Impacts of inflammatory mediators and hypoxia on vascular reactivity: a model of COPD

Gassama, Abubacarr Kawsu (2018). Impacts of inflammatory mediators and hypoxia on vascular reactivity: a model of COPD. University of Birmingham. Ph.D.

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Abstract

Chronic obstructive pulmonary disease (COPD) is characterized with a poorly reversible airflow limitation. It is a major public health challenge in many developed countries. Cardiovascular complication is a common comorbidity in COPD and is linked to hypoxia and inflammation. Arterial stiffness is also correlated with
emphysema severity in COPD patients, with a suggestion that this might be related to systemic inflammation. In this thesis, we have looked to identify the potential interaction of hypoxia and inflammation upon arterial stiffness of alpha-1 antitrypsin deficient subjects. In addition, we investigated the influence of inflammatory
mediators and hypoxia on vascular dysfunction in an in vivo and in vitro rat model. Our results have shown that serum TN F-a levels correlated positively and significantly with arterial stiffness as measured by pulse wave velocity (PWV). Regression analysis revealed that TNF-a is not an independent predictor of PWV. However, when combined in a regression model with age, sex, Forced Expiratory Volume in 1 second, systolic pressure and gas transfer factor TLCO, The model was effectively able to predict PWV. There was no significant interaction observed between hypoxia and inflammation to modulate arterial stiffness. In a rat model, we found that TNF-a had significant effect upon pulmonary vascular dilatation in response to carbachol and sodium nitroprusside. Hypoxia applied for 1-2 weeks in vivo had no effect upon of vascular reactivity. However, when combined with hypoxia, the effect ofTNF-a on vasodilation was further impaired. These data suggest that a combination of inflammation and hypoxia can have a combined and detrimental effect upon vascular reactivity and so provide a potential model for studying these exacerbations in vitro.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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