Breathing In Chronic Heart Failure: Is There Novel Pulmonary Compensation?
Funder
National Health and Medical Research Council
Funding Amount
$312,021.00
Summary
Chronic heart failure (CHF) is a growing modern epidemic and therefore a costly health burden in Australia. Not only is it associated with a high mortality rate, symptoms of CHF are a major cause of patient suffering. Shortness of breath and exercise intolerance are both indicators of a link between CHF and lung function. There are a number of different ways in which CHF may be impacting on breathing and in this project we will be utilising an animal model to examine some of them. Firstly, the l ....Chronic heart failure (CHF) is a growing modern epidemic and therefore a costly health burden in Australia. Not only is it associated with a high mortality rate, symptoms of CHF are a major cause of patient suffering. Shortness of breath and exercise intolerance are both indicators of a link between CHF and lung function. There are a number of different ways in which CHF may be impacting on breathing and in this project we will be utilising an animal model to examine some of them. Firstly, the lung secretes a substance called surfactant which assists in normal breathing by decreasing surface tension in the lung. Previous studies in our laboratory have suggested an increase in surfactant production during CHF. In this project we will further examine this process to see if increased surfactant can aid breathing by decreasing surface tension during CHF. Secondly, we will examine the contribution made by the chest wall, increased heart size, lung volume and blood pressure during CHF on breathing. Thirdly, one of the problems thought to inhibit breathing in CHF patients is an increase in fluid in the lungs. The final stage of this project will examine the trasport of fluid into and out of the lung during CHF. This project will not only increase our understanding of the processes affecting breathing in response to CHF, but will also provide information for the development of potential therapeutic targets.Read moreRead less
Regulation Of The Epithelial Sodium Channel By Cytosolic Chloride And Pro-inflammatory Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$219,750.00
Summary
The regulation of sodium transport by the epithelial sodium channel is essential for the maintenance of blood pressure and the correct amount of fluid in the respiratory tract and gut. Hyperactivity of the sodium channels leads to increased blood pressure and clogging of the gut and bronchi due to dehydration of the surface fluid. Reductions in the activity of the sodium channels lead to abnormally low blood pressure and the accumulation of fluid in the lungs such as occurs in influenza, high al ....The regulation of sodium transport by the epithelial sodium channel is essential for the maintenance of blood pressure and the correct amount of fluid in the respiratory tract and gut. Hyperactivity of the sodium channels leads to increased blood pressure and clogging of the gut and bronchi due to dehydration of the surface fluid. Reductions in the activity of the sodium channels lead to abnormally low blood pressure and the accumulation of fluid in the lungs such as occurs in influenza, high altitude pulmonary oedema and in cardiogenic pulmonary oedema. The present project will examine the mechanisms by which sodium channels are regulated. It will focus on the mechanisms by which cytosolic chloride and inflammatory mediators regulate the activity of the channels.Read moreRead less
Assessment Of Physical Therapies To Improve Secretion Clearance In Patients With Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$302,310.00
Summary
People with cystic fibrosis (CF) produce thick mucus that is not cleared normally from the lungs. This retained mucus often becomes infected, which progressively damages the lungs. Various physical therapies which may help clear secretions are being used in CF. These include several types of devices which provide positive pressure to the airways. However, it is not known to what extent these devices, or other interventions such as manual chest physiotherapy and exercise, enhance mucus clearance. ....People with cystic fibrosis (CF) produce thick mucus that is not cleared normally from the lungs. This retained mucus often becomes infected, which progressively damages the lungs. Various physical therapies which may help clear secretions are being used in CF. These include several types of devices which provide positive pressure to the airways. However, it is not known to what extent these devices, or other interventions such as manual chest physiotherapy and exercise, enhance mucus clearance. As a result, it is not currently possible to scientifically prescribe intervention(s) to enhance mucus clearance in CF. This is partly because much of the research that has been performed in this area has been poorly-designed or has used inaccurate measures. Also, recent research has shown that these therapies may have significant effects beside their effect on mucus clearance. For instance, bacterial infection and the exchange of oxygen and carbon dioxide between the blood supply and air in the lung may all be affected by these interventions. Notably, the extent of benefit or detriment seen in these parameters does not always correlate with the effect on mucus clearance. We therefore believe a series of experiments is necessary to provide evidence upon which the scientific selection of mucus clearance therapies may be based. We have developed a new technique which allows clearance of mucus from the airways to be objectively measured in three-dimensions (3D). We intend to use the 3D technique to examine the effects of three different positive pressure devices, exercise, and manual chest physiotherapy on mucus clearance. Based on the outcomes of this research, we intend to compare the most appropriate therapy to performing no mucus clearance therapy in a short term trial. This trial will assess changes in the following: bacterial infection, mucus plugging in the airways, how well the lungs move air and exchange oxygen and carbon dioxide, and the patient's quality of life.Read moreRead less
Invasive Cardiopulmonary Exercise Testing For The Evaluation Of Unexplained And Complex Multifactorial BREATHlessnEss (i-BREATHE)
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Breathlessness is a common symptom that can be caused by diseases of the heart, lungs or muscles. It is not uncommon that the cause is undiagnosed either because conventional tests do not yield a diagnosis, or because an individual suffers from multiple diseases. This research aims to use invasive cardiopulmonary exercise testing, a highly specialised test which simultaneously measures breathing, heart and muscle function, to improve the diagnosis and treatment of patients with breathlessness.
Novel Cellular Trafficking Mechanisms For The Drug Influx Transporter, Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in indivi ....Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in individuals.Read moreRead less