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新型正性肌力药物OPC-8212对严重充血性心力衰竭的急性血流动力学效应

Acute hemodynamic effects of a new inotropic agent, OPC-8212, on severe congestive heart failure.

作者信息

Sasayama S, Inoue M, Asanoi H, Kodama K, Hori M, Sakurai T, Kawai C

出版信息

Heart Vessels. 1986;2(1):23-8. doi: 10.1007/BF02060240.

DOI:10.1007/BF02060240
PMID:3722083
Abstract

The hemodynamic and clinical effects of OPC-8212, a newly synthesized, orally effective inotropic agent, were assessed for the first time in ten patients with severe congestive heart failure by means of right heart catheterization with a Swan-Ganz catheter. Cardiac output was determined by the thermodilution technique. Patients received a single oral dose of 6 mg/kg. To determine the magnitude and time-course of the effects of OPC-8212, measurements were made during an observation period before and 2, 4, 8, and 12 h after administration. Blood was also taken at these times for measurement of the concentration of plasma OPC-8212. No large meals were allowed during the first 4 h. After the single oral dose of OPC-8212, plasma concentrations increased rapidly, reaching an effective level after 8 h and peaking at 12 h. Hemodynamic performance improved as the mean OPC-8212 plasma level increased, with the maximum effect being observed between 8 and 12 h after acute administration of the drug. At 8 h, the cardiac index was increased from the baseline value of 2.4 +/- 0.2 (SEM) to 2.8 +/- 0.3 1/min/m2 (P less than 0.01). The stroke work index rose from 26.2 +/- 5.1 to 31.7 +/- 60 g . m/m2. The excessive pulmonary artery diastolic pressure fell from 22 +/- 2 to 17 +/- 3 mmHg at 8 h (P less than 0.001) and to 16 +/- 2 mmHg (P less than 0.001) at 12 h. The incidence of ventricular premature beats was not increased and no other side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

首次通过使用Swan-Ganz导管进行右心导管插入术,对10例严重充血性心力衰竭患者评估了新合成的口服有效强心剂OPC-8212的血流动力学和临床效果。心输出量通过热稀释技术测定。患者接受6mg/kg的单次口服剂量。为了确定OPC-8212作用的程度和时间过程,在给药前以及给药后2、4、8和12小时的观察期内进行测量。还在这些时间采集血样以测量血浆OPC-8212的浓度。在最初4小时内不允许进食大餐。单次口服OPC-8212后,血浆浓度迅速升高,8小时后达到有效水平,并在12小时达到峰值。随着血浆OPC-8212平均水平的升高,血流动力学性能得到改善,在急性给药后8至12小时观察到最大效果。在8小时时,心脏指数从基线值2.4±0.2(标准误)增加到2.8±0.3 1/min/m²(P<0.01)。每搏功指数从26.2±5.1增加到31.7±6.0 g·m/m²。过高的肺动脉舒张压在8小时时从22±2降至17±3 mmHg(P<0.001),在12小时时降至16±2 mmHg(P<0.001)。室性早搏的发生率没有增加,也未观察到其他副作用。(摘要截断于250字)

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本文引用的文献

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Problems in assessment of new pharmacologic agents for the heart failure patient.
Am Heart J. 1981 Sep;102(3 Pt 2):584-90. doi: 10.1016/0002-8703(81)90748-1.
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Evaluating the efficacy of new inotropic agents.评估新型正性肌力药物的疗效。
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口服OPC-8212治疗充血性心力衰竭:血流动力学改善及运动能力增强。
Heart Vessels. 1986;2(3):166-71. doi: 10.1007/BF02128143.
4
A new cardiotonic agent, OPC-8212, elevates the myocardial oxygen consumption versus pressure-volume area (PVA) relation in a similar manner to catecholamines and calcium in canine hearts.一种新型强心剂OPC - 8212,以与儿茶酚胺和钙类似的方式提高犬心脏中与压力-容积面积(PVA)相关的心肌耗氧量。
Heart Vessels. 1988;4(3):153-61. doi: 10.1007/BF02058428.
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OPC-8212 in the treatment of congestive heart failure: results of a pilot study.OPC-8212治疗充血性心力衰竭:一项初步研究的结果
Cardiovasc Drugs Ther. 1988 Dec;2(5):653-60. doi: 10.1007/BF00054205.
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A multicenter study of a new inotropic agent, piperanometozine (OPC-8212) in congestive heart failure: clinical improvement during short-term treatment.一种新型强心剂哌拉诺美嗪(OPC-8212)治疗充血性心力衰竭的多中心研究:短期治疗期间的临床改善情况
Cardiovasc Drugs Ther. 1987 Aug;1(2):169-75. doi: 10.1007/BF02125470.
7
A placebo-controlled, randomized, double-blind study of OPC-8212 in patients with mild chronic heart failure. OPC-8212 Multicenter Research Group.OPC-8212治疗轻度慢性心力衰竭患者的安慰剂对照、随机、双盲研究。OPC-8212多中心研究组
Cardiovasc Drugs Ther. 1990 Apr;4(2):419-25. doi: 10.1007/BF01857748.
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Effects of a new 1,3-thiazole derivative ZSY-39 on force of contraction and cyclic AMP content in canine ventricular muscle.
Cardiovasc Drugs Ther. 1990 Aug;4(4):1127-34. doi: 10.1007/BF01856509.
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Effect of OPC-8490 on the membrane potentials and membrane currents of single guinea-pig myocytes.
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Subcellular mechanism of the positive inotropic effect of a new quinolinone derivative OPC-8490 on the dog ventricular myocardium.
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Electro-mechanical effects of 3, 4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-qu inolinone (OPC-8212), a new positive inotropic agent. Isolated adult canine Purkinje strands and ventricular trabeculae.
Arzneimittelforschung. 1984;34(3A):371-5.
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Effects of a new positive inotropic agent, 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212) and its solvent sulfolane on isolated heart preparations of the rat, guinea pig, and dog.一种新型正性肌力药物3,4-二氢-6-[4-(3,4-二甲氧基苯甲酰基)-1-哌嗪基]-2(1H)-喹啉酮(OPC-8212)及其溶剂环丁砜对大鼠、豚鼠和犬离体心脏标本的影响。
Arzneimittelforschung. 1984;34(3A):359-63.
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Effects of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl] -2(1H)-quinolinone (OPC-8212), a new inotropic agent, on cardiotonic activity and coronary hemodynamics.新型强心剂3,4-二氢-6-[4-(3,4-二甲氧基苯甲酰基)-1-哌嗪基]-2(1H)-喹啉酮(OPC-8212)对强心活性和冠状动脉血流动力学的影响。
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Chem Pharm Bull (Tokyo). 1984 Jun;32(6):2100-10. doi: 10.1248/cpb.32.2100.