417PA pilot study to explore a non-invasive measure of mitochondrial dysfunction

Abstract

Grip strength is a simple and inexpensive clinical test. However, by limiting measurement to the force of an isolated contraction, we are missing functionally, and mechanistically relevant information. Skeletal muscle ATP consumption can increase 100-fold with exercise and the majority of this ATP is generated in mitochondria by oxidative phosphorylation. Therefore, repeated intermittent contraction may be more likely to detect underlying mitochondrial dysfunction. Near-infra-red spectroscopy (NIRs) has been used to detect mitochondrial dysfunction previously. Combining NIRs of the forearm muscles with a handgrip exercise protocol may provide a non-invasive measure of mitochondrial function. To explore whether a handgrip exercise protocol with continuous force and NIRs measurement can reliably distinguish mitochondrial myopathy patients from age and sex-matched controls. We used a 3-minute handgrip exercise protocol (squeeze 1 second at 40% maximal voluntary contraction, relax 1 second). We combined this with continuous force measurement using a digital dynamometer with a sampling frequency of 200Hz and Artinis Portamon Near-Infra Red Spectroscopy (NIRs). We compared 10 people with genetic mitochondrial myopathy and exercise intolerance with 20 age and sex-matched healthy controls. Force and NIRs measurements were combined and analysed in a specifically designed Matlab app. Initial analysis shows the total force (area under curve) over a 3-minute handgrip exercise protocol was significantly and consistently less in patients with genetically confirmed mitochondrial disease. The forearm flexor compartment NIRs Tissue Saturation Index (TSI) was not significantly different between groups. However, NIRs effect appeared to vary significantly between patients. The ‘total’ force after 3 minutes of a hand-grip exercise protocol may be a useful biomarker in mitochondrial disease. Although there was no significant group difference in NIRs TSI between people with genetically confirmed mitochondrial disease and healthy controls, there was a subset of mitochondrial patients who exhibited minimal change in TSI over the forearm exercise test (Figure 9). Exploratory analysis on the link between genotype, phenotype and NIRs response profile will be performed.

Publication
Neuromuscular Disorders

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