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静脉注射依诺昔酮的急性血流动力学反应:一项动物研究及心脏手术后婴儿的初步报告。

Acute hemodynamic response to intravenous enoximone: an animal study and preliminary report in infants after cardiac surgery.

作者信息

Schranz D, Huth R, Dahm M, Iversen S, Hein E, Stopfkuchen H, Jüngst B K

机构信息

Department of Pediatrics, University Mainz, F.R.G.

出版信息

J Cardiovasc Pharmacol. 1989;14 Suppl 1:S62-8.

PMID:2480488
Abstract

In light of previous studies in adults, we considered that enoximone could be useful in treating children with therapy-resistant cardiovascular insufficiency. Prior to clinical administration, we investigated the cardiovascular properties of enoximone in anesthetized and ventilated piglets characterized by small stroke volume and high heart rate. Enoximone was administered intravenously in increasing doses (0.25, 0.5, and 1 mg/kg). The animals were monitored with heart rate, systemic and pulmonary arterial pressures, and continuous electromagnetic flow. Enoximone induced a dose-dependent flow increase, whereby heart rate and systemic arterial pressure changed only slightly. With regard to persistent pulmonary hypertension in newborns, enoximone was also used in piglets to investigate the effects on endotoxin-induced, dopamine-resistant pulmonary hypertension. Enoximone (1 mg/kg i.v.) was given immediately after E. coli endotoxin (1.5 micrograms/kg i.v.) and inhibited the endotoxin-induced, eicosanoid-mediated pulmonary hypertension, whereas during infusion of dopamine (2 mg/kg/h), no drop in systemic blood pressure could be observed. In the clinical study, six infants with post-cardiac surgery low output syndrome despite maximal catecholamine inotropic support were given enoximone (i.v. bolus of 0.2, 0.5, or 1 mg/kg followed by continuous infusion of 7.5-10 micrograms/kg/min). Continuously measured mixed-venous oxygen saturation increased in a dose-related manner. Cardiac output increased significantly by 28%, accompanied by a decrease of arteriovenous oxygen content difference and O2 utilization ratio. The preliminary results show that intravenous enoximone produces acute useful hemodynamic effects in infants, in particular allowing a weaning of vasoactive amines.

摘要

鉴于之前针对成年人的研究,我们认为依诺昔酮可能对治疗具有治疗抵抗性的心血管功能不全的儿童有用。在临床给药之前,我们研究了依诺昔酮在麻醉并通气的、具有小 stroke 容积和高心率特征的仔猪中的心血管特性。依诺昔酮以递增剂量(0.25、0.5 和 1 mg/kg)静脉给药。通过心率、体循环和肺动脉压以及连续电磁流量对动物进行监测。依诺昔酮引起剂量依赖性的流量增加,而心率和体循环动脉压仅略有变化。关于新生儿持续性肺动脉高压,依诺昔酮也被用于仔猪,以研究其对内毒素诱导的、多巴胺抵抗性肺动脉高压的影响。在静脉注射大肠杆菌内毒素(1.5 微克/千克)后立即给予依诺昔酮(1 毫克/千克静脉注射),它抑制了内毒素诱导的、类花生酸介导的肺动脉高压,而在多巴胺(2 毫克/千克/小时)输注期间,未观察到体循环血压下降。在临床研究中,六名尽管接受了最大剂量儿茶酚胺正性肌力支持但仍患有心脏手术后低输出综合征的婴儿接受了依诺昔酮治疗(静脉推注 0.2、0.5 或 1 毫克/千克,随后以 7.5 - 10 微克/千克/分钟的速度持续输注)。连续测量的混合静脉血氧饱和度呈剂量相关方式增加。心输出量显著增加 28%,同时动静脉氧含量差和 O2 利用率降低。初步结果表明,静脉注射依诺昔酮对婴儿产生急性有益的血流动力学效应,特别是有助于撤掉血管活性胺。

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