Inhibition of RHO Kinase by Fasudil Attenuates Ischemic Lung Injury After Cardiac Arrest in Rats. Issue 6 (December 2018)

• Record Type: Journal Article
• Authors: Wei, Jian; Wang, Peng; Li, Yi; Dou, Qingli; Lin, Jiali; Tao, Wuyuan; Lin, Jinle; Fu, Xuan; Huang, Zitong; Zhang, Wenwu
• Is Part Of: Shock. Volume 50:Issue 6(2018)
• Publication Date: 2018-12
• Subjects: Cardiac arrest -- Fasudil -- lung injury -- Rho/ROCK; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000001097
• Languages: English
• ISSNs: 1073-2322

Abstract

Abstract : ABSTRACT: Lung injury is a common complication after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), and Rho kinase (ROCK) may be involved in the process of this injury. In this study, we aimed to study the effects of ROCK inhibition by fasudil on lung injury induced by asphyxial CA and CPR in rats. A total of 130 rats were randomized into three groups: Sham, Control, and Fasudil intervention group. Animals in the Fasudil intervention group were intraperitoneally administered with 10 mg/kg of the drug, 1 h before inducing CA. Rats in the Control group received equivalent volume of saline and were subjected to the same experimental procedures with as the Fasudil group. Blood was collected and lungs were harvested at 3, 6, 12, 24, and 48 h after return of spontaneous circulation (ROSC) for blood gas and biochemical analysis. Fasudil significantly increased the partial pressure of oxygen and pH in arterial blood, as well as attenuated lung histological injury and lung edema after ROSC. Additionally, it significantly decreased lung inflammatory response (decreased levels of tumor necrosis factor-α and interleukin-6, and myeloperoxidase activity) and oxidative stress (decreased malonaldehyde level and increased superoxide dismutase activity) after ROSC. Using western blot analysis, we found that fasudil inhibited both isoforms ROCK1 and ROCK2, and intercellular adhesion molecule-1; nevertheless, it increased vascular endothelial cadherin protein expression after ROSC. Our study suggested that the Rho kinase signaling pathway is critical for CA-induced lung injury and fasudil has protective effects on lung injury after CA and CPR. Abstract : Supplemental Digital Content is available in the text