Hyperbaric Cardiovascular Effects

Function

The U.S. Food and Drug Administration (FDA) has approved HBOT administration for the following conditions:

• Air and gas embolism
• Severe anemia when blood transfusion is contraindicated
• Severe burns
• Carbon monoxide poisoning
• Crush injury
• Decompression sickness
• Gas gangrene
• Sudden, complete idiopathic hearing loss
• Severe cellulitis and osteomyelitis
• Radiation injury
• Skin grafts or flaps at risk of tissue death
• Central retinal artery occlusion
• Nonhealing wounds and diabetic foot ulcers (FDA Hyperbaric Oxygen Therapy Get the Facts)

Issues of Concern

HBOT induces generalized vasoconstriction in healthy blood vessels. Exposure to oxygen at partial pressures of at least 2 atmospheres absolute (ATA) triggers arteriolar vasoconstriction and increases systemic vascular resistance. The primary mechanism involves reduced nitric oxide production in the endothelium. The hyperoxic environment accelerates the oxidation of nitric oxide radicals, diminishing their vasorelaxant effect. Research also suggests that HBOT alters other vasodilators, such as prostaglandins, further contributing to vasoconstriction. Additionally, central vasoregulation plays a role, as hyperoxia is believed to activate the sympathetic nervous system, promoting vasoconstriction. Increased sympathetic activity has been observed through elevated plasma epinephrine and norepinephrine levels in these conditions.[4][5][6][7]

The net increase in arteriolar vasoconstriction and systemic vascular resistance reduces tissue edema while enhancing oxygen delivery. Although vasoconstriction partially restricts blood flow, plasma hyperoxygenation compensates by increasing overall oxygen transport. The central nervous system responds uniquely, as short-term hyperoxia induces cerebral vasoconstriction, further reducing blood flow. However, despite this reduction, hyperoxia ensures that the cerebrum still receives more oxygen than it would under normal conditions.[8]

HBOT may induce vagal activity, leading to sinus bradycardia. This vagal activation is thought to result from stimulating neurons in the dorsal motor nucleus of the vagus and the nucleus solitarius, key components of the brainstem's cardioinhibitory center. These structures contribute to hyperbaric reflex bradycardia.

Electrocardiogram analysis has shown increased RR-interval variability and high-frequency variability, which are interpreted as evidence of enhanced parasympathetic activity and vagal tone. Another proposed mechanism involves a nitrogen-dependent β-blockade of the heart, though strong evidence for this phenomenon remains lacking.

Bradycardia associated with HBOT appears to result from both increased oxygen levels and elevated pressure. Hyperoxia plays the primary role in initiating and maintaining bradycardia, but a measurable nonoxygen-dependent component is also linked to hyperbaric pressure. Both factors contribute to the overall effect. However, some evidence suggests that HBOT-induced bradycardia may not be driven by vagal activation, leaving the exact mechanisms open to debate.[9]

Other cardiovascular effects of hyperbaric hyperoxic conditions include reductions in cardiac output, stroke volume, and ventricular contractility. The decrease in cardiac output is primarily attributed to hyperoxia-induced bradycardia, though slightly reduced cardiac contractility may also contribute. In most patients, blood pressure remains stable during HBOT.

Mitochondrial respiratory rate plays a crucial role in myocardial function by influencing adenosine triphosphate (ATP) production during oxidative phosphorylation. Mitochondrial phosphorylation is dependent on oxygen tension, and hyperbaric hyperoxia can supply oxygen to areas of the myocardium and extracardiac tissues with low oxygen levels. Ensuring adequate oxygenation enables continued energy production, supporting the physiological function of the myocardium and similarly vital tissues.[10][11]

A baroreflex-mediated mechanism primarily links the cardiovascular responses to HBOT, including vasoconstriction, arterial hypertension, bradycardia, and reduced cardiac output. HBOT-induced vasoconstriction triggers the baroreflex, which acts through the vagal parasympathetic system to cause significant bradycardia without marked decreases in regional or systemic vascular resistance. Hyperoxic vasoconstriction activates mechanoreceptors in the aortic arch and carotid sinuses, the major baroreceptors. The afferent signals from these receptors stimulate central nervous system responses that suppress sympathetic activity and promote parasympathetic outflow.

Increased systemic vascular resistance, particularly in patients with left ventricular dysfunction, may lead to pulmonary edema. However, at least one study found that mild impairment of ejection fraction (< 40%) was relatively safe.[12]

Exposure to hyperbaric environments may occasionally cause electrical disturbances in the heart. Arrhythmias in these conditions are believed to result from increased vagal tone and heart distension due to blood redistribution into the chest. The increased hydrostatic pressure from HBOT also reduces myocyte excitability and conduction by directly affecting the myocardial cell membrane. Additionally, alterations in cardiac excitation-contraction coupling may contribute to arrhythmias.

The most common conduction abnormality observed is QT interval prolongation, which correlates with the degree of bradycardia and is more pronounced at lower heart rates. Clinical studies have also noted an increased incidence of junctional escape rhythms and isolated premature beats. However, these conduction abnormalities are generally of minimal physiological consequence to the patient.

Neovascularization is another critical aspect of HBOT. Angiogenesis depends on the fibroblast’s secretory function, which creates a matrix that capillary buds can invade. An essential component of this process is a gradient of well-oxygenated to near-anoxic tissues. Vascular endothelial growth factor (VEGF) is the primary growth factor responsible for initiating the processes leading to new blood vessel formation. VEGF is induced by oxygen and increases with higher oxygen tensions.

HBOT improves red blood cell (RBC) elasticity and reduces platelet aggregation. Additionally, the plasma’s ability to carry dissolved oxygen to areas that RBCs cannot reach contributes to better oxygenation of hypoxic tissues in various circulatory disorders.

During or after HBOT, patients with a history of congestive heart failure (CHF), whether with reduced (HFrEF) or preserved (HFpEF) ejection fraction, may develop symptoms of cardiac insufficiency due to pulmonary vascular congestion. However, these individuals often complete the treatment after medical optimization and close monitoring of any pharmacological or clinical changes during the session. Clinicians must closely observe the patient's respiratory and cardiac symptoms throughout the treatment, investigating emerging concerns to rule out acute or subacute heart failure.[13]

Additionally, potential mechanical adverse effects associated with HBOT, such as lung collapse, middle ear rupture, sinus damage, and changes in vision, should be considered. However, the therapy typically lasts no more than 2 hours.

Pretreatment optimization of cardiac function, including careful management of fluid status, use of appropriate medications, and addressing risk factors for myocardial ischemia or heart failure, can help prevent cardiovascular complications that can potentially arise from HBOT and improve patient outcomes. Adjusting treatment parameters, including pressure and session duration, may be necessary in some cases.

Clinical Significance

Vasoconstriction-induced reduction in blood flow leads to a corresponding decrease in edema. This reduction in vasogenic edema is observed in posttraumatic conditions such as crush injuries, compartment syndromes, burns, and reimplantations. HBOT also reduces cytotoxic edema in the brain and spinal cord, as well as radiation-induced ischemia, by helping reestablish more normal redox potentials. The result is improved intracellular oxygen tension, which supports cell metabolic functions and helps retain water within the cell, decreasing the leakage of water from ischemic cells into extracellular spaces.

Edema can impair cell function by increasing the diffusion distance of oxygen from extracellular fluid to the cell and potentially collapsing microcirculation. Clinical applications of HBOT, where vasoconstriction improves outcomes, include crush injuries, gas gangrene, compartment syndromes, threatened flaps and grafts, burns, decompression sickness, and several off-label uses.

HBOT-induced angiogenesis has several clinical applications. Wound healing depends on adequate blood flow and oxygen supply, but certain wounds, such as diabetic ulcers and radiation-damaged tissues, often have impaired circulation, hindering the healing process. HBOT not only increases oxygen access to damaged tissue through plasma saturation but also stimulates new blood vessel formation by activating transcription factors like VEGF. Additionally, HBOT-induced angiogenesis and fibroplasia have been shown to promote healing in radiated tissue, which does not spontaneously revascularize due to its unique wounding pattern.

HBOT is also a valuable adjunct in treating acute blood loss anemia, especially for patients who cannot receive blood replacement for medical or religious reasons. The hyperbaric hyperoxic environment accelerates hemoglobin synthesis and enhances oxygen delivery throughout the body despite reduced oxygen-carrying capacity due to anemia. This mechanism helps patients maintain oxygenation while they regenerate RBCs. HBOT is already used in offshore commercial diving for acute blood loss situations as a bridge until blood transfusions become available.

Debate continues regarding the effectiveness of HBOT in acute coronary syndrome. Physiologically, hyperbaric oxygen seems to preserve myocardial function and reduce mortality in acute myocardial infarction. However, studies have shown either no effect or only minor contributions to overall outcomes. The reasons for these inconclusive findings remain unclear, though ongoing research is exploring the topic.

HBOT is also used as an adjunctive treatment for peripheral vascular disease through several mechanisms. Hyperbaric oxygen enhances oxygen supply to ischemic or hypoxic tissues with marginal perfusion and improves cellular metabolism impaired by hypoxia. Hyperbaric oxygen alleviates ischemic effects by promoting angiogenesis and healing. Several pathways contribute to pain relief for patients with peripheral vascular disease, including increasing endorphins' affinity for receptor sites. HBOT also significantly reduces postischemic edema, with effects that persist after treatment.

HBOT improves cardiovascular outcomes through various mechanisms. This therapy addresses endothelial dysfunction by promoting angiogenesis, increasing nitric oxide bioavailability, reducing vascular resistance, and supporting endothelial glycocalyx integrity. HBOT stimulates the release of endothelial progenitor cells, which are crucial in maintaining vascular health and repairing damaged endothelium. Additionally, HBOT reduces inflammation by upregulating protective enzymes like superoxide dismutase and catalase. These enzymes are activated by an increased adaptive antioxidant response, which is driven by a regulated increase in reactive oxygen and nitrogen species.[14] A recent animal study demonstrated that a short course of HBOT improves cardiac function.[15]

HBOT, when initiated within 90 days of hospitalization for chronic osteomyelitis, reduces the risk of all-cause mortality and stroke at 1-year follow-up but increases the risk of myocardial infarction. A study involving patients with diabetes showed statistically significant changes in troponin I levels and QT and QTc intervals, although these changes did not reach clinical significance.[16] Patients with known coronary artery disease risk factors should receive specialized care from physicians.[17]

Enhancing Healthcare Team Outcomes

HBOT clearly has detrimental effects on the cardiovascular system, particularly after repeated sessions. Little evidence suggests that a single session impacts the cardiovascular system. Therefore, patients undergoing repeated treatments should follow up with a cardiac nurse, cardiologist, and internist to assess for cardiac symptoms. Preventable risk factors for cardiac disease should be minimized, and patients should be encouraged to maintain a healthy diet, exercise regularly, and avoid smoking. Healthcare workers should refrain from prescribing HBOT without a valid reason, and all members of the interprofessional team must be on the same page regarding the applications of this therapy.