ARS Project/Heath Family Grant
The successful applicant for the ARS Project/Heath Family Grant was:
Principal Applicant
Dr T Smith
Academic Clinical Fellow, Nuffield Department of Anaesthetics, University of Oxford, John Radcliffe Hospital, Oxford
Title
Ascorbate (vitamin C) and hypoxic pulmonary hypertension
Amount
£9,680
Abstract
My research has established that iron profoundly affects the pulmonary hypertensive response to hypoxia caused by hypoxic pulmonary vasoconstriction, which is an important physiological response in anaesthesia (e.g. one-lung ventilation) and in intensive care medicine (e.g. acute respiratory distress syndrome). In particular, intravenous iron can prevent and reverse hypoxic pulmonary hypertension, apparently through effects on a transcription factor called hypoxia-inducible factor (HIF). HIF controls responses to hypoxia both intracellularly and at the systemic cardiopulmonary level, and is sensitive to both iron and ascorbate (vitamin C) availability. Ascorbate may therefore affect the lungs in the same way that iron does, and would be a safer therapeutic alternative to iron. This study aims to determine whether intravenous ascorbate (dose 2 g) inhibits the increase in pulmonary arterial pressure caused by subsequent hypoxia. 12 healthy volunteers will be exposed to 8 hours of hypoxia in our laboratory's purpose-built hypoxia chamber (end-tidal partial pressure of oxygen 50 mmHg [). The study will be randomized, double-blind, placebo-controlled and crossover in design, with each volunteer acting as their own control. The primary outcome measure will be pulmonary artery systolic pressure measured by Doppler echocardiography.
Interim report from Dr T Smith (67 KB)
Final report published in Wiley Online's Physiological Report .
