Reduced Ischaemic Tolerance In The Aged Myocardium: The Role Of Adenosine And Adenosine Receptors
Funder
National Health and Medical Research Council
Funding Amount
$470,250.00
Summary
Despite a decline in deaths rates due to heart disease over the last decade, cardiovascular disease remains the single greatest cause of premature death in individuals over 65 years of age. It accounts for a major and increasing portion of health care costs. Coronary artery disease affects 50% of those older than 65, and with the ageing of our population it is estimated that the elderly population will nearly double from 13-14% to 25% over the next 30 years. Unfortunately, it appears that the ag ....Despite a decline in deaths rates due to heart disease over the last decade, cardiovascular disease remains the single greatest cause of premature death in individuals over 65 years of age. It accounts for a major and increasing portion of health care costs. Coronary artery disease affects 50% of those older than 65, and with the ageing of our population it is estimated that the elderly population will nearly double from 13-14% to 25% over the next 30 years. Unfortunately, it appears that the aged heart is less resistant to disease and injury, contributing to the increase in mortality with ageing. The reasons are not known. This research project will attempt to identify molecular changes which occur in the heart during ageing which may lead to a decline in ability to withstand disease and injury. The research will specifically examine the possibility that a key protective response, known as the adenosine receptor system, is somehow impaired or abnormal in the cells of the aged heart. If it is found that this process is impaired, the research will attempt to rectify this abnormality using new genetic therapy techniques to switch on the heart's own intrinsic defense mechanisms. This may ultimately open up new avenues for specific therapeutic approaches to treatment of ischaemic heart disease in the elderly.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
Iron And Oxidative Stress In Stable And Unstable Coronary Artery Disease
Funder
National Health and Medical Research Council
Funding Amount
$86,570.00
Summary
This PhD investigates the key roles iron and insufficient antioxidants play in worsening tissue injury during and following a heart attack, in precipitating blockages in heart arteries, and in impairing blood vessel function in those with heart disease. By using drugs to remove iron from the body, it is possible to compare the detrimental effects of iron (on tissue injury and blood vessel function) in the group treated with the medication and the group treated with placebo.
I am a cardiac pharmacologist investigating new therapies for the precursors of, and preventing their transition to, heart failure. My core activities focus on factors that control cardiac hypertrophy and ventricular function, in both the absence and pres
The Role Of Glutathionylation In Redox Modification Of L-type Ca2+ Channel Function During Oxidative Stress In The Heart
Funder
National Health and Medical Research Council
Funding Amount
$402,898.00
Summary
The L-type calcium channel is a protein in the membrane of heart muscle cells responsible for regulating the entry of calcium into cells and maintaining normal heart rhythm and contraction. We have shown that reactive oxygen species can regulate the function of the calcium channel. We are now interested in determining whether a direct modification of the channel protein known as glutathionylation is responsible for altered channel function during oxidative stress such as after a heart attack.
Towards A New Normokalemic Arrest Paradigm For Orthotopic Heart Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$489,634.00
Summary
Innovations from Nature to Heart Transplantation:a Real Heart Stopper Heart preservation is limited to 4-6 hours of cold-ischaemic storage (0 to 4 C). The risk of post-transplant death doubles if the donor heart is stored from 1 to 5 hours, and triples with 7 hrs storage times. We have developed a new preservation solution borrowing from natural hibernators that will permit organs to be safely stored for up to 15 hours, and offering new opportunities to organ donors and recipients worldwide.
Adenosine A1 And A3 Receptor Mediated Cardioprotection In Ischaemic Myocardium
Funder
National Health and Medical Research Council
Funding Amount
$265,698.00
Summary
Damage to the heart from coronary vascular disease causes significant morbidity and mortality in Australia. Indeed, ischaemic injury represents the single greatest cause of premature death. Moreover, due to the increasing age of our population the problem is growing - coronary artery disease affects 50% of those older than 65, contributing to an increased incidence of angina pectoris, myocardial infarction, arrhythmia, congestive heart failure, and sudden death. Protective strategies have been, ....Damage to the heart from coronary vascular disease causes significant morbidity and mortality in Australia. Indeed, ischaemic injury represents the single greatest cause of premature death. Moreover, due to the increasing age of our population the problem is growing - coronary artery disease affects 50% of those older than 65, contributing to an increased incidence of angina pectoris, myocardial infarction, arrhythmia, congestive heart failure, and sudden death. Protective strategies have been, and continue to be, developed to reduce the extent of tissue damage and minimise prolonged reductions in heart function. The success of these interventions has been mixed. This research project takes the novel approach of identifying the true roles of two receptors present in the heart (the adenosine A1 and A3 receptors) which may play a crucial role in enhancing tolerance of the heart to disease and injury. We currently do not fully understand the roles of these receptors, although preliminary findings suggest they can exert powerful protective effects during disease conditions. From a fundamental viewpoint, identifying the roles of these two receptors will significantly advance our understanding of the mechanisms of injury and protection in the heart. From a therapeutic viewpoint, this study will take us closer to the potential use of adenosine receptor-based therapy in protecting the heart from ischaemic injury.Read moreRead less
The Importance Of P38 MAPK Signalling In Aging-Related Ischaemic Intolerance And Failed Cardioprotection
Funder
National Health and Medical Research Council
Funding Amount
$496,302.00
Summary
Ischaemic heart disease is the leading cause of death in Australia, and will rise in coming years with the aging of our population. Our research shows aged hearts become less resistant to damage during ischaemia-heart attack, and insensitive to normally beneficial therapies. This project will identify molecular changes responsible for these changes. By understanding how age impairs the hearts defences, it may be possible to improve therapy of ischaemic heart disease in older patients.
Development Of Recombinant RsolCD39-PSGL As A Novel Therapeutic With Anti-thrombotic And Anti-inflammatory Effects
Funder
National Health and Medical Research Council
Funding Amount
$186,367.00
Summary
Heart disease and stroke are due to a narrowing of arteries followed by occlusion, due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. The currently available drugs are often limited by the adverse reaction of bleeding. We will investigate the efficiency of a new drug to prevent clot formation and inflammation.