The effect of oxygen, temperature and hydrogen sulphide on the human pulmonary circulation

Ariyaratnam, Priyadharshanan

Abstract

Introduction: The human pulmonary circulation is poorly understood at a physiological level which is a shame given that the pathology affecting it, particularly pulmonary artery hypertension, can have detrimental effects not only in the lungs but on the heart. Pulmonary artery hypertension in its acute or chronic form carries a high mortality. Few centres have the luxury to utilise human tissue to study this phenomenon. My thesis looks at the effect of certain stimuli such as oxygen, temperature and hydrogen sulphide to discern their role in governing pulmonary artery reactivity at both the tissue and organ level.

Methods: Tissue was supplied from lungs taken from patients with lung cancer following resection of the tumour during surgery. I used a combination of isolated arterial ring models in organ baths and isolated perfused lung models to study the factors governing pulmonary arterial tone and pulmonary artery pressures at a tissue and organ level respectively.

Results: At the tissue level, hypoxia caused nitric-oxide independent dilation of human pulmonary arteries whilst hyperoxia caused a vasoconstriction. This hyperoxic vasoconstriction is dependent on both voltage gated calcium-channels in the cell membrane as well as release from intracellular calcium stores. It is also dependent on oxygen-free radicals. Hypothermia blunts this vasoconstrictive response to hyperoxia as well as endothelin-1 and potassium chloride-mediated pulmonary smooth muscle contraction. Hydrogen sulphide dilates pulmonary arteries. At the organ level, oxygen changes either via the perfusate or the ventilator do not affect pulmonary artery pressures. Both hypothermia and hydrogen sulphide reduce both pulmonary artery pressures and bronchial pressures.

Conclusions: Compensatory mechanisms within the pulmonary circulation may compensate for hypoxic vasodilation and hyperoxic vasoconstriction or there may be a systemic component to entities such as “hypoxic pulmonary vasoconstriction” seen in animal models. Hydrogen sulphide may provide a possible treatment avenue for pulmonary artery hypertension.

Citation

Ariyaratnam, P. The effect of oxygen, temperature and hydrogen sulphide on the human pulmonary circulation. (Thesis). Hull York Medical School, the University of Hull and the University of York. https://hull-repository.worktribe.com/output/4215996

• Thesis Type: Thesis
• Deposit Date: Sep 22, 2014
• Publicly Available Date: Feb 23, 2023
• Keywords: Medicine
• Public URL: https://hull-repository.worktribe.com/output/4215996
• Additional Information: Hull York Medical School, The University of Hull and the University of York
• Award Date: Apr 1, 2014