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低剂量血管加压素改善急性低氧复氧新生仔猪心功能。

Low-dose vasopressin improves cardiac function in newborn piglets with acute hypoxia-reoxygenation.

机构信息

*Departments of Surgery, †Laboratory Medicine and Pathology, ‡Cell Biology, and §Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

出版信息

Shock. 2013 Oct;40(4):320-6. doi: 10.1097/SHK.0b013e3182a4284e.

Abstract

Cardiovascular dysfunction in asphyxiated neonates contributes significantly to their morbidity and mortality. We have recently shown that a low-dose vasopressin infusion (0.005 - 0.01 units/kg per hour) may improve myocardial oxygen transport balance in a swine model of neonatal hypoxia-reoxygenation. We aimed to compare the systemic and regional hemodynamic effects of low-dose vasopressin to dobutamine, a synthetic beta-adrenoreceptor agonist. Piglets (1 - 5 days old, 1.6 - 2.2 kg) were anesthetized and instrumented to continuously monitor systemic hemodynamic parameters, including cardiac output and mesenteric flow indices. After 2 h of hypoxia (10% - 15% O2), piglets had normoxic reoxygenation for 4 h. In a blinded randomized fashion, piglets received infusion of either vasopressin (0.01 units/kg per hour started at 30 min of reoxygenation) or dobutamine (20 μg/kg per minute started at 2 h of reoxygenation) (n = 8 per group). Hypoxia-reoxygenation controls (placebo, n = 8) and sham-operated (n = 5) piglets were also studied. Tissue lactate, glutathione, glutathione disulfide, and lipid hydroperoxides levels and histology of the left ventricle and the small bowel were analyzed. Plasma was also analyzed for troponin-I and intestinal fatty acid-binding protein levels. Piglets subjected to hypoxia-reoxygenation had cardiogenic shock and metabolic acidosis, which improved on reoxygenation. During recovery, cardiac output and mesenteric flows gradually deteriorated and were increased similarly in vasopressin- and dobutamine-treated piglets (P < 0.05 vs. controls). Plasma troponin-I and left ventricular lactate levels were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls), with no difference in the histological analysis among groups. The intestinal GSSG/GSH ratio and lipid hydroperoxides level were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls). This study is the first to demonstrate that a low-dose vasopressin infusion used in the setting of neonatal swine model of hypoxia-reoxygenation is associated with an improvement in cardiac output and mesenteric perfusion.

摘要

窒息新生儿的心血管功能障碍对其发病率和死亡率有重要影响。我们最近的研究表明,小剂量血管加压素输注(0.005-0.01 单位/千克/小时)可能改善新生猪缺氧-再氧合模型中的心肌氧运输平衡。我们旨在比较小剂量血管加压素和多巴酚丁胺(一种合成的β-肾上腺素能受体激动剂)对全身和局部血流动力学的影响。小猪(1-5 天大,1.6-2.2 公斤)麻醉并植入仪器以连续监测全身血流动力学参数,包括心输出量和肠系膜流量指数。在缺氧 2 小时(10%-15%O2)后,小猪进行 4 小时的正常氧再灌注。在盲法随机的方式下,小猪接受血管加压素输注(0.01 单位/千克/小时,在再氧合 30 分钟开始)或多巴酚丁胺输注(20μg/kg/分钟,在再氧合 2 小时开始)(每组 8 只)。缺氧-再氧合对照组(安慰剂,n=8)和假手术组(n=5)也进行了研究。分析了左心室和小肠的组织乳酸、谷胱甘肽、二硫谷胱甘肽、脂质氢过氧化物水平和组织学,并分析了血浆肌钙蛋白 I 和肠脂肪酸结合蛋白水平。接受缺氧-再氧合的小猪发生心源性休克和代谢性酸中毒,在再氧合时得到改善。在恢复期间,心输出量和肠系膜流量逐渐恶化,血管加压素和多巴酚丁胺治疗的小猪心输出量和肠系膜流量增加相似(与对照组相比,P<0.05)。血管加压素和多巴酚丁胺组的血浆肌钙蛋白 I 和左心室乳酸水平较低(与对照组相比,P<0.05),但各组的组织学分析无差异。血管加压素和多巴酚丁胺组的肠 GSSG/GSH 比值和脂质氢过氧化物水平较低(与对照组相比,P<0.05)。本研究首次证明,在新生猪缺氧-再氧合模型中使用小剂量血管加压素输注可改善心输出量和肠系膜灌注。

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