Restoration of tidal volume after spinal cord injury by hyperbaric oxygen therapy requires both pressure and 100% oxygen

Abstract

Approximately 13,000 spinal cord injuries (SCI) occur each year in the U.S. The majority of SCIs are vertebral crush/contusion injuries at the cervical level. Cervical SCIs often result in impaired ventilation and in severe cases require full time mechanical ventilation. Hyperbaric oxygen (HBO) therapy is a promising non‐invasive treatment for SCI. By exposing the injured spinal cord to higher pressures, 2‐3 atmospheres (ATA), at increased oxygen (100%), HBO therapy helps deliver oxygen to poorly perfused tissues, has anti‐oxidant and anti‐inflammatory impact, and has been reported to mitigate neuronal loss. Additionally, HBO may mitigate muscle atrophy after SCI. Despite the promise of HBO therapy, to our knowledge there have been no studies that have comprehensively controlled for the different variables that are manipulated during HBO treatment (e.g. oxygen level, chamber pressure). In this study, we tested two hypotheses: 1) the benefit of HBO therapy after SCI requires pressurized 100% oxygen vs. either variable alone, and 2) HBO therapy can improve respiratory recovery after cervical SCI. Six experimental groups were included: one without injury (Sham injury), and five groups with a hemicontusion injury at spinal segment C4. The first injured group did not receive any treatment (SCI only), the next group was treated with 2ATA pressure, but 10.5% oxygen to target normal inspired partial pressure of oxygen. The final three groups tested the effect of 100% oxygen at 1, 2, or 3ATA. All treatments were initiated within 2 hours of injury, lasted 1‐hour, and were repeated daily for 10 consecutive days. We measured ventilation using whole body plethysmography prior to injury and on days 5 and 10 post‐injury. During normoxic conditions on day 5, all experimental groups had reduced tidal volume compared to Sham animals. By day 10, however, the tidal volume of animals in the 2ATA and 3ATA group returned to the level of the Sham animals. Further, during a period of respiratory challenge achieved by inspiring a mixed hypercapnic (7% CO2), hypoxic (10.5% O2) gas, only the animals in the 3ATA group matched the tidal volume of the Sham animals. Additionally, cross sectional analysis of the mid‐costal diaphragm revealed a preservation of the size of type IIb/x fibers in the animals in the 3ATA group. This study demonstrates that both pressure (≥2 ATA) and elevated oxygen (100%) are required to improve ventilation, and that higher pressure (3ATA) may confer greater benefits over 2ATA treatment.