Sevoflurane prevents pulmonary vascular remodeling and right ventricular dysfunction in pulmonary arterial hypertension in rats

Wenqian Zhai; Yunfei Li; Yongjuan Luo; Weidong Gao; Shan Liu; Jiange Han; Jie Geng

Sevoflurane prevents pulmonary vascular remodeling and right ventricular dysfunction in pulmonary arterial hypertension in rats

Am J Transl Res. 2021 Oct 15;13(10):11302-11315. eCollection 2021.

Authors

Wenqian Zhai¹, Yunfei Li¹, Yongjuan Luo², Weidong Gao³, Shan Liu⁴, Jiange Han¹, Jie Geng⁵

Affiliations

¹ Department of Anesthesiology, Tianjin Chest Hospital Tianjin 300222, China.
² Department of Ultrasonics, Tianjin Chest Hospital Tianjin 300222, China.
³ Department of Anesthesiology & Critical Care Medicine, Johns Hopkins University School of Medicine Baltimore 21205, MD, USA.
⁴ Tianjin Cardiovascular Institute, Tianjin Chest Hospital Tianjin 300051, China.
⁵ Department of Cardiology, Tianjin Chest Hospital Tianjin 300222, China.

PMID: 34786059
PMCID: PMC8581939

Abstract

Background: The cardioprotective properties of sevoflurane have been reported in studies of the left ventricle. However, whether this volatile anesthetic would also be beneficial for pulmonary vascular remodeling and associated right ventricular hypertrophy (RVH) remained to be explored. Here, we investigated the potential benefit of sevoflurane to right heart function in experimental pulmonary arterial hypertension (PAH).

Methods: Adult Wistar rats received one dose peritoneal injection of monocrotaline (MCT, 60 mg/kg) or the equal volume of normal saline. Two weeks later, rats were treated with sevoflurane or sham exposure. PAH status and cardiac function were assessed by echocardiography weekly, and the body weight (BW) was monitored every week. After 6 weeks of exercise, Fulton's index calculation, histological observation, IL-6 and TNF-α immunohistochemical analyses, evaluation of MDA, SOD and GSH-Px levels and NF-κB and MAPK active determination were performed in lung and RV tissue samples.

Results: MCT induced pulmonary vascular remodeling, RVH, increased Fulton's index (P<0.01), and right ventricular failure (RVF) in rats. Animals inhaled sevoflurane had an increased cardiac output (P<0.05) and lower incidence of RVF (P<0.05). Also, these animals had a reduced RVEDD, RVWTd and PAID (P<0.05), increased PV (P<0.05), reduced wall thickness and vascular wall area of pulmonary small vascular (vascular external diameter 50-150 um) (P<0.01), reduced RV fibrosis, and increased RV cardiomyocyte area (P<0.01). Furthermore, sevoflurane reduced IL-6 and TNF-α expression in lungs and heart (P<0.01), decreased level of MDA (P<0.01) and increased activity of SOD and GSH-Px (P<0.01). In addition, it decreased the activities of NF-κB and MAPK pathways (P<0.01).

Conclusion: Sevoflurane reduces pulmonary vascular remodeling and RVH in PAH induced by MCT in rats. This effect is likely due to down-regulation of inflammatory factors IL-6 and TNF-α, reduced level of oxidative stress and the inhibition of NF-κB and MAPK pathways.

Keywords: Pulmonary arterial hypertension (PAH); right ventricular failure (RVF); right ventricular hypertrophy (RVH); sevoflurane.