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
Does Aerobic Or Resistance Training Improve Walking Ability In Chronic Stroke Patients?
Funder
National Health and Medical Research Council
Funding Amount
$152,036.00
Summary
The majority of stroke patients discharged from rehabilitation are often housebound. The criterion which most often limits individuals with stroke from achieving 'community ambulation' is the inability to walk long distances. Current views suggest that an exercise program aimed at improving lower limb strength and aerobic fitness will improve walking ability in those stroke patients with mild to moderate disability. However, there are no reported studies that have rigorously investigated whether ....The majority of stroke patients discharged from rehabilitation are often housebound. The criterion which most often limits individuals with stroke from achieving 'community ambulation' is the inability to walk long distances. Current views suggest that an exercise program aimed at improving lower limb strength and aerobic fitness will improve walking ability in those stroke patients with mild to moderate disability. However, there are no reported studies that have rigorously investigated whether either of these approaches, singularly or combined, is effective for augmenting walking ability in chronic stroke patients. We will use a randomised, double-blinded controlled trial to determine which of strength training, aerobic training or a combination of the two is the most effective approach for improving walking endurance, measured by the 6-minute walk test, in individuals with mild-to-moderate stroke. In addition, we will determine the benefits of each program to subjects' cardiorespiratory fitness, lower limb strength, mobility and psychological function. Subjects will be randomly allocated to one of 4 groups: 1) Aerobic exercise (and sham strength training); 2); Strength training (and sham aerobic training); 3) Combined strength and aerobic training; and 4) Control (sham strength and aerobic training. Sham treatment for strength training is stretching and calisthenics, and for aerobic exercise is passive motorised cycling. All subjects will attend small group sessions for 10 weeks, with 3 sessions per week, and each session about 1 hour duration. The findings from this study are critical in identifying the most effective and efficient approach to improving stroke patient's walking endurance. Improvement in walking endurance will enable many persons following stroke to achieve the level of 'community ambulation'. Last, it will contribute to the 'evidence-based' scientific framework for treatment of stroke patients.Read moreRead less
Does Manipulation Of Arterial Shear Stress Enhance Cerebrovascular Function And Cognition In The Aging Brain?
Funder
National Health and Medical Research Council
Funding Amount
$707,914.00
Summary
Globally, 9.2 million less cases of dementia could result from delaying it by as little as 12 months. We will assess the impact, on artery health and cognition, of a novel exercise intervention involving enhanced patterns of brain blood flow and arterial shear stress during exercise, stimuli which should optimise cerebrovascular health. Given that pharmacological approaches to prevention are ineffective, this project has the potential to address the future impact of this common and debilitating ....Globally, 9.2 million less cases of dementia could result from delaying it by as little as 12 months. We will assess the impact, on artery health and cognition, of a novel exercise intervention involving enhanced patterns of brain blood flow and arterial shear stress during exercise, stimuli which should optimise cerebrovascular health. Given that pharmacological approaches to prevention are ineffective, this project has the potential to address the future impact of this common and debilitating disease in Australians.Read moreRead less
Discovering And Targeting Genes Regulating Skeletal Muscle Function, Metabolism, And Adaptations To Exercise Interventions
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Muscle wasting and decreased in mitochondrial function due to ageing or lack of physical activity are associated with reduced quality of life. The overarching aim is to develop a unique research program focusing on targeting specific genes, and to discover novel genes regulating muscle wasting and mitochondrial (dis)function. I anticipate this approach to assist in the development of targeted and personalised prevention and therapy for diseases associated with muscle (dis)function.
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.
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
Exercise Cardiac Imaging To Study Right Ventricular Functional Remodelling In Athletes With And Without Ventricular Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$392,587.00
Summary
Extreme exercise results in heart remodelling for which the long-term consequences are incompletely understood. We have described transient reductions in heart function following endurance sport. However, we have also described a group of athletes with serious heart rhythm problems and sustained right heart abnormalities. Therefore, we hypothesize that extreme exercise can cause potentially serious heart changes in some athletes and that detailed heart assessment during exercise will predict tho ....Extreme exercise results in heart remodelling for which the long-term consequences are incompletely understood. We have described transient reductions in heart function following endurance sport. However, we have also described a group of athletes with serious heart rhythm problems and sustained right heart abnormalities. Therefore, we hypothesize that extreme exercise can cause potentially serious heart changes in some athletes and that detailed heart assessment during exercise will predict those at greatest risk.Read moreRead less