison. RESUTLS Transatrial pericardial access required 1 to 3 min in all animals. Intrapericardial nitroglycerin was associated with a mean 31.7% increase in luminal area at 5 min (p < 0.001). Vasodilation peaked between 5 and 10 min and persisted for 15 min. In contrast, intracoronary nitroglycerin was associated with a smaller mean increase in luminal area (20.3% at 5 min, p < 0.01) that disappeared by 10 min. Significant systemic hypotension was observed at 3 min with intracoronary but not with intrapericardial nitroglycerin. CONCLUSIONS Sustained coronary vasodilation can be achieved with intrapericardial delivery of nitroglycerin without systemic hypotension. Nitric oxide donors with longer half-lives could prove beneficial in the treatment of myocardial ischemic syndromes when administered through this route. Transatrial pericardial access offers a novel route for local cardiac drug delivery. (C) 1999 by the American College of Cardiology.

关键词：血压/药物作用冠状血管/诊断显像冠状血管/药物作用药物释放系统/方法心率/药物作用注射硝酸甘油/投药和剂量心包猪超声检查介入性血管舒张/药物作用血管舒张药/投药和剂量动物女(雌)性男(雄)性

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Effect of atropine on QT prolongation and torsade de pointes induced by intracoronary acetylcholine in the long QT syndrome

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第5期83卷 714-718页

作者： Furushima, H Niwano, S Chinushi, M Yamaura, M Taneda, K Washizuka, T Aizawa, Y Niigata Univ Sch Med Dept Internal Med 1 Niigata 951 Japan

We recently reported a marked QT prolongation and torsade de pointes (TDP) induced by an intracoronary acetylcholine (ACh) administration in patients with long QT syndrome, but the mechanism was not determined. In the present study, the effect of atropine on the ACh-induced QT prolongation and TDP was studied in long QT syndrome. Nine patients with congenital long QT syndrome were studied. ACh at doses of 20, 50, and 100 mu g were injected in a stepwise manner into the left main coronary artery, and the changes in the QT interval were measured. In 4 of the 9 patients, ACh administration at a dose of 100 mu g was repeated after an intravenous atropine administration at a dose of 0.5 mg. The QT intervals were measured using 12-lead electrocardiograms, and the data were compared before and after atropine administration. The coronary angiograms were normal and coronary spasm was not induced by ACh in all patients. The intracoronary administration of ACh at a dose of 100 mu g significantly prolonged the corrected QT interval (QT(c)), from 511 +/- 26 to 629 +/- 40 ms (p <0.05). In 5 of the 9 patients, TDP was induced and was spontaneously terminated within 10 seconds (n = 4) or required direct-current shock (n = 1). After atropine administration, intracoronary ACh at the same dose resulted in no QT prolongation, and the QT(c) interval remained unchanged (525 +/- 29 vs 520 +/- 21 ms before and after atropine), and no TDP was induced. These findings indicate that the muscarinic receptor is involved in ACh-induced QT prolongation and TDP, both of which were prevented by the atropine administration. (C)1999 by Excerpta Medica, Inc.

关键词：乙酰胆碱/投药和剂量乙酰胆碱/诊断应用抗心律失常药/投药和剂量抗心律失常药/治疗应用阿托品/投药和剂量阿托品/治疗应用冠状血管造影术冠状血管电抗休克心电描记术/药物作用注射动脉内注射静脉内 QT延长综合征/先天性 QT延长综合征/病理生理学 QT延长综合征/放射摄影术受体毒蕈碱/药物作用受体毒蕈碱/生理学扭转性室速/化学诱导扭转性室速/预防和控制扭转性室速/治疗血管舒张药/投药和剂量血管舒张药/诊断应用青少年成年人老年人女(雌)性人类男(雄)性中年人

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