# Hyperbaric Oxygen Therapy in Experimental Autoimmune Myocarditis: Insights from Preclinical Models to Translational Perspectives

**Authors:** Bozidar Pindovic, Vladimir Zivkovic, Radisa Pavlovic, Djurdjina Petrovic, Maja Muric, Ivan Srejovic, Dmitry Kolesov, Marina Kolotilova, Sergey Bolevich, Zarko Finderle, Vladimir Jakovljevic, Aleksandra Stojanovic

PMC · DOI: 10.3390/pathophysiology33010018 · Pathophysiology · 2026-02-14

## TL;DR

Hyperbaric oxygen therapy may help treat autoimmune myocarditis by reducing inflammation and protecting heart cells, but more research is needed to confirm its effectiveness in humans.

## Contribution

This paper explores HBOT as a novel multimodal intervention for autoimmune myocarditis by integrating preclinical findings and translational challenges.

## Key findings

- HBOT suppresses NF-κB and NLRP3 inflammasomes, reducing inflammation in autoimmune myocarditis models.
- HBOT improves oxygen delivery to inflamed heart tissue and protects mitochondrial function.
- Translational barriers include inconsistent protocols and lack of long-term outcome data in human trials.

## Abstract

Myocarditis is still a major global health issue that frequently manifests due to oxidative stress, immune-mediated myocardial damage, and unpredictable clinical progression. Experiments with autoimmune myocarditis (EAM) models have shown different ways that T-cell subsets, proinflammatory cytokines, macrophage polarization, and mitochondrial dysfunction are all connected and play a part in both acute inflammation and chronic remodeling of the heart. As a possible multimodal intervention that could affect several of these disease-causing pathways, hyperbaric oxygen therapy (HBOT) has become popular. This therapy delivers 100% oxygen to different tissues at higher atmospheric pressures. Early research shows that HBOT improves the delivery of oxygen to the inflamed myocardium, suppress the activation of NF-κB and NLRP3 inflammasomes, lowers oxidative stress, protects mitochondrial function, and boosts immune-regulatory T-cell responses. Despite these potentially promising findings, there are still a number of important translational obstacles to overcome, such as inconsistent protocols, a lack of long-term outcome data, insufficient mechanistic profiling, and doubts about the best protocol length and patient selection. To assess safety and effectiveness in human myocarditis, future studies should aim to integrate multi-omics analyses, HBOT regimens that are already standardized, sophisticated imaging, and carefully planned early-phase clinical trials. Overall, the currently available evidence supports HBOT as a biologically plausible and potentially valuable adjunct therapy for autoimmune myocarditis, expressing the need for further mechanistic and clinical investigation.

## Linked entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548]
- **Diseases:** myocarditis (MONDO:0004496), autoimmune myocarditis (MONDO:0022519)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Lgals3 (galectin 3) [NCBI Gene 83781] {aka AGE-R3, CBP30, L-34, gal-3}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, SMAD4 (SMAD family member 4) [NCBI Gene 4089] {aka DPC4, JIP, MADH4, MYHRS}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Lgals3 (lectin, galactose binding, soluble 3) [NCBI Gene 16854] {aka GBP, L-34, Mac-2, gal3}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CAT (catalase) [NCBI Gene 847], NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, ATN1 (atrophin 1) [NCBI Gene 1822] {aka B37, CHEDDA, D12S755E, DRPLA, HRS, NOD}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}
- **Diseases:** cardiac arrest (MESH:D006323), cancer (MESH:D009369), endothelial dysfunction (MESH:D014652), lung diseases (MESH:D008171), diabetic (MESH:D003920), pain (MESH:D010146), hyperoxia (MESH:D018496), myocardial remodeling (MESH:D064752), mitochondrial damage (MESH:D028361), Inflammation (MESH:D007249), heart injury (MESH:D006335), cardiomyocyte injury (MESH:D014947), Disease (MESH:D004194), fibrosis (MESH:D005355), HBOT (MESH:D000860), seizures (MESH:D012640), Gal-3 deficiency (MESH:C537153), metabolic dysregulation (MESH:D021081), myocardial damage (MESH:D009202), refractory angina (MESH:D000069279), fatigue (MESH:D005221), sudden cardiac deaths (MESH:D016757), Autoimmune Myocarditis (MESH:D009205), carbon monoxide poisoning (MESH:D002249), hypoxic (MESH:D002534), arrhythmias (MESH:D001145), autoimmune disease (MESH:D001327), toxicity (MESH:D064420), bone infections (MESH:D001847), vascular dysfunction (MESH:D002561), cardiovascular (MESH:D002318), dilated cardiomyopathy (MESH:D002311), infection (MESH:D007239), Myocardial infarction (MESH:D009203), pneumothorax (MESH:D011030), COVID-19 (MESH:D000086382), ischemic heart disease (MESH:D017202), cytotoxic T (MESH:D001260), atherosclerosis (MESH:D050197), barotrauma (MESH:D001469), viral infections (MESH:D014777), brain damage (MESH:D001925), diabetic foot ulcers (MESH:D017719), endotoxemia (MESH:D019446), tissue injury (MESH:D017695), post-COVID-19 (MESH:D000094024), Radiation injuries (MESH:D011832), decompression sickness (MESH:D003665), cardiac abnormalities (MESH:D018376), immune dysregulation (OMIM:614878), necrosis (MESH:D009336), cardiac damage (MESH:D006331), coronary artery disease (MESH:D003324), osteomyelitis (MESH:D010019), EAE (MESH:D004681), congestive heart failure (MESH:D006333)
- **Chemicals:** Oxygen (MESH:D010100), nitric oxide (MESH:D009569), myricetin (MESH:C040015), RNS (MESH:D026361), Immune Checkpoint (-), melatonin (MESH:D008550), ROS (MESH:D017382), lipids (MESH:D008055), lipopolysaccharide (MESH:D008070), glutathione (MESH:D005978)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## References

99 references — full list in the complete paper: https://tomesphere.com/paper/PMC12921730/full.md

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Source: https://tomesphere.com/paper/PMC12921730