Assessing Efficacy Of Polyfunctional Nanoparticles Engineered For The Delivery Of Multiple Therapeutics In Reduction Of Cardiac Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$317,678.00
Summary
A reduction in heart muscle damage after a heart attack is associated with a reduction in heart failure and an increase in life expectancy. However to date many therapeutic agents are not successful at reducing muscle damage because of difficulty in delivering the drugs to the target site. This project will address these delivery issues by making use of multifunctional nanoparticles which will allow for targeted delivery and release of therapeutics directly to damaged tissue following injury.
Ryanodine Receptor Inhibitors As Therapy For Ca2+ Store Overload Induced Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
This study investigates a new therapeutic action recently discovered for flecainide, an antiarrhythmic agent that we find to completely prevent and inherited form of stress-induced arrhythmias called CPVT. The findings will provide the first detailed mechanistic understanding of an antiarrhythmic drug, findings that will also give a new direction for drug design to control common arrhythmias such as occur in diseases such as coronary artery disease.
Effects Of Hypoxia And Reactive Oxygen Species On Neuronal Excitability Of Intrinsic Cardiac Ganglia
Funder
National Health and Medical Research Council
Funding Amount
$70,000.00
Summary
Neural control of the heart is mediated by intrinsic cardiac neurones which respond to chemical substances such as neurotransmitters released from nerve fibres innervating the heart and vasoactive substances released into the coronary ciruculation. Prolonged periods of myocardial ischaemia (hypoxia) and post ischaemic reperfusion (oxygen-derived free radicals) influence the electrical activity of the intrinsic cardiac nervous system. The involvement of membrane electrical phenomena in general, a ....Neural control of the heart is mediated by intrinsic cardiac neurones which respond to chemical substances such as neurotransmitters released from nerve fibres innervating the heart and vasoactive substances released into the coronary ciruculation. Prolonged periods of myocardial ischaemia (hypoxia) and post ischaemic reperfusion (oxygen-derived free radicals) influence the electrical activity of the intrinsic cardiac nervous system. The involvement of membrane electrical phenomena in general, and ion-selective pores (ion channels) in particular, and the action of hypoxia and oxygen-derived free readicals on their function will be studied in isolated neurones dissociated from neonatal and adult rat intrinsic cardiac ganglia. The characterization of ion channels modulated by hypoxia and reactive oxygen species will be monitored using electrical and fluorescence techniques. The opening of ion channels in the cell membrane by changes in either voltage or the intracellular calcium ion concentration leads to an electrical response. The goal of the research is to elucidate the mechanisms underlying the effects of ischaemia and ischaemia-reperfusion on neuronal excitability in mammalian cardiac ganglia, thus regulation of the heart rate. Development of therapeutic strategies to prevent ischaemia and reperfusion injuries in coronary heart disease and improvement of cardiac protection during surgery are potential outcomes of this research.Read moreRead less
Enkephalin Metabolism In Cardiac Ischemia, Heart Failure And Cardiac Surgery
Funder
National Health and Medical Research Council
Funding Amount
$327,037.00
Summary
It has recently been discovered in animal studies that heart muscle can make its own opioid proteins. Previously, it was thought that only nerves made and released opioids. We have recently found that a class of opioids called enkephalins are made and then depleted from the heart during the stress of oxygen and nutrient deprivation. Enkephalins have been found to have potent metabolic effects on the heart. Previous work has shown that opioids can protect the heart against injury incurred during ....It has recently been discovered in animal studies that heart muscle can make its own opioid proteins. Previously, it was thought that only nerves made and released opioids. We have recently found that a class of opioids called enkephalins are made and then depleted from the heart during the stress of oxygen and nutrient deprivation. Enkephalins have been found to have potent metabolic effects on the heart. Previous work has shown that opioids can protect the heart against injury incurred during disease that restricts energy and oxygen supply to the blood vessels and heart. We wish to demonstrate this for the first time in human heart, and we will explore whether the production of enkephalins is altered by the stresses of cardiac surgery and heart failure. Understanding how the human heart attempts to protect itself in disease and how enkephalins work under these conditions, may prove valuable in the development of new drug therapy with synthetic drugs which mimic the action of enkephalins for heart protection during cardiac surgery, heart transplantation and ischemic heart disease. We will test whether specific enkephalins may be used to improve donor heart viability for transplantation by improving the duration and quality of preservation during storage. Understanding what happens to enkephalin production and metabolism in the failing hearts of patients may allow us to find new therapeutic targets in heart failure.Read moreRead less
Development Of A First-in-class Therapeutic For Protecting The Ischemic Heart
Funder
National Health and Medical Research Council
Funding Amount
$926,673.00
Summary
Heart disease is the leading cause of death globally. Heart attacks are the primary cause of death associated with heart disease. We have discovered a drug, Hi1a, that blocks the injury response of the heart when a heart attack happens. There are no other drugs currently available or in the discovery pipeline that address this problem. This proposal will use models of injury to the heart as well as safety studies to help develop Hi1a as a new drug for people who suffer from heart attacks.
Regulation Of The Cardiac Sodium/proton Exchanger During Ischaemia, Reperfusion And Preconditioning
Funder
National Health and Medical Research Council
Funding Amount
$101,000.00
Summary
Heart attacks are currently treated with drugs to dissolve the clot in the coronary artery or by catheterisation with the aim of restoring blood flow to the ischaemic heart muscle. If restoration of blood flow occurs soon after the heart attack, the ischaemic region can recover completely. However if treatment is delayed, the ischaemic region may not recover. This project concerns the mechanisms that are involved in the myocardial damage which occurs after moderate periods of ischaemia. A transp ....Heart attacks are currently treated with drugs to dissolve the clot in the coronary artery or by catheterisation with the aim of restoring blood flow to the ischaemic heart muscle. If restoration of blood flow occurs soon after the heart attack, the ischaemic region can recover completely. However if treatment is delayed, the ischaemic region may not recover. This project concerns the mechanisms that are involved in the myocardial damage which occurs after moderate periods of ischaemia. A transport protein, the sodium-proton exchanger, is involved in recovery and if its action is blocked with an inhibitory drug, recovery of the ischaemic myocardium is improved. However clinical trials of the drug in humans have given variable results. We are investigating the regulation of this exchanger and believe that such information is essential to the efficient use of the inhibitory drugs in humans and may identify other pathways to improving recovery after ischaemia.Read moreRead less