This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Our objective is to examine the effects of the drug dichloroacetate on aerobic function and maximal work capacity in patients with CLA. We will recruit 10 individuals with documented disease to comprise our patient cohort. We will enroll age and gender matched cohort of healthy volunteers as normal comparison group. This investigation will employ two experimental conditions to test specific hypotheses. We will examine the effect of DCA on lactate kinetics, maximal oxygen uptake (VO2 max) and maximal work capacity during graded exercise on a cycle ergometer in patients with CLA. Patients will perform a graded exercise test to voluntary maximal exertion on a cycle ergometer while treated with either DCA or placebo. We hypothesize that DCA treatment will significantly increase the VO2 at the individual lactate threshold in patients with CLA. In experiment 2, we will examine the effect of DCA treatment on lactate production, substrate utilization, and hemodynamic responses to submaximal exercise in patients with CLA. Patients will perform a 15-minute exercise bout at an intensity designed to elicit 80% of the VO2 at LT. We hypothesize patients with CLA will demonstrate reduced levels of lactic acid, increased rates of carbohydrate oxidation, increased cardiac and ventilatory efficiency, and decreased ratings of perceived exertion; during a submaximal exercise bout prescribed at a level related to their individual LT. Finally, we will compare the exercise responses under these two experimental conditions to a cohort of healthy volunteers, adjusting for age and sex, not treated with either DCA or placebo.
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