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Commentary: A new reason to breathe easy about spinal cord ischemia?

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      Danisa K. Daubenspeck, DO, and Mark A. Chaney, MD
      Many techniques exist for preventing spinal cord ischemia–reperfusion injury; however, no one is universally sufficient. Hydrogen gas has emerged as a new potentially clinically useful strategy.
      See Article page e269.
      Hydrogen gas has emerged as a therapeutic tool for various entities involving ischemia–reperfusion injury (IRI). Animal studies have shown that inhaled hydrogen gas protects against spinal cord IRI. Kimura and colleagues
      • Kimura A.
      • Suehiro K.
      • Mukai A.
      • Fujimoto Y.
      • Funao T.
      • Yamada T.
      • et al.
      Protective effects of hydrogen gas against spinal cord ischemia-reperfusion injury.
      take another step forward, revealing a potential mechanism for these beneficial effects.
      In their comprehensive, well-designed, prospective, randomized rat study, they reveal that inhalation of varying levels of hydrogen gas (1%, 2%, or 3%) before standard induction of spinal cord IRI exerts concentration-dependent protective effects on motor function, seen via histopathologic examination. Furthermore, inhaled hydrogen gas also attenuated spinal cord IRI-induced increases in ventral horn glutamate levels in a concentration-dependent manner. Lastly, the protective effects of inhaled hydrogen gas were not observed in animals receiving a glutamate transporter-1 inhibitor and ventral horn glutamate levels increased in these animals as well. Their results confirm findings of other investigators demonstrating spinal cord IRI-protective effects of inhaled hydrogen gas. Their results also indicate that glutamate transporter-1 may play an important role in this process.
      Despite advances in surgical techniques, spinal cord IRI remains a significant problem after both open repair and endovascular thoracoabdominal aneurysm repair, with incidence reported from 10% to 30%.
      • Awad H.
      • Ramadan M.E.
      • El Sayed H.F.
      • Tolpin D.A.
      • Tili E.
      • Collard C.D.
      Spinal cord injury after thoracic endovascular aortic aneurysm repair.
      • Awad H.
      • Tili E.
      • Nuovo G.
      • Kelani H.
      • Ramadan M.E.
      • Williams J.
      • et al.
      Endovascular repair and open repair surgery of thoraco-abdominal aortic aneurysms cause drastically different types of spinal cord injury.
      • Acher C.
      • Acher C.W.
      • Marks E.
      • Wynn M.
      Intraoperative neuroprotective interventions prevent spinal cord ischemia and injury in thoracic endovascular aortic repair.
      Mechanism of spinal cord IRI is postulated to be caused by alterations in spinal cord perfusion pressure; due to hypotension, increased cerebrospinal fluid (CSF) pressure, or interruption of flow through segmental arteries (SAs) during aortic clamping or during reperfusion after unclamping.
      • Awad H.
      • Ramadan M.E.
      • El Sayed H.F.
      • Tolpin D.A.
      • Tili E.
      • Collard C.D.
      Spinal cord injury after thoracic endovascular aortic aneurysm repair.
      Cause of spinal cord IRI during endovascular thoracoabdominal aneurysm repair is believed to be due to coverage of SAs by graft location, yet a recent pilot study shows magnetic resonance imaging and histologic findings of spinal cord IRI in endovascular thoracoabdominal aneurysm repair may be much different then open repair, suggesting a different mechanism of injury.
      • Awad H.
      • Tili E.
      • Nuovo G.
      • Kelani H.
      • Ramadan M.E.
      • Williams J.
      • et al.
      Endovascular repair and open repair surgery of thoraco-abdominal aortic aneurysms cause drastically different types of spinal cord injury.
      Goals of management strategies address these disparate causes. CSF drainage, among the most studied options, involves perioperative intrathecal catheter placement, with goal of decreasing CSF pressure.
      • Awad H.
      • Ramadan M.E.
      • El Sayed H.F.
      • Tolpin D.A.
      • Tili E.
      • Collard C.D.
      Spinal cord injury after thoracic endovascular aortic aneurysm repair.
      ,
      • Acher C.
      • Acher C.W.
      • Marks E.
      • Wynn M.
      Intraoperative neuroprotective interventions prevent spinal cord ischemia and injury in thoracic endovascular aortic repair.
      Although effective, it comes with significant risk of complications, including neuraxial bleeding, infection, or spinal headache.
      • Awad H.
      • Ramadan M.E.
      • El Sayed H.F.
      • Tolpin D.A.
      • Tili E.
      • Collard C.D.
      Spinal cord injury after thoracic endovascular aortic aneurysm repair.
      Alternatively, maintenance of high mean arterial pressure (>80 mm Hg) may also increase spinal cord perfusion pressure, with improved outcomes when employed with CSF drainage.
      • Awad H.
      • Ramadan M.E.
      • El Sayed H.F.
      • Tolpin D.A.
      • Tili E.
      • Collard C.D.
      Spinal cord injury after thoracic endovascular aortic aneurysm repair.
      Another technique is hypothermia, via passive cooling, localized via epidural saline infusion, or deep hypothermic circulatory arrest.
      • Acher C.
      • Acher C.W.
      • Marks E.
      • Wynn M.
      Intraoperative neuroprotective interventions prevent spinal cord ischemia and injury in thoracic endovascular aortic repair.
      Other options include selective reimplantation of SAs or distal aortic perfusion via an atriofemoral bypass circuit. Pharmacologic interventions such as corticosteroids or barbiturates act to decrease metabolic rate of the spinal cord or function as free radical scavengers to minimize reperfusion injury.
      • Awad H.
      • Ramadan M.E.
      • El Sayed H.F.
      • Tolpin D.A.
      • Tili E.
      • Collard C.D.
      Spinal cord injury after thoracic endovascular aortic aneurysm repair.
      Despite the vast number of various strategies available, no single tactic has proven sufficient to completely abolish spinal cord IRI. Hydrogen gas may be effective in reducing oxidative stress after cardiac arrest, and is now potentially effective against spinal cord IRI.
      • Kimura A.
      • Suehiro K.
      • Mukai A.
      • Fujimoto Y.
      • Funao T.
      • Yamada T.
      • et al.
      Protective effects of hydrogen gas against spinal cord ischemia-reperfusion injury.
      The ability to potentially have a universal, safe, and easily applied technique to avoid the devastating results of spinal cord IRI is a very exciting prospect, and the results of this study conducted by Kimura and colleagues
      • Kimura A.
      • Suehiro K.
      • Mukai A.
      • Fujimoto Y.
      • Funao T.
      • Yamada T.
      • et al.
      Protective effects of hydrogen gas against spinal cord ischemia-reperfusion injury.
      indicate the possible clinical usefulness of hydrogen gas and also open up new avenues for further research.

      References

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        Protective effects of hydrogen gas against spinal cord ischemia-reperfusion injury.
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        • et al.
        Endovascular repair and open repair surgery of thoraco-abdominal aortic aneurysms cause drastically different types of spinal cord injury.
        Sci Rep. 2021; 11: 7834
        • Acher C.
        • Acher C.W.
        • Marks E.
        • Wynn M.
        Intraoperative neuroprotective interventions prevent spinal cord ischemia and injury in thoracic endovascular aortic repair.
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