Oxygenation in human pulmonary microvasculature and small airways

• Research type

  Research Study

• Full title

  The impact of oxygen on human pulmonary microvasculature and small airways

• IRAS ID

  190181

• Contact name

  Azar Hussain

• Contact email

  azar.hussain@hey.nhs.uk

• Sponsor organisation

  Research & Development Department

• Duration of Study in the UK

  1 years, 6 months, 3 days

• Research summary

  Pulmonary hypertension (PH) is a haemodynamic and pathophysiological condition defined as an increase in mean pulmonary arterial pressure (PAP) &¡Ý25 mmHg at rest as assessed by right heart catheterization. Pulmonary circulation in general and pulmonary hypertension in particular is a neglected area and little research has been performed to understand the pathophysiology of pulmonary hypertension.
  Research work carried out in our department looked into the effect of oxygen on larger pulmonary vessels and showed that at tissue level, hypoxia caused nitric-oxide independent dilation of human pulmonary arteries whilst hyperoxia caused a vasoconstriction, whereas at the organ level, oxygen changes did not affect pulmonary artery pressures.

  Objectives:
  1- To establish the role of oxygen on pulmonary microvasculature and small airways.
  2- To assess whether small and large pulmonary vessels respond in a similar manner.
  3- Aim to identify possible therapeutic strategies to ameliorate pulmonary hypertension.

  STUDY DESIGN / METHODOLOGY:
  The sample will be collected from theatre and placed into physiological saline and taken directly to research laboratory. Pulmonary arteries and small airways will be dissected from disease free area of lung resection and cut into rings of appropriate diameter. Multiwire myograph unit will be used for these experiments. Smaller vessels will be connected to stainless steel mounting jaws and mounting pins will be used for larger vessels. One of the myograph jaws need to be connected to micro positioner and the other jaw will be connected to force transducer.
  Sample will be immersed into physiological saline solution and aerated with 21%O2 / 5%CO2 and maintained at pH 7.4. Temperature, pH and weight of the sample will be continually recorded. Following equilibration tissue sample will be exposed to 70mM Potassium chloride to confirm vascular viability. Sample will than be washed with Krebs bicarbonate solution and allowed to re-equilibrate. After stability sample will be exposed to a hypoxic gas mixture consisting of 95% N2 / 5%CO2 for 30 minutes. Following this the sample will be re-oxygenated with 95%O2 / 5%CO2 for 45 minutes and reading will be recorded.
  Another study group will follow the exact protocol as above but will be exposed to various conditions such as endothelial smooth muscle antagonists and dilators, gastrotrnasmitters such as hydrogen sulphide, as well as bronchial antagonists and dilators. These conditions may enhance or inhibit the hypoxia-reoxygenation effects

  EXPECTED OUTCOMES OF STUDY:
  These studies aim to have a better understanding of the response of pulmonary vessels and bronchial airways to oxygen and use this knowledge in clinical practice to reduce the chances of development of post-surgical pulmonary hypertension. This may have an impact in intra-operative management of patients undergoing cardiac and thoracic surgery

• REC name

  North West - Liverpool Central Research Ethics Committee

• REC reference

  15/NW/0808

• Date of REC Opinion

  30 Sep 2015

• REC opinion

  Favourable Opinion