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七氟醚对肺动脉高压大鼠模型血流动力学及诱导型一氧化氮合酶/可溶性鸟苷酸环化酶信号通路的影响

Effects of Sevoflurane on Hemodynamics and Inducible Nitric Oxide Synthase/Soluble Guanylate Cyclase Signaling Pathway in a Rat Model of Pulmonary Arterial Hypertension.

作者信息

Qin Gang, Luo Hui, Yin Xiaoqing, Wang Lu, Zhang Junjie, Cao Yanan, Zhang Zhong, Ye Zhi, Wang E

机构信息

From the Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Anesth Analg. 2017 Jul;125(1):184-189. doi: 10.1213/ANE.0000000000001937.

DOI:10.1213/ANE.0000000000001937
PMID:28301419
Abstract

BACKGROUND

The effects of sevoflurane on right ventricular (RV) function are incompletely understood. In a rat model of experimentally induced pulmonary arterial hypertension (PAH), we studied effects of sevoflurane on RV function and the expression of inducible nitric oxide synthase/soluble guanylate cyclase (iNOS/sGC) signaling pathway. We hypothesized that sevoflurane would improve RV function in rats with PAH via a iNOS/sGC pathway.

METHODS

To induce PAH, Sprague-Dawley rats were randomly assigned to treatment with monocrotaline or normal saline. Four weeks later, rats were then randomly assigned to either control or sevoflurane inhalation. After rats were anesthetized and instrumented with a pulmonary artery or RV conductance catheter, they were treated with inhaled sevoflurane at 3 doses for 90 minutes each. Hemodynamic changes and expression of iNOS and sGC were recorded.

RESULTS

Sevoflurane inhalation depressed RV function in both normal and PAH rats. However, RV dP/dtmax fell to a lesser degree in rats with PAH than normal rats. Sevoflurane inhalation increased iNOS expression, but decreased sGC expression.

CONCLUSIONS

Sevoflurane depressed RV contractility to a lesser degree in PAH than in normal rats. Sevoflurane also upregulated iNOS expression and downregulated sGC expression in PAH, but not control rats. This observation may explain the differential effects of sevoflurane on RV function in rats with and without PAH.

摘要

背景

七氟醚对右心室(RV)功能的影响尚未完全明确。在实验性诱导肺动脉高压(PAH)的大鼠模型中,我们研究了七氟醚对RV功能以及诱导型一氧化氮合酶/可溶性鸟苷酸环化酶(iNOS/sGC)信号通路表达的影响。我们假设七氟醚可通过iNOS/sGC途径改善PAH大鼠的RV功能。

方法

为诱导PAH,将Sprague-Dawley大鼠随机分为用野百合碱或生理盐水治疗组。四周后,再将大鼠随机分为对照组或七氟醚吸入组。大鼠麻醉后植入肺动脉或RV电导导管,然后分别用3种剂量的吸入七氟醚治疗,每种剂量治疗90分钟。记录血流动力学变化以及iNOS和sGC的表达。

结果

吸入七氟醚使正常大鼠和PAH大鼠的RV功能均降低。然而,PAH大鼠的RV dP/dtmax下降程度小于正常大鼠。吸入七氟醚增加了iNOS表达,但降低了sGC表达。

结论

与正常大鼠相比,七氟醚对PAH大鼠RV收缩力的抑制程度较小。七氟醚还上调了PAH大鼠而非对照组大鼠的iNOS表达并下调了sGC表达。这一观察结果可能解释了七氟醚对有或无PAH大鼠RV功能的不同影响。

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