Clinical trial NCT03317431: the Effect of Dopamine on Mechanical Ventilation Induced Lung Injury
Official title: the Mechanism of the Downregulation of Dopamine Receptor in Mechanical Ventilation Induced Lung Injury
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Lung Injury
Keywords: dopamine,mechanical ventilation,lung injury
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2017-10-23
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients undergo elective lobectom

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Patients inclusion criteria: undergo elective lobectomy with general anesthesia and mechanical ventilation; classified as physical status I to III according to the American Society of Anesthesiologists Physical Status Classification System; Written informed consent is approved.

Exclusion Criteria:

* Distant metastases: recent anaesthetics or mechanical ventilation treatment；children；women during pregnancy or lactation; being involved in other clinical subjects.

Primary outcomes:
measure: Correlation Coefficient (r) Between Duration of Mechanical Ventilation and DRD1 Expression
timeFrame: 20min-60min
Secondary outcomes:
measure: Correlation Coefficient (r) Between Duration of Mechanical Ventilation and DRD2 Expression
timeFrame: 20min-60min
measure: the Expression of TH in Lung Tissues
timeFrame: 20min-60min
measure: the Expression of DDC in Lung Tissues
timeFrame: 20min-60min
measure: the Expression of Ac-a-tubulin in Lung Tissues
timeFrame: 20min-60min
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Anesthesia, Shanghai Xinhua hospital
state: Shanghai
Study officials:
affiliation: Xinhua Hospital affiliated to Medicine school,Shanghai Jiaotong University
name: Lai Jiang, chief doctor
role: STUDY_CHAIR
References: