Hydrogen Gas Insufficiency in Mitigating Intestinal Mucosal Injury in NOMI Without Transmural Necrosis: A Critical Swine Model Assessment

Abstract

We read with great interest the study by Tanaka et al. [1]. Investigated hydrogen inhalation therapy in a swine model of non-occlusive mesenteric ischemia (NOMI). The authors should be commended for establishing a reproducible model combining hemorrhagic shock and vasopressor administration and for being the first to evaluate hydrogen therapy in this setting. Given the poor prognosis of NOMI and the absence of widely effective therapies, this study is timely and valuable.

The reported findings that hydrogen inhalation did not significantly mitigate histological ischemic injury in the absence of transmural necrosis are important, as they suggest that hydrogen therapy alone may not be sufficient for NOMI treatment. However, we wish to highlight two issues that influence clinical interpretation.

First, the model design may not have allowed for the assessment of the potential benefits of hydrogen. The study was terminated at 4 h without the development of transmural necrosis; however, clinical NOMI typically evolves over days with progressive microcirculatory compromise. In this relatively early phase, mucosal changes may be subtle and below the threshold at which antioxidant effects translate into measurable histological benefits. Therefore, the absence of an effect within this time frame may reflect the study design rather than true therapeutic inefficacy. From a clinical standpoint, this distinction matters [2]; clinicians may wrongly conclude that hydrogen therapy has no role at any stage of NOMI when, in fact, its impact may emerge under longer observation or more severe ischemic injury.

Second, the sample size was insufficient to detect modest differences. The power calculation indicated that 64 animals per group were needed, yet only four were studied. While practical constraints are understandable in large-animal research, a small cohort increases the risk of type II error. A nonsignificant result should not be interpreted as the absence of an effect, but rather as inconclusive. Translating this into clinical terms, the current findings should temper enthusiasm for hydrogen inhalation as a standalone therapy but should not dismiss its potential contribution as part of a multimodal approach, for example, combined with early vasodilator infusion or optimized hemodynamic support [3].

Despite these limitations, this study makes a valuable contribution by demonstrating the safety and feasibility of hydrogen inhalation in a critical illness model. This is an essential prerequisite for further translational studies. Importantly, this opens the door for future investigations into whether hydrogen might synergize with other therapies in NOMI, particularly at later disease stages, where oxidative stress is more pronounced.

No funding was received.

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The authors declare that they have no conflicts of interest.