What Central Mechanisms Increase Cardiac Sympathetic Nerve Activity In Heart Failure?
Funder
National Health and Medical Research Council
Funding Amount
$401,389.00
Summary
Heart failure is a disabling and deadly syndrome that has reached epidemic proportions in western populations. In heart failure, the activity of the sympathetic nerves to the heart is dramatically increased, leading to development of arrhythmias and sudden death. Using our unique model of heart failure, in which we directly record cardiac sympathetic nerve activity, we aim to determine the mechanisms in the brain that cause this large, detrimental increase in nerve activity.
Although the heart contracts spontaneously, the rate and force with which it beats may be modified by the autonomic nervous system. That is, the rate and force of heart muscle contraction may be increased or decreased by the activation of two different sets of nerves. This project will determine how the autonomic nervous system modifies the strength of heart muscle contraction. It will involve the measurement of changes in contractile force, electrical activity and calcium levels within cardiac ....Although the heart contracts spontaneously, the rate and force with which it beats may be modified by the autonomic nervous system. That is, the rate and force of heart muscle contraction may be increased or decreased by the activation of two different sets of nerves. This project will determine how the autonomic nervous system modifies the strength of heart muscle contraction. It will involve the measurement of changes in contractile force, electrical activity and calcium levels within cardiac cells during muscle contraction. The effects of excitatory and inhibitory nerve stimulation on these three parameters will be examined. Results of this study will improve our understanding of how the contraction of heart muscle is controlled and provide an insight into the treatment of heart disease.Read moreRead less
Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which w ....Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which we have shown to operate in various smooth muscles. This mechanism, termed store-based pacemaking, is entirely different to the currently held cardiac model but could readily achieve the same outcome. We will investigate the hypothesis that this pacemaker mechanism is also fundamental to heart pacemaking and conduction. Positive support for our hypothesis, as indicated by our pilot findings, may severely challenge the present model for cardiac pacemaking. Such an outcome will have major ramifications on present interpretation of cardiac function in health and disease and will be particularly important to interpretation of disorders associated with cardiac arrhythmias and heart conduction.Read moreRead less
Cardiac Sympathetic Nerve Activity: Understanding Normal Control And The Causes Of The Increase In Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$531,125.00
Summary
Heart failure is a condition in which the heart muscle becomes weak and is unable to pump sufficient blood around the body to provide adequate perfusion of the organs. This results in breathlessness, lethargy, fatigue, mental confusion and eventually death. At present the life expectancy of patients with heart failure is poor, with a 5 year survival of 25% in men and 38% in women. It is the only form of heart disease that is increasing, the reason being that thousands of patients who have surviv ....Heart failure is a condition in which the heart muscle becomes weak and is unable to pump sufficient blood around the body to provide adequate perfusion of the organs. This results in breathlessness, lethargy, fatigue, mental confusion and eventually death. At present the life expectancy of patients with heart failure is poor, with a 5 year survival of 25% in men and 38% in women. It is the only form of heart disease that is increasing, the reason being that thousands of patients who have survived heart attacks or had coronary bypass operations go on to develop heart failure. In heart failure there is a very large increase in the activity of the nerves that stimulate cardiac rate and contractility, the cardiac sympathetic nerves. This increase in activity is detrimental, higher levels of activity predict greater morbidity and a reduced life span. The mechanisms causing the increase in cardiac sympathetic nerve activity are unknown, but greater understanding is essential if new and improved treatments are to be developed for patients with heart failure. Only two groups in the world measure cardiac nerve activity in conscious animals, neither is studying heart failure. We therefore have a unique opportunity to investigate the factors that control the activity of the cardiac nerves in the healthy state and to establish the causes of the increase in activity in heart failure. In particular, we will investigate how reflex control mechanisms, circulating hormones that are increased in heart failure and specific mechanisms in the brain act to control cardiac nerve activity in the normal state and what changes in these mechanisms lead to the preferential increase in cardiac nerve activity in heart failure. These findings will provide a detailed understanding of the mechanisms controlling cardiac nerve activity in the normal healthy state and increased knowledge of the factors that lead to the preferential activation of the cardiac nerves in heart failure.Read moreRead less
CENTRAL BLOCKADE OF SYMPATHETIC RESPONSES TO EMOTIONAL STRESSORS
Funder
National Health and Medical Research Council
Funding Amount
$313,933.00
Summary
Emotional stress triggers physiological reactions that affect our heart and blood pressure. For people with a weak or failing heart, this can lead to stroke and death. This project explores the effects and the sites of action in the brain of two different types drugs that could potentially reduce or prevent such accidents. Unlike the drugs that are currently in use, these two drugs act directly in the parts of the brain that control cardiovascular responses to emotional stress.