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硝普钠在兔实验性大块肺栓塞伴循环休克模型中的即刻有益作用。

Acute Beneficial Effects of Sodium Nitroprusside in a Rabbit Model of Massive Pulmonary Embolism Associated with Circulatory Shock.

机构信息

Department of Cardiology, Wuhan Puai Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Department of Pathology, Wuhan Puai Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

出版信息

Am J Pathol. 2018 Aug;188(8):1768-1778. doi: 10.1016/j.ajpath.2018.04.014. Epub 2018 May 25.

DOI:10.1016/j.ajpath.2018.04.014
PMID:29803832
Abstract

We established a rabbit model of acute massive pulmonary embolism (PE) with associated circulatory shock using autologous blood clots. Rabbits were randomly assigned to a sham operation group (S group), model group (M group; equal volume of saline intravenously after shock), and sodium nitroprusside group (SNP group; sodium nitroprusside intravenously after shock). SNP treatment significantly decreased mean pulmonary arterial pressure and increased mean arterial pressure and arterial partial pressure of oxygen and resulted in a partial reversal of the acute circulatory failure. The shock-reversal rate was 0% in the M group and 80% in the SNP group. Moreover, pulmonary artery angiography and echocardiography examinations evidenced alleviated PE-induced changes after SNP therapy. 5-Hydroxytryptamine was significantly reduced in both PE and non-PE tissues, thromboxane A level was significantly reduced in PE and tended to be lower in non-PE tissues, neutrophil accumulation was significantly reduced in both PE and non-PE tissues after SNP therapy. Our study demonstrated that pulmonary vasospasm in the nonembolic region might be a major pathologic factor leading to reduced left ventricular filling and circulatory shock after massive PE. Reduction of pulmonary vasospasm in the nonembolic area after SNP might serve as a major therapeutic mechanism involved in the observed beneficial effects of SNP in this model.

摘要

我们使用自体血凝块建立了伴有循环休克的急性大面积肺栓塞(PE)兔模型。兔子被随机分配到假手术组(S 组)、模型组(M 组;休克后静脉注射等量生理盐水)和硝普钠组(SNP 组;休克后静脉注射硝普钠)。SNP 治疗显著降低平均肺动脉压,增加平均动脉压和动脉血氧分压,并部分逆转急性循环衰竭。M 组休克逆转率为 0%,SNP 组为 80%。此外,肺动脉造影和超声心动图检查显示 SNP 治疗后 PE 诱导的变化得到缓解。5-羟色胺在 PE 和非 PE 组织中均显著减少,血栓素 A 水平在 PE 组织中显著减少,在非 PE 组织中趋于降低,SNP 治疗后 PE 和非 PE 组织中的中性粒细胞聚集均显著减少。我们的研究表明,非栓塞区域的肺血管痉挛可能是导致大量 PE 后左心室充盈减少和循环休克的主要病理因素。SNP 降低非栓塞区的肺血管痉挛可能是 SNP 在该模型中观察到的有益作用的主要治疗机制之一。

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Sodium nitroprusside improves circulatory failure in rabbit acute pulmonary embolism combined with shock model possibly by enhancing NO release and inhibiting TLR4/NF-кB/HIF-1α signaling pathway.硝普钠可能通过增强一氧化氮释放和抑制Toll样受体4/核因子-кB/缺氧诱导因子-1α信号通路,改善兔急性肺栓塞合并休克模型中的循环衰竭。
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