Muscle Metabolic Dysfunction
Work during exercise is performed by the muscles. The muscles must extract and metabolize oxygen during exercise to generate the ATP needed for the muscle fibers to contract. Disorders of substrate utilization will result in impaired ability to metabolize oxygen. In contrast to cardiovascular disorders whereby the exercise capacity is limited due to the impaired ability to deliver O2 to the working muscles at a commensurate rate to generate adequate ATP, patients with muscle metabolic dysfunction have adequate O2 supply but are unable to utilize it due to the disruption of the metabolic pathways caused by a variety of etiologies:
Patients with metabolic dysfunction have:
Note that the main difference between heart failure and muscle metabolic dysfunction is ∆VO2/∆WR. This parameter can only be accurately measured on the cycle. Also note that parameters 1, 2 and 3 are low for different reason in heart failure and muscle dysfunction. Heart failure is an extra-cellular disorder and muscle dysfunction is due to intra-cellular disorders.
Reversible causes to consider are hormonal disorders and medications. Certain patients will have an underlying metabolic susceptibility that is worsened on statin therapy that is not related to inflammation (hence CPK’s may be normal but other enzymatic markers of muscle function may be abnormal). Other disease states to consider are connective tissue/rheumatologic conditions and mitochondrial myopathies.