The Role Of The Calcineurin Negative Regulator, DSCR1, In Heart Development And Hypertrophy.
Funder
National Health and Medical Research Council
Funding Amount
$431,310.00
Summary
Congenital heart defects in the young and heart disease later in life place a heavy burden on our society in terms of illness, disability and death and are very costly in terms of the health care budget. Failure of heart valve development and holes in the heart, are very common abnormalities occurring in nearly 1 % of all live births. This type of anomaly is also observed in about 44 % of individuals with Down syndrome, which results when individuals carry an extra copy of chromosome 21. Thus, i ....Congenital heart defects in the young and heart disease later in life place a heavy burden on our society in terms of illness, disability and death and are very costly in terms of the health care budget. Failure of heart valve development and holes in the heart, are very common abnormalities occurring in nearly 1 % of all live births. This type of anomaly is also observed in about 44 % of individuals with Down syndrome, which results when individuals carry an extra copy of chromosome 21. Thus, it is likely that a gene located on human chromosome 21 contributes to this pathology and indeed our work on the identification of genes with the potential to cause the heart defect observed in Down syndrome, has led to the discovery of a gene called DSCR1. DSCR1 is a negative regulator of a biological pathway which when disturbed in the heart can lead to developmental heart malformations, similar to the type seen in Down syndrome, and when over stimulated can result in the abnormal growth of the heart seen in humans with hypertension and heart disease. If we are to make rational decisions about the design of potential treatments for heart defects and disease, we firstly need to understand how these biological pathways work and how molecules such as DSCR1 regulate them. We aim to investigate how DSCR1 functions by generating mice that lack the gene, to see what happens when it is missing and mice over expressing the gene to investigate the consequences of elevated levels of DSCR1 analogous to the situation in Down syndrome.Read moreRead less
The Role Of Dysregulated VEGFs In Lymphatic And Non-lymphatic Vascular Malformations
Funder
National Health and Medical Research Council
Funding Amount
$389,486.00
Summary
Vascular malformations are abnormal growths of blood vessels that affect hundreds of children born in Australia every year. They range from small birthmarks to large destructive growths that cause chronic pain, bleeding and major deformity. This is the largest ever study to systematically look for the biological drivers that cause these growths so that drug treatments will ultimately be able to replace surgery as the first line treatment.
A Randomised Trial Of Core Cooling Versus Surface Cooling In Comatose Survivors Of Prehospital Cardiac Arrest
Funder
National Health and Medical Research Council
Funding Amount
$309,000.00
Summary
Pre-hospital sudden cardiac arrest (SCA) is a major public health problem that is estimated to cause around one death per thousand adults per year. The aetiology of SCA is usually ischaemic heart disease causing ventricular fibrillation (VF). The current medical response to this condition involves a Chain of Survival, including early call to 000, bystander CPR, early defibrillation and early advanced cardiac life support. Following successful cardiac resuscitation, patients are transported to ho ....Pre-hospital sudden cardiac arrest (SCA) is a major public health problem that is estimated to cause around one death per thousand adults per year. The aetiology of SCA is usually ischaemic heart disease causing ventricular fibrillation (VF). The current medical response to this condition involves a Chain of Survival, including early call to 000, bystander CPR, early defibrillation and early advanced cardiac life support. Following successful cardiac resuscitation, patients are transported to hospital for further care. Despite this approach and recent improvements such as decreased ambulance response times, outcome remains poor and there are very few survivors who make a good recovery. This proposal is for funding to conduct a randomised, controlled trial, which compares two different techniques of induction of hypothermia in patients who are resuscitated from pre-hospital sudden cardiac arrest. Recently available data suggests that the outcome from SCA is significantly improved if moderate hypothermia is used as a treatment of neurological injury. However, the technique of induction of hypothermia requires further research. This study compares core-cooling using large-volume ice-cold intravenous fluid with the current technique of using ice packs for surface cooling, initiated in the field by ambulance paramedics and continued in hospital for a total of 12 hours. This study has the potential to demonstrate a significant improvement in outcome in a common clinical condition, which currently carries a very high mortality rate. This will be the first trial internationally which assess core versus surface cooling initiated pre-hospital, in SCA patients. It is highly likely that with the successful results from this trial that induced hypothermia in SCA patients will become standard care. The use of induced hypothermia could lead to over 500 lives saved per year accross Australia.Read moreRead less
Pharmacological Preconditioning And Sodium/hydrogen Exchange Inhibition To Optimise Preservation Of The Donor Pig Heart
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
Heart transplantation has become established as an extremely beneficial treatment for patients with end-stage heart failure, however its success is limited by the restricted availability of donor hearts. Many hearts that could be considered for heart transplantation cannot be used because of damage that can occur to potential donor hearts after the death of the donor. This damage is caused in part by deterioration in heart function after death and in part by the process of removal and cold stora ....Heart transplantation has become established as an extremely beneficial treatment for patients with end-stage heart failure, however its success is limited by the restricted availability of donor hearts. Many hearts that could be considered for heart transplantation cannot be used because of damage that can occur to potential donor hearts after the death of the donor. This damage is caused in part by deterioration in heart function after death and in part by the process of removal and cold storage that occur prior to transplantation of the heart. This study will examine two new methods of optimising the quality and preservation of the donor heart for transplantation. The treatments to be investigated in this study are aimed at preventing damage to the donor heart after death and during the process of transplantation. The studies will be conducted in a pig model of heart transplantation that we have developed in our laboratory. The treatments will be administered to the donor pig after induction of brain death and also to the recipient during transplantation of the heart. As the model closely mimics all aspects of human heart transplantation, any positive findings that stem from these studies will be directly applicable to human transplantation. Improved preservation of the donor heart will make the operation safer and will potentially increase the number of hearts that can be used for transplantation. As many donors provide multiple organs for transplantation eg kidneys, liver, lungs and pancreas, the treatments that we are investigating have the potential to improve the recovery of all these organs after transplantation.Read moreRead less
Cardiovascular Reactivity To Stress: Role Of Redox Signalling In The Hypothalamus And Brainstem
Funder
National Health and Medical Research Council
Funding Amount
$606,979.00
Summary
Cardiovascular disease is Australia's greatest health problem. It kills more people than any other disease and affected 3.5 million Australians in 2004-05. More and more evidence suggests a relationship between the risk of cardiovascular disease and mental stress. But more research is needed on how stress contributes to heart disease risk. This project aims to determine the role of harmful molecules, called free oxygen radicals, in brain in mediating effects of stress on cardiovascular system.
Influence Of Superoxide On The Central Cardiovascular Response To Emotional Stress: Cellular And Subcellular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$642,599.00
Summary
Cardiovascular disease is Australia's greatest health problem. It kills more people than any other disease and affected 3.5 million Australians in 2004-05. More and more evidence suggests a relationship between the risk of cardiovascular disease and mental stress. But more research is needed on how stress contributes to heart disease risk. This project aims to determine the role of harmful molecules, called free oxygen radicals, in brain in mediating effects of stress on cardiovascular system.
The Effect Of Smoking On The Exacerbation Of Stroke: Oxidative Stress Involvement And Cerebrovascular Response.
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
This grant addresses whether smoking contributes to the severity of stroke outcome. The studies outlined in this proposal will contribute significantly in our understanding of how smoking contributes to the progression of stroke. The understanding of the involvement of smoking in the progression of stroke will be of great benefit in the development of improved stroke patient management.