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未分级肝素改善犬脓毒性休克模型的肠道微循环。

Unfractionated Heparin Improves the Intestinal Microcirculation in a Canine Septic Shock Model.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang, China.

Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

出版信息

Mediators Inflamm. 2021 Jun 23;2021:9985397. doi: 10.1155/2021/9985397. eCollection 2021.

DOI:10.1155/2021/9985397
PMID:34257522
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8245220/
Abstract

BACKGROUND

Alterations of microcirculation are associated with organ hypoperfusion and high mortality in septic shock. This study is aimed at investigating the effects of unfractionated heparin (UFH) on intestinal microcirculatory perfusion and systemic circulation in a septic shock model.

METHODS

Twenty-four beagle dogs were randomly allocated into four groups: (a) sham group: healthy controls, (b) shock group: septic shock induced by , (c) basic therapy group: septic shock animals treated with antibiotics and 10 ml/kg/h saline, and (d) heparin group: septic shock animals treated with basic therapy plus UFH. Hemodynamic variables were measured within 24 h after administration. The intestinal microcirculation was simultaneously investigated with a sidestream dark-field imaging technique. Additionally, the function of vital organs was evaluated at 12 h postadministration (T12).

RESULTS

induced a progressive septic shock in which the mean arterial pressure (MAP) decreased and lactate levels sharply increased, accompanied by deteriorated microvessel perfusion. While basic therapy partially improved the microvascular flow index and the perfused microvessel density in the jejunal villi, UFH significantly restored major microcirculation variables at T12. Physiological variables, including MAP, urine output, and lactate levels, were improved by UFH, whereas some hemodynamic indices were not affected by UFH. With respect to organ function, UFH increased the platelet count and decreased the creatinine level.

CONCLUSIONS

UFH improves microcirculatory perfusion of the small intestine independently of the changes in systemic hemodynamic variables in a canine model of septic shock, thereby improving coagulation and renal function.

摘要

背景

微循环的改变与感染性休克中的器官灌注不足和高死亡率有关。本研究旨在研究未分级肝素(UFH)对感染性休克模型中肠道微循环灌注和全身循环的影响。

方法

将 24 只比格犬随机分为四组:(a)假手术组:健康对照;(b)休克组:通过 诱导的感染性休克;(c)基础治疗组:用抗生素和 10ml/kg/h 生理盐水治疗的感染性休克动物;(d)肝素组:用基础治疗加 UFH 治疗的感染性休克动物。在 给药后 24 小时内测量血流动力学变量。同时用侧流暗场成像技术对肠道微循环进行研究。此外,在给药后 12 小时(T12)评估重要器官的功能。

结果

诱导出进行性感染性休克,平均动脉压(MAP)降低,乳酸水平急剧升高,伴有微血管灌注恶化。虽然基础治疗部分改善了空肠绒毛的微血管血流指数和灌注的微血管密度,但 UFH 在 T12 时显著恢复了主要的微循环变量。生理变量,包括 MAP、尿量和乳酸水平,都得到了 UFH 的改善,而一些血流动力学指数不受 UFH 的影响。就器官功能而言,UFH 增加了血小板计数,降低了肌酐水平。

结论

UFH 改善了感染性休克犬模型中小肠的微循环灌注,而不改变全身血流动力学变量,从而改善凝血功能和肾功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/9a371f71b679/MI2021-9985397.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/869b2148b4dd/MI2021-9985397.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/0b4e656a01e5/MI2021-9985397.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/8725329a30ac/MI2021-9985397.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/a23343a33a00/MI2021-9985397.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/9af4a8b34411/MI2021-9985397.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/9a371f71b679/MI2021-9985397.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/869b2148b4dd/MI2021-9985397.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/393df7e3edb2/MI2021-9985397.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/0b4e656a01e5/MI2021-9985397.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/8725329a30ac/MI2021-9985397.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/a23343a33a00/MI2021-9985397.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/9af4a8b34411/MI2021-9985397.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd64/8245220/9a371f71b679/MI2021-9985397.007.jpg

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J Trauma Acute Care Surg. 2019 Sep;87(3):614-622. doi: 10.1097/TA.0000000000002387.
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Challenges in the management of septic shock: a narrative review.
脓毒性休克管理面临的挑战:叙事性综述。
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Unfractionated heparin ameliorates pulmonary microvascular endothelial barrier dysfunction via microtubule stabilization in acute lung injury.未分级肝素通过稳定微管改善急性肺损伤肺微血管内皮屏障功能障碍。
Respir Res. 2018 Nov 15;19(1):220. doi: 10.1186/s12931-018-0925-6.
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The role of heparin in sepsis: much more than just an anticoagulant.肝素在脓毒症中的作用:远不止是一种抗凝剂。
Br J Haematol. 2017 Nov;179(3):389-398. doi: 10.1111/bjh.14885. Epub 2017 Aug 18.
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The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).《脓毒症及脓毒性休克第三次国际共识定义(脓毒症-3)》
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