Hyperbaric oxygen alters intracellular bioenergetics distribution in human dermal fibroblasts

Hyperbaric oxygen therapy (HBOT), used to promote wound healing, has limited efficacy in many clinical conditions. Wound healing exerts bioenergetic demands on cells that can exceed their intrinsic bioenergetic capacity to proliferate and migrate. The aim of this investigation was to quantify the effects of HBOT on mitochondrial dynamics and bioenergetics functions in cells relevant to wound healing.

High-resolution respirometry and fluorescence microscopy were used to quantify mitochondrial respiration, intermembrane potential, dynamics, including motility, and the intracellular distribution of mitochondrial bioenergetic capacity partitioned into perinuclear and cell peripheral regions in cultured human dermal fibroblasts. Cells were subjected to a range of gas mixtures and hyperbaric pressures, including conditions utilized in clinical care.

Motility was reduced immediately following all HBOT exposures utilized in experiments. Inhomogeneities in intermembrane potential and respiration parameters were produced by different HBOT conditions. The partitioning of ATP-linked respiration was also HBOT-condition dependent. Application of HBOT at common clinical pressure and oxygen conditions resulted in the largest immediate decrement in mitochondrial motility and reductions in ATP-linked respiration in both the cell periphery and perinuclear zones. Aberrations in motility and respiration were also present 6 h after exposure.

HBOT produces intracellular distinctions and inhomogeneities in mitochondrial dynamics and bioenergetics. HBOT as is commonly applied in clinical medicine induced undesirable and persistent alterations in bioenergy function needed to support cell migration and/or proliferation. There may be alternative HBOT parameters that more effectively engender maintenance and adequacy of intracellular bioenergy supply to promote wound healing.