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Title: Perioperative Lung Injury in Cardiothoracic Surgery: From Bench to Bedside
Author: Ng, Calvin
ISNI:       0000 0001 3444 904X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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The use ofCPB is associated with significant lung dysfunction. Apart from factors such as, hypothermia, systemic heparinisation, and the artificial circuit itself, lung injury can result from pulmonary IR. The lungs have a unique trimodal oxygen supply for lung tissue oxygenation; bronchial arteries, pulmonary arteries, and oxygen from alveolar ventilation. During CPB, only a compromised low pressure bronchial artery perfusion to the lupgs is maintained, therefore a certain degree of lung ischemia is inevitable. Pulmonary ischemia and subsequent reperfusion injury causes a k>cal and systemic inflammatory response, and lung cellular necrosis and apoptosis, resulting in lung dysfunction. The significance of stopping ventilation during clinical CPB in the development of lung IR and inflammation is unknown. Furthermore, apoptosis ofthe lung tissue following IR involves a complex network of interacting enzyme pathways, which over the past decade, are becoming clearer. However, the early and upstream intracellular molecules which promote the expression of these apoptotic enzymes remain to be elucidated. Microarray is a powerful tool which has been used in lung tissue to detect gene expression changes following various insults, including ventilator induced lung injury and ischemia reperfusion. The previous studies of lung IR have focus on microarray gene expression changes following lung transplant in a rodent model, and also pulmonary artery occlusion for 4 to 72 hours in a murine model. Although they are in themselves invaluable to the understanding ofgene expression changes following lung IR, nevertheless those studies do not reflect conditions oflung IR. encountered during the more common procedures ofcoronary artery bypass grafting or valve replacement when lung ischemia times are much shorter. The murine model maintains nonnal ventilation and bronchial artery blood flow to ischemic lung, which is different from lung ischemia encountered during clinical CPB when ventilation is stopped and bronchial blood flow and pressure is reduced. In the first part ofthe study, the effects ofshort durations of lung ischaemia and reperfusion (without ventilation, and with low/no bronchial artery flow), which closely reflect conditions encountered during routine clinical coronary artery bypass graft and valve surgery, on early gene expression changes in the lungs involved in pulmonary apoptosis and inflammation is investigated using an experimental rodent model oflung IR. injury. It is hoped that important insight is gained into the early mechanisms oflung IR following CPB in clinical cardiac surgery. The second part is a clinical randomized prospective study, investigating the effects ofrestoring a source ofoxygenation by maintaining ventilation to the lung during clinical CPB, and how it may affect the degree ofischemia and subsequent reperfusion injury, associated pulmonary and systemic inflammatory and cytokine responses, and cardiovascular-pulmonary function following open heart surgery. The study will improve. our understanding ofthe mechanisms behind, and the relative contribution ofstopping ventilation during CPB towards postoperative pulmonary dysfunction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available