1. Muscle metabolism and dysfunction in obesity. The HISTORY STUDY.
Our CIHR Team Grant is funding research that is investigating muscle metabolism in obesity. We are conducting MRI and MRS investigations on the pathophysiology of childhood obesity on muscle metabolism. As part of this research, we have developed several powerful MRI techniques to investigate intramyocellular lipids as well as adiposity in other tissues such as the liver. This has allowed us to expand our previously developed 31P-MRS muscle metabolism testing, and we are investigating the relationships between lipid and muscle metabolism, with some excellent preliminary results, thus far. Our current research in this area is an extension of previously completed investigations on patients with Craniopharyngioma and Turners Syndrome.
2. Muscle metabolic dysfunction in respiratory disease.
The second series of studies involves ongoing research on muscle metabolic dysfunction in patients with respiratory disease. We are applying a new MRI technique to investigate the effects of systemic inflammation on perfusion in muscle of patients with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD). The new technique uses traditional blood oxygen level dependent imaging (BOLD fMRI) in combination with exercise to evaluate muscle blood perfusion and oxygenation. When combined with 31P-MRS measurement of mitochondrial metabolism, we are able to examine the oxygen transport capabilities and limitations of the muscles of children with chronic diseases. We have some intriguing preliminary results that suggest differences in blood flow and oxygenation in children with PCD versus those with CF and healthy controls. This research has been previously supported by the Canadian Cystic Fibrosis Foundation.
3. Remote ischemic preconditioning.
We are conducting a series of studies investigating the effects of remote ischemic preconditioning (RIPC) in both elite adolescent athletes and age matched healthy controls. We are using BOLD MRI and 31P-MRS techniques to investigate the mechanism of action of this therapy. Concurrently, we used our BOLD fMRI and 31P-MRS techniques to evaluate the impact of RIPC in muscle tissue during and after exercise. These preliminary data led to a successful CIHR grant application to monitor the effects of longer-term exposure to RIPC compared to an exercise stimulus. Although the primary objective of this study is to examine peripheral muscle dysfunction, we are attempting a new technique – 31P-MRS measurement of cardiac muscle, which is ground breaking and challenging, and considered to be the “holy grail” of MRS measurement.
4. Mitochondrial disease
We are applying our 31P-MRS muscle metabolism testing, in conjunction with a standardized exercise protocol as a clinical diagnostic tool in patients with inborn errors of mitochondrial metabolism. We now have a significant database developed with healthy controls and patients with respiratory disease against which to compare our results. We are hopeful that our non-invasive technology can eventually be used to help clinicians confirm their diagnoses and increase our understanding of the impact of mitochondrial disease on muscle metabolism.
5. Optimizing taper in competitive swimmers.
A critical time of the year for coaches and athletes is the taper phase. It is here that training, preparation, and the season are all put to the test as athletes attempt to improve their performance. The challenge for sport scientists and coaches is to use their knowledge and experience to help the athlete make that final adaptation and reach their potential while adjusting for factors like travel, stress, technique, and physical changes that come with reduced training. Recent research has indicated that the effect of central and peripheral nervous system function and adaptation may be important factors in determining the athlete’s response to training. However, there is little research on the role of the central nervous system adaptation during the taper phase. This research program is designed to evaluate the effectiveness of several methods used to monitor nervous system function during the taper phase and correlate these measures with performance outcomes during competitions.
6. Elucidation of the pathophysiology of exercise intolerance in pediatric patients with ALL
Acute lymphoblastic leukemia (ALL) is the most common type of malignancy diagnosed in children, yet is one of the most treatable cancers, with long-term survival rates approaching 80% 1. As such, considerations for life beyond ALL are important. Survivors of ALL are at risk for becoming overweight as an adult, and the adverse outcomes associated with obesity 3. As well, cancer and cancer treatment results in decreased functional work capacity, flexibility, mobility, and impaired neuromuscular function 2,4>. However, the exact physiological mechanisms that lead to exercise intolerance in children with ALL are unclear. The evidence supporting and informing exercise interventions in children with ALL is weak – therefore, a greater understanding of the pathophysiology and determinants of exercise intolerance are needed. We will conduct a randomized controlled trial that will assess the effects of an exercise intervention post bone marrow transplant (BMT) in children with ALL. We will implement a 6-month, three-arm RCT: children with ALL will be randomized to a non-exercise control group (n=20), a resistance-training group (n=20), or an aerobic exercise group (n=20). We will measure the effects of exercise on multiple outcomes in children with ALL, including biomarkers, muscle strength, neuromuscular function, bone health, and quality of life using traditional and more advanced techniques such as blood oxygen level dependent magnetic resonance imaging (BOLD MRI), arterial spin labeling techniques, and 1Hydrogen- and 31Phosphorus Magnetic Resonance Spectroscopy. Our research findings will be used to inform effective and unique exercise therapeutic interventions in children with ALL, which may improve muscle function, mobility, and potentially attenuate some of the negative physiological consequences experienced by ALL survivors.
7. The effect of omega-3 supplementation on exercise induced neuromuscular fatigue and inflammation
Exercise causes fatigue and inflammation from muscle damage. A source of fatigue during exercise is a decrease in nerve signalling (neural fatigue) that causes muscles to contract. Inflammation caused by exercise can delay recovery and beneficial adaptations to exercise. Omega-3 fatty acids, which are found in fish and nuts, are used to make and maintain nerves throughout the body. Because of this role, it is thought that supplementing with omega-3s will reduce neural fatigue during exercise. Additionally, omega-3s are known for their anti-inflammatory effects. This benefit may help to reduce inflammation after exercise. At this time, the effect of omega-3 supplementation on neural fatigue and inflammation after exercise has not been examined. Therefore, the objective of my research is to determine if taking omega-3 supplements can reduce neural fatigue and decrease inflammation after exercise in healthy participants and children with chronic inflammatory diseases.