左西孟旦在新生猪缺氧-再复氧模型中的血液动力学差异效应。

Differential hemodynamic effects of levosimendan in a porcine model of neonatal hypoxia-reoxygenation.

机构信息

Department of Pediatrics, University of Alberta, Edmonton, Alta., Canada.

出版信息

Neonatology. 2012;101(3):192-200. doi: 10.1159/000329825. Epub 2011 Nov 8.

DOI:10.1159/000329825

PMID:22067461

Abstract

BACKGROUND

Neonatal asphyxia can be complicated by myocardial dysfunction with secondary alterations in pulmonary and regional hemodynamics. Levosimendan is a calcium-sensitizing inotrope that may support cardiac output, but little is known regarding its differential hemodynamic effects in asphyxiated neonates.

METHODS

Mixed breed piglets (1-4 days old, weight 1.6-2.3 kg) were acutely instrumented. Normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h, followed by reoxygenation with 100% (1 h) and then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either levosimendan (0.1 or 0.2 μg/kg/min) or D(5)W (placebo) was infused for 2 h in a blinded, block-randomized fashion (n = 7-8/group). The systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics were compared.

RESULTS

At 0.1 and 0.2 μg/kg/min, levosimendan significantly increased cardiac output (121 and 123% of pretreatment, respectively) and heart rate, and decreased systemic vascular resistance without causing hypotension. Pulmonary arterial pressure and estimated pulmonary vascular resistance were significantly increased from pretreatment baseline in 0.1 but not 0.2 μg/kg/min levosimendan. Levosimendan infusion had no effects on regional hemodynamics. Myocardial efficiency but not oxygen consumption increased with 0.1 μg/kg/min levosimendan without significant effects on plasma troponin and myocardial lactate levels.

CONCLUSIONS

In newborn piglets following hypoxia-reoxygenation injury, levosimendan improves cardiac output but has no marked effects in carotid, superior mesenteric and renal perfusion. It appears that various doses of levosimendan increase the cardiac output through different mechanisms. Further investigations are needed to examine the effectiveness of levosimendan as a cardiovascular supportive therapy either alone or in conjunction with other inotropes in asphyxiated neonates.

摘要

背景

新生儿窒息可导致心肌功能障碍，继而引起肺和区域性血液动力学改变。左西孟旦是一种钙离子增敏正性肌力药，可增加心输出量，但对于窒息新生儿的差异血液动力学效应知之甚少。

方法

急性仪器化杂交品种小猪（1-4 天大，体重 1.6-2.3 公斤）。在 2 小时内诱导正常碳酸肺泡缺氧（10-15%氧气），然后用 100%（1 小时）和 21%氧气（3 小时）再氧合。在再氧合 2 小时后，在容量负荷（林格氏乳酸 10 毫升/公斤）后，以盲法、分块随机方式输注左西孟旦（0.1 或 0.2μg/kg/min）或 D（5）W（安慰剂）2 小时（n=7-8/组）。比较全身、肺和区域性（颈动脉、肠系膜上和肾）血液动力学。

结果

左西孟旦 0.1 和 0.2μg/kg/min 时，心输出量（分别为预处理的 121%和 123%）和心率显著增加，全身血管阻力降低而不引起低血压。肺动脉压和估计的肺血管阻力在 0.1μg/kg/min 左西孟旦但不在 0.2μg/kg/min 左西孟旦时从预处理基线显著增加。左西孟旦输注对区域性血液动力学无影响。左西孟旦 0.1μg/kg/min 时心肌效率增加而耗氧量不增加，而对血浆肌钙蛋白和心肌乳酸水平无显著影响。