Application and progress of hyperbaric oxygen therapy in cardiovascular diseases

Abstract

Cardiovascular diseases remain the leading cause of death worldwide, underscoring the urgent need for additional therapeutic strategies to reduce their mortality rates. This review systematically outlines the historical development and recent advances of hyperbaric oxygen therapy in cardiovascular diseases, with a focus on its therapeutic mechanisms and clinical outcomes. Hyperbaric oxygen therapy enhances oxygen delivery to ischemic and reperfused tissues, promotes angiogenesis, and significantly suppresses oxidative stress, inflammatory cascades, and cardiomyocyte apoptosis, demonstrating multifaceted therapeutic potential in cardiovascular conditions. Specifically, hyperbaric oxygen therapy combined with reperfusion strategies has been shown to markedly improve left ventricular ejection fraction in acute myocardial infarction. In heart failure, it facilitates myocardial repair and enhances cardiac function. For arrhythmias, hyperbaric oxygen therapy effectively reduces the frequency and duration of premature ventricular contractions and paroxysmal tachycardia, while mitigating the risk of neurological complications following atrial fibrillation ablation. Furthermore, hyperbaric oxygen therapy preconditioning in cardiac surgery has demonstrated improvements in left ventricular stroke work, reductions in postoperative myocardial injury, and a decrease in related complications. Despite its promising applications, the widespread adoption of hyperbaric oxygen therapy remains hindered by the lack of standardized treatment protocols and high-quality evidence from rigorous clinical trials. In conclusion, this review underscores the potential value of hyperbaric oxygen therapy in the cardiovascular domain while highlighting the need for further optimization of therapeutic parameters and exploration of its synergistic effects with conventional therapies to provide clearer guidance for clinical implementation.

Introduction

In 1662, British physician Henshaw pioneered the use of compressed air for hyperbaric oxygen therapy (HBOT).1 Since then, the medical field has explored the therapeutic potential of pressurized air. By the late 19^th century, the therapeutic effects of oxygen and the physical principles governing gas solubility were better understood, driving the application of enhanced oxygen delivery through increased pressure. HBOT involves placing a patient in a hyperbaric chamber to inhale 100% pure oxygen at pressures exceeding normal atmospheric levels. Typically, the oxygen pressure within the chamber ranges from 1.5 to 3 times sea-level atmospheric pressure, leading to alveolar partial pressure of oxygen (pO₂) of several thousand mmHg (e.g., at 2 atmospheres absolute (ATA) or 202.65 kPa, the alveolar pO₂ can exceed 1500 mmHg2). At standard atmospheric pressure (1 atmosphere or 760 mmHg), inhaled oxygen is usually 21% (ambient air) or 100% (pure oxygen), with alveolar pO₂ typically not exceeding 150 mmHg.2 During HBOT, oxygen penetrates more deeply into ischemic or hypoperfused tissues via diffusion, bypassing vascular obstructions and enhancing oxygen delivery to tissues. Patients undergoing HBOT breathe pure oxygen in an enclosed chamber, with oxygen pressure and treatment duration tailored to their specific pathological condition. A single HBOT session may last from a few minutes to 2 hours, with pressure gradually returning to normal levels by the end.3 HBOT has been widely applied clinically for conditions such as carbon monoxide poisoning, decompression sickness, air embolism, and inflammatory bowel disease.4,5,6,7 However, clinical evidence for HBOT in cardiovascular diseases remains limited. Cardiovascular diseases continue to be the leading cause of mortality worldwide, even with improved preventive measures and risk factor control. Nearly half of these deaths are attributed to ischemic heart disease, a major contributor to global morbidity and mortality.8,9 This burden disproportionately affects low- and middle-income countries, causing nearly 7 million deaths and 129 million disability-adjusted life years annually.10,11,12,13 Beyond risk factor control, reducing myocardial ischemia caused by coronary artery occlusion plays a crucial role in preventing cardiomyocyte death and adverse cardiac remodeling. Limiting cardiomyocyte loss significantly improves patient outcomes. Therapeutic angiogenesis, which enhances neovascularization following myocardial infarction (MI), is critical for improving cardiac function and reducing the risk of heart failure (HF). The pathogenesis of myocardial ischemia-reperfusion (I/R) injury is complex and involves oxidative stress, calcium overload, endothelial dysfunction, inflammation, and apoptosis.14,15,16 HBOT promotes angiogenesis in infarcted myocardium and significantly elevates oxygen concentrations in I/R tissues, increasing oxygenation in hypoxic regions and facilitating ischemic recovery.17,18,19 Furthermore, HBOT exhibits anti-oxidative,20 anti-inflammatory,21 and anti-apoptotic properties.19 These mechanisms underscore the theoretical and clinical significance of HBOT in cardiovascular diseases. By improving patient outcomes, mitigating disease severity, reducing economic burdens, and enhancing quality of life, HBOT offers a novel adjunctive approach to cardiovascular treatment. This review aims to synthesize and critically discuss the current understanding of HBOT mechanisms in the cardiovascular field. Our objective is to provide a comprehensive literature overview, summarizing key findings and exploring how these mechanisms influence the progression of cardiovascular diseases.

Methods

We conducted a comprehensive search of studies on HBOT published in English between January 1, 1990, and August 1, 2024, in PubMed and Web of Science databases. On PubMed, we applied the following search strategy: ((“Hyperbaric Oxygenation”[MeSH] OR “Hyperbaric Oxygen Therapy” OR “HBOT” OR “Hyperoxia” OR “Hyperbaric Oxygen”) AND (“Cardiovascular Diseases”[MeSH] OR “Myocardial Infarction”[MeSH] OR “Heart Failure”[MeSH] OR “Arrhythmias, Cardiac”[MeSH] OR “Coronary Artery Disease”[MeSH] OR “Ischemia”[MeSH] OR “Angina, Unstable”[MeSH] OR “Atherosclerosis”[MeSH])) AND (“1990/01/01”[PDat] : “2024/08/01”[PDat]). This search yielded 3025 preliminary results. On Web of Science, a similar search identified 2454 preliminary results. We screened the titles and abstracts of these articles, focusing on studies related to HBOT and cardiovascular diseases while excluding irrelevant studies or those with inconclusive findings. Additionally, we manually reviewed the references of selected articles and included papers that, based on consensus among the authors, provided significant insights into specific mechanisms or areas of interest. This process adhered to the following criteria. The inclusion criteria were as follows: (1) Study population: limited to patients with cardiovascular diseases, including acute coronary syndromes, MI, arrhythmias, and chronic heart failure; (2) Interventions: studies must include HBOT as an intervention; (3) Outcome measures: study outcomes must report key cardiovascular therapeutic indicators such as survival rates, cardiac function recovery, and quality of life improvements; (4) Animal models: studies using animal models that provide in-depth exploration of HBOT mechanisms in cardiovascular therapy or supplemental mechanistic insights. The exclusion criteria were: (1) Studies not focused on cardiovascular diseases; (2) Studies that did not use HBOT as an intervention; (3) Studies with severe design flaws; (4) Studies with incomplete data or unclear outcome reporting; (5) Duplicate publications; and (6) Non-English publications. Ultimately, 78 studies were included in this review, comprising 3 guidelines, 4 books, 11 randomized controlled trials (RCTs), 13 observational studies, 17 reviews, 6 case reports, and 24 basic science studies.

Physiology of Hyperbaric Oxygen Therapy

Arterial oxygen content

Oxygen is a critical element for cellular metabolism and energy production. However, pathological conditions can impair the body’s ability to deliver oxygen to tissues, increase tissue oxygen demand, and extend the distance that oxygen must travel from capillaries to cells. Although the average intracellular pO₂ is approximately 23 mmHg—sufficient to meet cellular oxygen requirements—conventional oxygen therapy may struggle to ensure adequate cellular oxygenation in ischemic or post-ischemic tissues. Cells require intracellular PO₂ levels of 1–3 mmHg to fully support metabolic processes.2 Perfusion, along with the variable degrees of vasodilation and vasoconstriction within different tissues, can severely compromise blood flow in such conditions. By increasing arterial pO₂, more oxygen can be delivered to deeper tissues. Elevating ambient pressure from 1 atmosphere absolute (ATA) to 2–2.5 ATA while inhaling 100% oxygen under pressure can increase plasma oxygen concentration nearly 17-fold. Theoretically, under 100% oxygen at 2.5 ATA, sufficient oxygen can dissolve in plasma to meet the body’s resting metabolic demands without requiring hemoglobin.1 This level of pressure is characteristic of HBOT. By increasing the PO₂, HBOT enhances the dissolved oxygen content in blood, significantly increasing oxygen delivery even when hemoglobin is fully saturated. This hyperoxic environment supports improved oxygenation of ischemic myocardium, particularly in cases of MI or ischemia.22 As such, HBOT may enhance left ventricular ejection fraction (LVEF), alleviate symptoms in HF patients, and improve myocardial oxygenation and microcirculatory perfusion. By increasing the efficiency of myocardial metabolism, HBOT can reduce myocardial oxygen consumption.18,19

Hemodynamics

Several hemodynamic changes are known to occur during and after exposure to HBOT.23 The primary effect is vasoconstriction induced by HBOT at pressures of 1.9–3 ATA. This response is a physiological protective mechanism against the extremely high arterial PO₂, safeguarding tissues from increased oxidative damage.23 Additionally, this vasoconstriction raises systemic vascular resistance, thereby increasing cardiovascular afterload. These changes are associated with an elevation in systolic blood pressure and mean arterial pressure. Cardiac output decreases primarily due to a reduction in heart rate.24 When HBOT is applied at pressures below 1.5 ATA, it exerts several beneficial effects on the heart. Mild HBOT enhances contractile velocity before ischemia, improves end-diastolic pressure during ischemia, and optimizes pressure development during reperfusion, reducing wasted energy during cardiac workload. This enhances the efficiency of myocardial contraction and reduces the infarct size. On the arterial side, mild HBOT improves vasodilation by enhancing vascular sensitivity to acetylcholine and increasing plasma nitrite levels, thereby improving blood supply to ischemic regions.25

Biological Mechanisms of Hyperbaric Oxygen Therapy

Anti-inflammatory effects

Acute cardiac inflammation is characterized by the continuous release of inflammatory mediators, leading to the immediate influx of polymorphonuclear leukocytes, followed by phagocytosis, monocyte and macrophage activity, proteolysis, angiogenesis, and collagen deposition. In the early stages of acute MI (AMI), HBOT exhibits both bacteriostatic and bactericidal effects while modulating inflammatory mediators.21 It reduces pro-inflammatory cytokines, increases anti-inflammatory cytokines, and induces hypoxia-inducible factor and vascular endothelial growth factor through a complex molecular and cellular cascade involving β2 integrins.26,27,28 Evidence suggests that HBOT enhances the activity of inducible nitric oxide synthase-2 and myeloperoxidase, resulting in S-nitrosylation of β-actin within neutrophils. This S-nitrosylation inhibits the aggregation of β2 integrins, reducing neutrophil adhesion to endothelial cells. This reduction in adhesion significantly mitigates tissue injury caused by neutrophil activation during I/R.29 Moreover, HBOT does not impair neutrophil survival or their critical defensive functions, such as degranulation, phagocytosis, and oxidative burst.29 Thus, HBOT suppresses excessive neutrophil adhesion in specific inflammatory responses while preserving their functional integrity, thereby reducing oxidative stress-induced cellular damage (Figure 1A–D).

Figure 1.

Mechanism of HBOT in the cardiovascular system.

(A) HBOT mitigates tissue damage caused by neutrophil activation by reducing β2-integrin aggregation. (B) HBOT promotes angiogenesis by upregulating MALAT1 in cardiac microvascular endothelial cells, which in turn inhibits miR-92a. (C) In cardiomyocytes, hypoxia suppresses the expression of ARE-related genes within 1–7 days. HBOT reverses this suppression by activating the Mst1/Keap1/Nrf2/HO-1 axis. After > 28 days of hypoxia, myocardial damage worsens, and HBOT alleviates this by regulating downstream factors of Mst1 to inhibit cardiomyocyte apoptosis. (D) In macrophages, the expression of Mst1 under hypoxic conditions shows an inverse pattern compared to cardiomyocytes during the initial 1–7 days, likely reflecting normal pathological processes. HBOT repairs myocardial damage by downregulating pro-inflammatory gene expression and upregulating anti-inflammatory gene expression through inhibition of the MST1-5-LOX-LTB4-BLT1 axis. Created with WPS Office, version 12.1.0.19302. 5-LOX: 5-Lipoxygenase; ARE: antioxidant response element; ERK: extracellular signal-regulated kinase; FLAP: 5-lipoxygenase-activating protein; HBOT: hyperbaric oxygen therapy; HO-1: heme oxygenase-1; JNK: c-Jun N-terminal kinase; Keap1: Kelch-like ECH-associated protein 1; LTB4: leukotriene B4; MALAT1: metastasis-associated lung adenocarcinoma transcript 1; MST1: mammalian Sterile 20-like kinase 1; NF-KB: nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf2: nuclear factor erythroid 2-related factor 2; ROS: reactive oxygen species.

Anti-oxidant effects

In the early stages of AMI (1–7 days), HBOT protects the heart from I/R injury by mitigating oxidative stress-induced damage.20 Previous studies have demonstrated that activating the mammalian sterile 20-like kinase 1 (Mst1)/Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 axis and inhibiting reactive oxygen species production can protect the heart from I/R injury.30,31 Mst1, a serine-threonine kinase, has been shown to regulate acute cardiac I/R injury.20 Nrf2, a critical oxidative stress sensor and transcription factor, plays a protective role in cellular antioxidant defense.32 Under normal conditions, Nrf2 is bound to its inhibitory factor, Keap1. However, during HBOT, Nrf2 is released from Keap1, translocates to the nucleus, and accumulates. Once in the nucleus, Nrf2 binds to antioxidant response element-associated genes, initiating their expression to reduce oxidative damage and maintain cellular redox homeostasis.31 By activating these genes, the Nrf2-regulated signaling pathway promotes the expression of genes encoding antioxidant, anti-inflammatory, and cytoprotective proteins, effectively reducing oxidative stress-induced cellular injury33,34 (Figure 1C).

Anti-apoptotic effects

Loss of cardiomyocyte function is a critical cause of mortality in cardiovascular diseases, with MST1 acting as a key pro-apoptotic factor in cardiomyocytes. MST1 has been shown to regulate chronic cardiac metabolic injury.35,36 In the later stages of MI (e.g., after 28 days), MST1 expression typically increases, which is associated with impaired cardiac function and the development of fibrosis.36 This upregulation of MST1 may be linked to the absorption of endothelial cell-derived exosomes by cardiomyocytes, leading to elevated MST1 protein levels.37 Endothelial cell-derived exosomes are also known to influence macrophage function.38 The regulation of MST1 appears to be time-dependent. Liu et al.39 reported the expression of endogenous MST1 in cardiac macrophages from wild-type mice at 1, 3, and 7 days post-MI. Compared to day 0, MST1 expression decreased during the first 3 days after MI, reaching its lowest level on day 1, followed by a moderate increase by day 7. Although MST1 upregulation can exacerbate cardiomyocyte apoptosis through multiple mechanisms,35,40,41,42 HBOT may avoid uncontrolled inflammation associated with MST1 inhibition.39 This is likely because HBOT reduces cardiomyocyte apoptosis by modulating downstream effectors of MST119 (Figure 1D).

Pro-angiogenic effects

HBOT has been shown to promote capillary regeneration.43 A study indicates that at 2.5 ATA, HBOT significantly increases the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in human coronary artery endothelial cells and their derived exosomes.43 Endothelial cell-derived MALAT1 plays a regulatory role in vascular growth and function,44 and its HBOT-induced expression exhibits time- and load-dependent characteristics. MALAT1 is a pro-angiogenic long non-coding RNA with complementary sequences to miR-92a.45 Previous research has shown that miR-92a plays a critical role in angiogenesis: its overexpression in endothelial cells blocks angiogenesis, whereas its inhibition enhances it.46,47 Furthermore, inhibiting miR-92a in animal models prevents I/R injury and endothelial dysfunction.48,49 HBOT significantly reduces miR-92a expression in human coronary artery endothelial cell-derived exosomes, and suppressing MALAT1 expression reverses these miR-92a changes.43 Thus, HBOT promotes angiogenesis by upregulating MALAT1, which in turn suppresses miR-92a expression (Figure 1B).

Applications of Hyperbaric Oxygen Therapy in the Cardiovascular System

Acute myocardial infarction

The role of HBOT in the treatment of AMI remains controversial. In a multi-center RCT investigating the use of HBOT following thrombolysis in AMI patients,50 participants in the HBOT group were transferred to a hyperbaric chamber immediately after thrombolysis. The treatment protocol involved compression to 2 ATA within 30 minutes, maintenance of hyperbaric conditions for 1 hour, and decompression over 30 minutes, with a total session duration of approximately 2 hours. The mean time from initiation of thrombolysis to the start of HBOT was 71 minutes. Results demonstrated that combining HBOT with thrombolysis was feasible and safe for AMI patients, potentially leading to attenuated creatine phosphokinase elevation, faster pain resolution, and improved ejection fraction. Another RCT involving 74 AMI patients initiated HBOT an average of 10 hours after thrombolysis.51 Patients were compressed to 2 ATA over 20 minutes, maintained at this pressure for 1 hour, and then decompressed over 20 minutes. After 3 weeks, the HBOT group showed a significant improvement in ejection fraction compared to the control group (increase from 46.27% to 50.81% vs. decrease from 45.54% to 44.05%, P < 0.05). A further RCT assessed HBOT in patients with ST-elevation MI following percutaneous coronary intervention.52 HBOT was initiated 3 days after the primary percutaneous coronary intervention, delivered daily at 2 ATA for 90 minutes per session over 15 sessions. At 6 weeks, single-photon emission computed tomography imaging revealed that the HBOT group had a greater reduction in the number of affected segments, compared to the control group. These findings suggest that HBOT can improve cardiac function in AMI patients. In animal studies, HBOT has been shown to significantly reduce oxidative stress, inflammation, and apoptosis following MI14,19,20,34,53,54 (Table 1). However, in clinical studies, Kim et al.55 reviewed 2376 patients with myocardial injury and stratified them into three groups based on arterial pO₂: normoxia (60–120 mmHg), mild hyperoxia (120–180 mmHg), and severe hyperoxia (> 180 mmHg). Although the mode of oxygen delivery was unclear, their results indicated that higher oxygen levels within 24 hours of admission were associated with increased 28-day in-hospital mortality in patients with myocardial injury. Overall, these data support the early application of HBOT after thrombolysis or percutaneous coronary intervention in AMI patients. This benefit may primarily stem from the early reduction of inflammatory responses. Other mechanisms likely include enhanced oxygenation of I/R tissues, promotion of angiogenesis, and inhibition of apoptosis.

Table 1.

Efficacy of hyperbaric oxygen therapy in myocardial infarction animal models

Study	Animal	Parameter of hyperbaric oxygen	Efficacy
Liu et al.30	Wistar rats	2.0 ATA 60 min Once daily for 4 consecutive days	Reduce in myocardial infarction size; Increase in left ventricular systolic pressure and decrease in left ventricular diastolic pressure; Inhibit oxidative stress and inflammatory response
Oliveira et al.54	Wistar rats	2.0 ATA 60 min Single session administered immediately following coronary artery occlusion	Reduce mortality rate; Enhance anti-oxidant capacity; Alleviate oxidative stress
Chen et al.53	Sprague-Dawley rats	60 min Once daily for 14 consecutive days	Reduce myocardial injury; Decrease inflammatory cytokines
Chen et al.20	Sprague-Dawley rats	2.5 ATA 60 min Once daily for 14 consecutive days	Increase left ventricular systolic pressure, reduce left ventricular end-diastolic pressure and heart rate; Reduce infarct size; Decrease the levels of oxidative stress; Inhibit myocardial apoptosis; Improve endothelial function
Yin et al.34	Wild-type and Nrf/- mice (C57B/SV129)	2.0 ATA 60 min Once daily for 14 consecutive days	Reduce myocardial infarction size; Attenuate oxidative stress response; Decrease the levels of inflammatory markers
Sun et al.19	Sprague-Dawley rats	3.0 ATA 20 min Four consecutive sessions, with 20-min interval	Reduce myocardial infarct size; Increase left ventricular systolic pressure and decrease left ventricular end-diastolic pressure; Reduce apoptosis

Heart failure

AMI is a major contributor to the development of HF. HBOT has been shown to induce the production of heat shock proteins, which confer protective effects.56 By enhancing the induction of endogenous heat shock proteins, HBOT may aid in repairing and improving cardiac function impaired by MI. However, the use of HBOT in HF patients remains controversial, with inconsistent recommendations regarding its indications. On one hand, left ventricular systolic dysfunction is considered a relative contraindication for HBOT.57 On the other hand, it has been suggested that HF patients can safely undergo HBOT after optimization of HF treatment and fluid restriction.58 Weaver and Churchill57 reported three cases of pulmonary edema in patients with reduced LVEF who underwent HBOT at 2.0–2.4 ATA for 20–40 minutes. Two of these patients improved after treatment with diuretics and nitroglycerin, while one patient died. Based on these findings, the authors recommended caution when using HBOT in HF patients or those with reduced ejection fraction. More recently, Schiavo et al.59 reviewed 23 HF patients who underwent HBOT, completing an average of 39 sessions (range: 6–62). Treatment pressures were 2.0 ATA (11 patients) or 2.4 ATA (12 patients). Of these, 13 patients had preserved ejection fraction (mean LVEF 55 ± 7%), 7 had reduced ejection fraction (mean LVEF 35 ± 8%), and 3 had mid-range ejection fraction (mean LVEF 44 ± 4%). Coexisting conditions included right heart dysfunction (5 patients), moderate-to-severe tricuspid regurgitation (3 patients), and pulmonary hypertension (5 patients). During the study, two cases of pulmonary edema related to HBOT were observed: one in a reduced ejection fraction patient (LVEF 24%) and the other in an preserved ejection fraction patient (LVEF 64%). Both cases resolved with diuretic treatment. Notably, this study was the first to explore the safety of HBOT in patients with varying degrees of LVEF, including those with preserved ejection fraction and reduced ejection fraction. The findings encompass a range of cardiac function states and provide valuable clinical guidance. The development of pulmonary edema during HBOT in HF patients is likely attributable to a physiological protective response to extremely high arterial pO₂.23 HBOT induces peripheral vasoconstriction, which increases venous return (preload) and arterial resistance (afterload). For HF patients, particularly those with impaired cardiac pump function, this additional burden may elevate pulmonary venous pressures, increase capillary permeability, and result in pulmonary edema.

Arrhythmias

HBOT is associated with a significant increase in parasympathetic tone.24 During HBOT, reductions in the frequency and duration of premature ventricular contractions and paroxysmal ventricular tachycardia in MI patients have been observed.59 A RCT reported that patients received HBOT treatments of 90 minutes per session, five times a week for 8 consecutive weeks (40 sessions in total) at a pressure of 2.5 ATA.60 Only patients who completed more than 35 sessions were included in the final analysis. After 5 years of follow-up, the HBOT group demonstrated a significantly shorter QTc interval compared to the placebo group (438 ms vs. 453 ms, P < 0.05). Observational studies have also noted that HBOT can reduce QTc intervals.61,62 Given that prolonged QT intervals and increased QT dispersion are associated with heterogeneity in ventricular repolarization, which may progress to malignant arrhythmias—particularly in MI patients—HBOT appears to reduce this risk.63,64,65 Similarly, atrial fibrillation (AF), the most common arrhythmia in the elderly, is associated with severe complications such as thrombosis, stroke, and HF.66 In patients undergoing radiofrequency ablation for AF, initiating HBOT within 4 hours of air embolism occurrence, at pressures of 2.4–3 ATA for 120 minutes per session, has been shown to reduce neurological sequelae associated with cerebral air embolism.67,68 Furthermore, studies have found that HBOT at 2.5 ATA for 120 minutes per session is effective in treating AF induced by carbon monoxide poisoning.69,70 While these findings suggest potential benefits, AF patients often present with comorbidities such as diabetes.66 Further research is needed to determine whether early HBOT can mitigate the incidence of AF in these patients.

Coronary artery bypass grafting

Emerging evidence suggests that HBOT offers benefits as an adjunctive therapy for patients undergoing coronary artery bypass grafting (CABG). In a RCT, preconditioning with HBOT at 2.4 ATA was performed approximately 4 hours before the first elective on-pump CABG surgery in patients with coronary artery disease.71 The protocol involved compression to 2.4 ATA within 10 minutes, maintaining this pressure for 30 minutes, followed by a 5-minute interval, another 30 minutes at 2.4 ATA, and decompression over 25 minutes, totaling approximately 105 minutes. Results demonstrated that HBOT preconditioning before on-pump CABG significantly improved LVSW, and reduced myocardial injury post-CABG, intraoperative blood loss, ICU stay duration, postoperative complications, and overall costs. Similarly, another RCT evaluated the protective effects of HBOT preconditioning on the brain and myocardium in patients undergoing both on-pump and off-pump CABG.72 Patients received daily HBOT for 5 consecutive days prior to surgery. The sessions involved compression to 2.0 ATA within 20 minutes, maintaining high pressure for 35 minutes, followed by a 5-minute interval, another 35 minutes at 2.0 ATA, and decompression over 25 minutes, with a total duration of approximately 70 minutes. Results indicated significant neuroprotective and cardioprotective effects in on-pump CABG patients, though no protective effects were observed in off-pump CABG. Current evidence highlights the potential efficacy of HBOT in cardiac surgery settings67,71,72,73,74,75,76,77 (Table 2). Although the quality of these studies needs improvement, they collectively support the appropriateness of HBOT in cardiac surgery patients. However, further research is needed to assess the clinical and cost-effectiveness of HBOT in the rehabilitation and recovery of cardiac surgery patients.

Table 2.

Clinical efficacy of hyperbaric oxygen therapy in cardiac surgery

Study	Type of study	Disease type	Patient information	Parameter of hyperbaric oxygen	Efficacy
Lee et al.76	Retrospective study	Spinal cord ischemia following complex aortic repair	30 patients, 22 males, 65.60 ± 12.17 yr	2.4 ATA 120 min An average of 5.23 sessions	Improve the overall muscle function
Ulus et al.67	Case report	Air embolism to the brain during atrial fibrillation ablation	1 female patient, 51 yr	2.4 ATA 120 min 4 sessions	CT scans revealed the complete resolution of air embolism in the brain
Niyibizi et al.74	Case report	Iatrogenic cerebral air embolism following ventricular septal defect repair and aortic valve reconstruction	1 male patient, 35 yr	2.5—4.0 ATA The first treatment lasted 20 min, the second lasted 170 min, the third lasted 150 min, and subsequent treatments each lasted 95 min Start at 54 h after surgery, consisting of 7 sessions	Complete restoration of neurological function
Li et al.72	Prospective randomized single-blind controlled study	Coronary heart disease	49 male patients, 62.1 ± 2.6 yr	1.0—2.0 ATA 70 min Once daily for 5 consecutive days	Reduce the levels of S100B protein, neuron- specific enolase, and cardiac troponin I in serum
Yogaratnam et al.71	Prospective randomized controlled study	Coronary heart disease	HBOT group: 41 patients, 33 males, 64.7 yr; Control group: 40 patients, 29 males, 68.8 yr	2.4 ATA 30 min Two preoperative sessions (5 min interval)	Improve left ventricular function, accompanied by a notable reduction in pulmonary vascular resistance and systemic vascular resistance; Decrease the duration of intensive care unit hospitalization, intraoperative blood loss, and the incidence of postoperative complications
Mofrad et al.77	Case report	Cerebral air embolism during atrial fibrillation catheter ablation	1 male patient, 44 yr	2–3 ATA The first session lasted 240 min, followed by subsequent sessions of 90 min 4 sessions	Eliminate the cerebral air embolism
Ziser et al.75	Retrospective study	Massive arterial air embolism occurring during cardiac surgery	17 patients, 10 males, 55 ± 26 yr	2.8 ATA 14 patients (82.4%) received a single session	Complete neurological recovery: 8 patients (47.1%); Severe neurological impairment: 6 patients (35.3%); Mortality: 3 patients (17.6%)
Armon et al.73	Case report	Cerebral embolism occurring during mitral valve replacement surgery	1 female patient, 50 yr	Once began 30 h after the air embolism occurred and lasted for 38 h	improve the neurological function

Contradictions of Hyperbaric Oxygen Therapy

Despite progress in the use of HBOT for cardiovascular therapy, several contradictions and uncertainties remain. First, the optimal timing, pressure range, and number of HBOT sessions for AMI and cardiac surgery patients require further evidence-based validation.50,52,71,72 It remains unclear whether HBOT is effective for conditions such as non-ST-elevation MI, angina, and myocardial bridging, or in improving patients’ quality of life, psychological well-being, and long-term prognosis. Second, HF, as a severe manifestation or advanced stage of cardiovascular disease, poses a significant threat to human life. It is associated with poor survival rates of 75.9%, 45.5%, and 24.5% at 1, 5, and 10 years, respectively.78 Although HBOT has demonstrated safety and efficacy across different types of HF,58 future high-quality studies are needed to explore the cumulative effects of HBOT and differential responses among HF subgroups to better guide clinical practice. Lastly, research on HBOT for arrhythmias and cardiac rehabilitation remains limited,59 particularly in patients with concomitant MI. High-quality, multicenter collaborative studies are needed to provide evidence to improve the prognosis and cost-effectiveness of care for these patients. In summary, while HBOT has promising applications in the cardiovascular system, understanding its indications and contraindications is critical. Based on current evidence, indications for HBOT include acute coronary syndromes, MI, HF, premature ventricular contractions, and paroxysmal ventricular tachycardia. Relative contraindications include sick sinus syndrome, second-degree or higher atrioventricular block, bradycardia (< 50 beats/min), and uncontrolled hypertension (> 160/100 mmHg) (Figure 2). Overall, the existing evidence on HBOT’s indications and contraindications in the cardiovascular field is incomplete, underscoring the need for further high-quality research.

Figure 2.

Indications and contraindications of HBOT in cardiovascular medicine.

Current evidence supports the use of HBOT in the management of acute coronary syndromes, myocardial infarction, heart failure, ventricular premature contractions, and paroxysmal tachycardia. However, HBOT is not recommended for conditions such as sick sinus syndrome, second-degree or higher atrioventricular block, bradycardia (< 50 BPM), or severe hypertension (> 160/100 mmHg). BPM: Beats per minute; HBOT: hyperbaric oxygen therapy.

Limitations

This review summarizes the mechanisms, applications, and limitations of HBOT in cardiovascular diseases; however, several limitations should be acknowledged. First, this review includes studies from major databases (e.g., PubMed, Web of Science), which may have excluded relevant research published in other journals or languages. Second, there is considerable variability in the quality and methodologies of the cited studies. A formal assessment of study quality was not conducted, which may contribute to heterogeneity in some conclusions. Third, while this review focuses on the electrophysiological and biological mechanisms of HBOT in the cardiovascular field, the depth of discussion remains limited. Although we provide treatment parameters for key studies on HBOT in cardiovascular medicine, future research should prioritize multi-center RCTs to investigate the specific roles and potential adverse effects of HBOT in different populations and disease stages. Despite these limitations, this review offers a systematic synthesis of current research, providing an important theoretical basis for the application of HBOT in cardiovascular medicine.

Conclusion

This review highlights the role of HBOT in cardiovascular medicine. Recent studies suggest that the therapeutic potential of HBOT in various cardiovascular diseases may be attributed to its ability to enhance tissue oxygenation, promote capillary regeneration, improve microcirculatory perfusion, and optimize energy metabolism. Additionally, HBOT exerts protective effects through mechanisms such as reducing oxidative stress, modulating inflammatory pathways, and regulating apoptosis and cell proliferation. In AMI, combining HBOT with reperfusion strategies improves LVEF. For HF, HBOT may aid in repairing and restoring cardiac function damaged by MI. In the context of arrhythmias, HBOT reduces the frequency and duration of premature ventricular contractions and paroxysmal ventricular tachycardia. Early application of HBOT also shows potential in reducing neurological complications following AF ablation. In cardiac surgery, HBOT preconditioning has been demonstrated to improve LVSW, reduce postoperative myocardial injury and complications, and lower healthcare costs. These findings underscore the promising role of HBOT as a complementary therapeutic approach in cardiovascular medicine, warranting further exploration and validation in clinical practice.

Future Perspectives

Although existing data suggest a promising future for HBOT in cardiovascular diseases, its widespread adoption in clinical practice remains constrained by the lack of standardized treatment protocols and robust clinical evidence. Future research should focus on identifying the optimal timing for HBOT intervention, refining treatment regimens, and investigating its synergistic effects when combined with conventional therapies. Addressing these gaps is essential to fully harness the therapeutic potential of HBOT in cardiovascular medicine while ensuring patient safety and treatment efficacy. In summary, HBOT demonstrates multifaceted benefits in the management of cardiovascular diseases. However, uncertainties surrounding its safety and efficacy currently limit its clinical application. There is an urgent need for well-designed, large-scale trials to validate the therapeutic effects of HBOT and to clarify its role in cardiovascular care.

Data availability statement:

Not applicable.