NCT03317431

the Effect of Dopamine on Mechanical Ventilation Induced Lung Injury

the Mechanism of the Downregulation of Dopamine Receptor in Mechanical Ventilation Induced Lung Injury

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 46 (actual)
• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

Dopamine(DA) is a common neurotransmitter that has been known to regulate behavior, movement, cardiovascular，endocrine and gastrointestinal functions, but also functions as an important molecule engaging in the immune systems to possess anti-inflammatory effects. However, its role in ventilator-induced lung injury (VILI) is still unclear. Herein, this study aimed to investigate the therapeutic efficacy of dopamine on ventilation-induced lung endothelial barrier dysfunction and explore the possible underlying molecular mechanisms.

Detailed description

Mechanical ventilation is a critical intervention for patients with acute respiratory failure. However, lung overdistension induced by mechanical ventilation at high tidal volumes also causes pulmonary endothelial dysfunction. The injurious effect of mechanical stretch on pulmonary endothelium has been implicated in the development of ventilator-induced lung injury (VILI), which is characterized by pulmonary inflammation and particularly increased vascular permeability. In addition, the investigators and others have previously shown that mechanical stretch increases cultured lung endothelial monolayer permeability in vitro and promotes lung vascular permeability in mice Thus, elucidating the mechanisms underlying the mechanical stretch-induced lung endothelial barrier dysfunction may provide a novel clinical therapeutic target against VILI. Dopamine is a neurotransmitter, which can also be produced outside the central nervous system. Lung alveolar epithelial cells represent an important source of extraneuronal dopamine, which has a significant role in local organ physiology. Dopamine D1 receptor (DRD1) and D2 receptor (DRD2) are present in lung tissues. Activation of D2DR induces NaKATPase gene expression. Moreover, activation of DRD1 results in the trafficking of NaKATPase to the basolateral membrane of type II alveolar epithelial cells, thus increasing lung liquid clearance during acute lung injury. Although the lung-protective effects of DA and its implication in the pathology of ALI are emerging, the mechanisms are still largely unknown. In the present study, the investigators will analyze the influence of mechanical ventilation on dopamine receptors in the lung tissue of the participants, and explore whether DA could protect ventilation induced lung injury, which is helpful for prevention and treatment of ventilation induced lung injury.

Conditions

• Acute Lung Injury

Interventions

Type	Name	Description
OTHER	mechanical ventilation	mechanical ventilation protocol: tidal volume 6-8 ml/kg, positive end-expiratory pressure 5 cmH2O, oxygen concentration 40%; respiratory rate 10-15/min, inspiratory/expiratory ratio 1:1.5.

Timeline

• Start date: 2017-03-20
• Primary completion: 2017-10-22
• Completion: 2017-12-01
• First posted: 2017-10-23
• Last updated: 2018-10-22
• Results posted: 2018-10-22

Locations

1 site across 1 country: China