the Effect of Dopamine on Mechanical Ventilation Induced Lung Injury
Condition: Acute Lung Injury
MeSH terms: Lung Injury; Acute Lung Injury; Wounds and Injuries
Study type: Observational

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.
    

Intervention name(s): mechanical ventilation
Intervention type(s): Other
Intervention description(s): 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.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        patients undergo elective lobectom
      
Biospecimen description: 
      Gather the lung tissues from patients undergo lobectomy with general anesthesia and
      mechanical ventilation
    
Keywords: dopamine,mechanical ventilation,lung injury