Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
Understanding The Metabolic Consequences Of Impaired AMPKa2 And NNOS� In Skeletal Muscle: Implications For The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$575,527.00
Summary
The inability of muscle to utilise sugar from the blood is a major problem that contributes to obesity and Type 2 diabetes. Since the number of people with these diseases will at least double by 2030, we need to find out what causes this problem. We will examine whether two muscle proteins that are impaired in obesity and Type 2 diabetes are also responsible for impaired sugar utilisation. We think that increasing these muscle proteins will fix the _sugar problem�, and remedy these diseases.
The Role Of Nitric Oxide In The Regulation Of Skeletal Muscle Glucose Uptake During Exercise
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participa ....When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participate in blood flow, nerve transmission and immune function, appears to be a necessary component for muscle glucose uptake at rest and during exercise. We have shown that blocking muscle NO production substantially reduces leg glucose uptake during exercise. The aim of this project is to verify this finding and to determine the mechanisms underlying this result. One way we intend to do this is to see whether a drug (Viagra) which increases the effects of NO, raises muscle glucose uptake at rest and during exercise. In rats, a drug almost identical to Viagra stimulates muscle glucose uptake. If Viagra is shown to increase glucose uptake this information may provide the initial human data necessary to develop new drugs to lower blood glucose levels in people with diabetes.Read moreRead less
Improving Functional Capacity In Patients With Chronic Lung Disease With High Intensity Respiratory Muscle Training
Funder
National Health and Medical Research Council
Funding Amount
$340,880.00
Summary
Patients with chronic respiratory disease have limited exercise capacity, which severely impairs their quality of life. The mechanisms responsible for this impairment may relate to their lung disease, or to the long-term effects that inactivity has on the cardiovascular and musculoskeletal systems. Pulmonary rehabilitation programs involving whole-body exercise are now widely used as an addition to standard medical therapy as a way of decreasing symptoms and optimising function. While these gene ....Patients with chronic respiratory disease have limited exercise capacity, which severely impairs their quality of life. The mechanisms responsible for this impairment may relate to their lung disease, or to the long-term effects that inactivity has on the cardiovascular and musculoskeletal systems. Pulmonary rehabilitation programs involving whole-body exercise are now widely used as an addition to standard medical therapy as a way of decreasing symptoms and optimising function. While these generalised, broad-based programs result in modest improvements in peripheral muscle function, cardiovascular function, functional exercise capacity and quality of life, it is now apparent they have little or no effect on respiratory muscle function, which is also greatly impaired in COPD. The aims of this study are to answer two longstanding questions that are fundamental to rehabilitation programs in patients with COPD (i) does a program of specific respiratory muscle training alone improve whole-body exercise capacity, dyspnoea, and-or quality of life? and (ii) does the addition of a program of specific respiratory muscle training to a standard whole-body exercise rehabilitation program result in improvemed exercise capacity, dyspnoea and-or quality of life to a greater degree than a program of whole-body exercise training alone? The study is of importance to patients with COPD by investigating the mechanisms underlying the improvement in exercise capacity following a rehabilitation program and the role of respiratory muscle training in such a program. By more accurately defining the mechanisms of exercise limitation we may be able to maximise the benefits obtained during a rehabilitation program, including improved work capacity, reduction in the degree of breathlessness and improved quality of life.Read moreRead less
Developing A Standard Dyspnea Challenge To Explore Mechanisms And Therapies In Clinical Populations
Funder
National Health and Medical Research Council
Funding Amount
$454,383.00
Summary
COPD is Australia's most burdensome respiratory disease with over 200,000 new cases diagnosed each year. Shortness of breath is a cardinal feature of this disease.This project will examine the mechanisms of this symptom in patients with chronic lung disease. Four studies will be completed in total, each exploring different factors that may contribute to shortness of breath observed in patients. This research is likely to lead to improved management of this distressing condition into the future.
Efficacy And Mechanisms Of Exercise Training In Diastolic Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$385,250.00
Summary
Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrom ....Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrome is most frequently due to ischemic or hypertensive heart disease, and most commonly occurs in the elderly. The optimal management of DHF is not well defined, although some drug trials are currently in progress. A number of studies have shown exercise training to improve functional capacity by 15-20% in typical heart failure. However, training has not so far been trialled in DHF. In this multicenter, multi-disciplinary study, we will study a training and control group to determine whether exercise capacity and DHF symptoms are responsive to exercise training. This work will teach us about the optimum exercise prescription, in terms of the duration and nature of training, as well as the safety and effectiveness of exercise training. By using a number of sensitive measurements of heart and vessel function (in which our group has special expertise), we will identify whether exercise training exerts its effect through improvement in vascular function and myocardial properties. If successful, the clinical implications of this study are that; 1. Exercise training will be adopted to improve functional capacity and symptoms of DHF 2. The merits of aerobic and strength training will be identified in DHF 3. Abnormal blood vessel function will be identified as a major and reversible contributor to DHFRead moreRead less
Improving Muscle Function After Injury: Novel Tissue Engineering Strategies For Exercise, Surgery And Sports Medicine
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Muscles can be injured by excessive strains when playing sports, in road and workplace accidents, and during plastic and reconstructive surgery. Some surgeries require an unavoidable interruption to the muscle's normal blood supply (called 'ischaemia'). Subsequent return of the muscle's blood supply (reperfusion) is problematic in that a severe secondary muscle injury can ensue mediated by the influx of damaging free radicals when blood flow is restored. Tissue-engineering provides a novel thera ....Muscles can be injured by excessive strains when playing sports, in road and workplace accidents, and during plastic and reconstructive surgery. Some surgeries require an unavoidable interruption to the muscle's normal blood supply (called 'ischaemia'). Subsequent return of the muscle's blood supply (reperfusion) is problematic in that a severe secondary muscle injury can ensue mediated by the influx of damaging free radicals when blood flow is restored. Tissue-engineering provides a novel therapeutic approach to restore muscle structure and function to damaged muscles after injury or disease. Our recent research using controlled release of growth factors from biodegradable hydrogels has exciting application for muscle repairafter injury. We will utilize these cutting edge tissue engineering strategies to deliver to damaged muscles a hydrogel containing controlled delivery (slow release) microcapsules loaded with an anabolic agent (the beta-agonist, formoterol) and-or a growth factor (IL-15) designed to enhance functional muscle repair after three distinct but clinically relevant models of muscle injury: a) crush injury: A model for muscle injuries on the sports field, in the workplace, and those associated with road trauma; b) ischaemia-reperfusion injury: a model for muscle damage associated with surgical interventions, muscle transfers for functional restoration, and other injuries associated with plastic and reconstructive surgery; and c) contraction-induced injury: a model for strain injuries such as hamstring muscle tears that can occur on the sports field. After injury we will assess functional muscle repair using a comprehensive series of histological, biochemical, molecular, immunochistochemical, and physiological techniques. The research has broad application to exercise and clinical medicine; including sports, emergency and rehabilitation medicine, and plastic, reconstructive, and orthopaedic surgery.Read moreRead less
Targeted Strength Training To Improve Functional Walking Capacity Of Adolescents And Young Adults With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$263,449.00
Summary
Cerebral palsy is the most common cause of disability in children. Caused by damage to the brain in early childhood cerebral palsy leads to muscle weakness and difficulties in walking. There is no cure for cerebral palsy, but we can help the weak muscles . The purpose of this trial is to establish that exercises to strengthen the weakest muscles will help the walking ability of teenagers and young adults with cerebral palsy, as they make the transition to independence and adulthood.
The Effects Of A Two Year Randomised Exercise Intervention On Markers Of Bone Turnover In Postmenopausal Women
Funder
National Health and Medical Research Council
Funding Amount
$43,573.00
Summary
Osteoporosis is a condition where the bones become more fragile and can break more easily. In Australia after age 60, three out of every five women and three out of every ten men will fracture a bone. When people fracture a hip they lose their independence and become much less mobile. Exercise is one lifestyle approach which may help in preventing osteoporosis by slowing bone loss and keeping the muscles strong. Previous research has not been able to clearly demonstrate the usefulness of exercis ....Osteoporosis is a condition where the bones become more fragile and can break more easily. In Australia after age 60, three out of every five women and three out of every ten men will fracture a bone. When people fracture a hip they lose their independence and become much less mobile. Exercise is one lifestyle approach which may help in preventing osteoporosis by slowing bone loss and keeping the muscles strong. Previous research has not been able to clearly demonstrate the usefulness of exercise due partly to the difficulty in getting people to exercise for a least one year, which is how long bone studies must be carried out for. We have conducted two large research studies in women past the menopause where they have done weight training exercises. In the previous study we showed the greatest increase in bone mass occurred in those women lifting the heaviest weights. In a recently completed two year study in 126 woman, which forms the basis of this proposal, we found a weight training program was effective at increasing the bone mass at the hip, a common fracture site. The fitness group did not show any increase. So although we have been able to show this type of exercise helps increase bone mass we don't know how the bone is able to respond to this. The question we wish to address with this proposal is does exercise slow the breakdown of bone or does it help form new bone? The best way to be able to answer this question is by measuring certain products in blood, known as bone markers. Bone is continually turning overthese markers are released from bone into the blood. By studying these bone markers in blood samples taken from the subjects over two years it will helps us determine how exercise is affecting bone. From our previous studies we know that weight training can help slow bone loss. By measuring the bone markers we will then be able to make recommendations to people on how exercise will help prevent bone loss.Read moreRead less