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亚治疗剂量的血管加压素而非治疗剂量的血管加压素可改善脓毒症大鼠的胃肠微循环:一项随机、安慰剂对照、盲法试验。

Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial.

机构信息

Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, North Rhine-Westphalia, Germany.

出版信息

PLoS One. 2021 Sep 23;16(9):e0257034. doi: 10.1371/journal.pone.0257034. eCollection 2021.

DOI:10.1371/journal.pone.0257034
PMID:34555053
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8460032/
Abstract

INTRODUCTION

Sepsis impairs gastrointestinal microcirculation and it is hypothesized that this might increase patient's mortality. Sub-therapeutic vasopressin improves gastric microcirculation under physiologic conditions whereas a therapeutic dosing regimen seems to be rather detrimental. However, the effects of sub-therapeutic vasopressin on gastrointestinal microcirculation in sepsis are largely unknown. Therefore, we conducted this trial to investigate the effect of sub-therapeutic as well as therapeutic vasopressin on gastrointestinal microcirculation in sepsis.

METHODS

40 male Wistar rats were randomized into 4 groups. Colon ascendens stent peritonitis (CASP)-surgery was performed to establish mild or moderate sepsis. 24 hours after surgery, animals received either vasopressin with increasing dosages every 30 min (6.75, 13.5 (sub-therapeutic), 27 mU · kg-1 · h-1 (therapeutic)) or vehicle. Microcirculatory oxygenation (μHBO2) of the colon was recorded for 90 min using tissue reflectance spectrophotometry. Intestinal microcirculatory perfusion (total vessel density (TVD; mm/mm2) and perfused vessel density (PVD; mm/mm2)) were measured using incident dark field-Imaging at baseline and after 60 min.

RESULTS

In mild as well as in moderate septic animals with vehicle-infusion intestinal μHbO2, TVD and PVD remained constant. In contrast, in moderate sepsis, sub-therapeutic vasopressin with 13.5 mU · kg-1 · h-1 elevated intestinal μHBO2 (+ 6.1 ± 5.3%; p < 0.05 vs. baseline) and TVD (+ 5.2 ± 3.0 mm/mm2; p < 0.05 vs. baseline). μHBO2, TVD and PVD were significantly increased compared to moderate sepsis alone. However, therapeutic vasopressin did not change intestinal microcirculation. In mild septic animals sub-therapeutic as well as therapeutic vasopressin had no relevant effect on gastrointestinal microcirculation. Systemic blood pressure remained constant in all groups.

CONCLUSION

Sub-therapeutic vasopressin improves gastrointestinal microcirculatory oxygenation in moderate sepsis without altering systemic blood pressure. This protective effect seems to be mediated by an enhanced microcirculatory perfusion and thereby increased oxygen supply. In contrast, therapeutic vasopressin did not show this beneficial effect.

摘要

简介

脓毒症会损害胃肠道微循环,据推测这可能会增加患者的死亡率。在生理条件下,低剂量的血管加压素可以改善胃微循环,而治疗剂量的血管加压素似乎反而有害。然而,低剂量血管加压素对脓毒症胃肠道微循环的影响在很大程度上尚不清楚。因此,我们进行了这项试验,以研究低剂量和治疗剂量的血管加压素对脓毒症胃肠道微循环的影响。

方法

将 40 只雄性 Wistar 大鼠随机分为 4 组。通过结肠升支支架腹膜炎(CASP)手术建立轻度或中度脓毒症。手术后 24 小时,动物接受递增剂量的血管加压素(每 30 分钟 6.75、13.5(低剂量)、27 mU·kg-1·h-1(治疗剂量))或载体。使用组织反射光谱光度法记录 90 分钟的结肠微循环氧合(μHBO2)。在基线和 60 分钟后,使用入射暗场成像测量肠道微循环灌注(总血管密度(TVD;mm/mm2)和灌注血管密度(PVD;mm/mm2))。

结果

在轻度和中度脓毒症动物中,接受载体输注的肠道μHbO2、TVD 和 PVD 保持不变。相反,在中度脓毒症中,用 13.5 mU·kg-1·h-1 的低剂量血管加压素可升高肠道μHBO2(+6.1±5.3%;p<0.05 与基线相比)和 TVD(+5.2±3.0 mm/mm2;p<0.05 与基线相比)。与中度脓毒症相比,μHBO2、TVD 和 PVD 均显著增加。然而,治疗剂量的血管加压素并未改变肠道微循环。在轻度脓毒症动物中,低剂量和治疗剂量的血管加压素对胃肠道微循环均无明显影响。所有组的全身血压均保持不变。

结论

低剂量血管加压素可改善中度脓毒症患者的胃肠道微循环氧合,而不改变全身血压。这种保护作用似乎是通过增加微循环灌注和增加氧供应来介导的。相比之下,治疗剂量的血管加压素没有显示出这种有益的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a6/8460032/a214668b124b/pone.0257034.g006.jpg
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