Abstract
Muscle biopsies are the gold standard to assess mitochondrial respiration; however, biopsies are not always a feasible approach in persons with spinal cord injury (SCI). Peripheral blood mononuclear cells (PBMCs) and near-infrared spectroscopy (NIRS) may alternatively be predictive of mitochondrial respiration. The purpose of the study was to evaluate whether mitochondrial respiration of PBMCs and NIRS are predictive of respiration of permeabilized muscle fibers after SCI. Twenty-two individuals with chronic complete and incomplete motor SCI between 18-65 years old were recruited to participate in the current trial. Using high-resolution respirometry, mitochondrial respiratory capacity was measured for PBMCs and muscle fibers of the vastus lateralis oxidizing complex I, II, and IV substrates. NIRS was used to assess mitochondrial capacity of the vastus lateralis with serial cuff occlusions and electrical stimulation. Positive relationships were observed between PBMC and permeabilized muscle fibers for mitochondrial complex IV (r = 0.86, P < 0.0001). Bland-Altman displayed agreement for complex IV (MD = 0.18, LOA = -0.86 to 1.21), between PBMCs and permeabilized muscles fibers. No significant relationships were observed between NIRS mitochondrial capacity and respiration in permeabilized muscle fibers. This is the first study to explore and support the agreement of less invasive clinical techniques for assessing mitochondrial respiratory capacity in individuals with SCI. The findings will assist in the application of PBMCs as a viable alternative for assessing mitochondrial health in persons with SCI in future clinical studies.
Highlights
Within most eukaryotic cells, mitochondria serve a pivotal role as a robust Adenosine triphosphate (ATP)-generating system [1, 2]
The findings will assist in the application of Peripheral blood mononuclear cells (PBMC) as a viable alternative for assessing mitochondrial health in persons with spinal cord injury (SCI) in future clinical studies
Mitochondrial dysfunction may contribute to obesity and insulin resistance which can lead to the development of cardiovascular disease and Type 2 diabetes mellitus (T2DM), chronic diseases that are commonplace within the spinal cord injury (SCI) population [4, 5]
Summary
Mitochondria serve a pivotal role as a robust ATP-generating system [1, 2]. A previous study demonstrated that during an acute bout of electrical stimulation, persons with SCI heavily rely on carbohydrate utilization compared to fat utilization as demonstrated by the respiratory exchange ratio, which may indirectly suggest diminished mitochondrial activity [10] It is still unclear whether mitochondrial dysfunction contributes to this observed pattern of substrate utilization after SCI. Multiple studies have shown that electrical stimulation training of muscle may yield increased muscle endurance, function increases in oxidative enzyme activity and gene expression [11–14] These results suggest that improved muscle function may be mediated by mitochondrial capacity and highlights the need for clinical evaluation tools to assist in monitoring skeletal muscle function in this population [15]. An improved understanding of the cellular response of skeletal muscles in chronic SCI may help clinicians better formulate therapeutic and rehabilitative regimens for improving the long-term health and quality of life for persons living with SCI [13, 16]
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