Hyperbaric oxygen therapy provides a hundred percent concentration and at supra atmospheric pressures about 1.5-3 times higher than normal atmospheric pressure. This method is utilized for the healing of the body by ensuring more than adequate oxygen supply. However, both the high-pressure environment as well as the hyperoxygenation that is associated with hyperbaric oxygen treatments (HBOT) have numerous consequences on the human cardiovascular system. Understanding these mechanical and physiological changes plays an important role in how HBOT is utilized.[1][2][3]

HBOT initiates generalized vasoconstriction of healthy blood vessels. Exposure to partial pressures of oxygen of at least 2 ATA is known to induce arteriolar vasoconstriction and increase systemic vascular resistance. The main mechanism that leads to this vasoconstriction involves a reduction of nitric oxide production in the endothelium. The hyperoxic environment leads to increased oxidation of nitric oxide (NO) radicals produced by the endothelium, thus leading to a loss of the vasorelaxant effect. Additionally, some research has shown that HBOT leads to alterations in other vasodilator compounds, such as prostaglandins, which contribute to the net vasoconstriction effect. Another contributing factor involves central vasoregulation. It is thought that hyperoxia stimulates the sympathetic nervous system to promote vasoconstriction. Humans have been shown to have an augmentation of sympathetic nervous system activity, measured by the levels of plasma epinephrine and norepinephrine during these conditions.[4][5][6][7]

The net increase in arteriolar vasoconstriction and systemic vascular resistance leads to an overall decrease in tissue edema and increased tissue oxygenation. Although vasoconstriction partially impedes blood flow, the hyperoxygenation of the plasma results in an overall gain in delivered oxygen. The central nervous system (CNS) is unique, however, in that short-term hyperoxia causes increased cerebral vasoconstriction and furthers the reduction of blood flow. However, even with the reduction of cerebral blood flow, the cerebrum receives more oxygen than it would otherwise.

HBOT stimulates vagal activity leading to sinus bradycardia. The mechanism behind the vagal activation involves the stimulation of neurons in the dorsal motor nucleus of vagus and nucleus solitarius. These brainstem neurons play important roles in the cardioinhibitory center and underlie the hyperbaric reflex bradycardia. There is also an increase in RR-interval variability and high-frequency variability in electrocardiogram analysis. These findings are interpreted as indicating that HBOT leads to parasympathetic activity and increases vagal tone. It has been suggested that another factor leading to the slowed heart rate is a nitrogen-dependent beta-blockade of the heart. However, there is yet to be strong evidence for that claim. The bradycardia that is associated with HBOT is considered to be a result of both the increased oxygen and the increased pressure. Hyperoxia is notably the major factor responsible for initiating and maintaining the bradycardia. However, there is a measurable non-oxygen dependent bradycardia that is associated with hyperbaric pressures. Both forces play an important role in the bradycardia associated with HBOT.

Other cardiovascular effects of hyperbaric hyperoxic conditions include a reduction of cardiac output, stroke volume, and ventricular contractility. The reduction of cardiac output is thought to be primarily due to the hyperoxic induced bradycardia. However, slightly diminished cardiac contractility may also be a contributing factor. In most patients, blood pressure remains unchanged during HBOT. The mitochondrial respiratory rate is an essential component of myocardial function because it influences the production of adenosine triphosphate during oxidative phosphorylation. Mitochondrial phosphorylation depends on oxygen tension. The hyperbaric hyperoxic conditions can provide oxygen to areas of the myocardium (or other tissues) that have low oxygen tensions. This allows the cells to continue to generate energy and maintains the physiological capability of the myocardium or other tissues.[8][9]

A baroreflex-mediated mechanism primarily links the HBOT-induced cardiovascular responses of vasoconstriction, arterial hypertension, bradycardia, and reduced cardiac output. HBO-induced vasoconstriction triggers the baroreflex, and thus, acts via the vagal parasympathetic system to cause profound bradycardia without significant decreases in regional or systemic vascular resistance. The hyperoxic vasoconstriction activates mechanoreceptors located in the aortic arch and carotid sinuses which act as the major baroreceptors. The afferent discharges from these arterial baroreceptors evoke CNS responses that suppress sympathetic activity and promote parasympathetic outflow.

Exposure to hyperbaric environments has been shown to cause electrical activity disturbances in the heart occasionally. Arrhythmias under these conditions are believed to be due to an increase in vagal tone as well as heart distension from blood redistribution into the chest. The increased hydrostatic pressure from HBOT also decreases myocyte excitability and conduction by affecting the myocardial cell membrane directly. Additionally, alteration of cardiac excitation-contraction coupling may be another cause of arrhythmias. The most prominent conduction abnormality noted is QT interval prolongation. The QT prolongation is consistent with the level of bradycardia and is more prominent with decreasing heart rates. An increase in the incidence of junctional escape rhythms and isolated premature beats has also occasionally been measured in clinical studies. These conduction abnormalities, however, are fairly insignificant in terms of physiological consequences for the patient.

Neovascularization is another very important aspect of HBOT. Angiogenesis is dependent on the secretory function of the fibroblast laying down a matrix that can be invaded by capillary budding into it. The other essential component is a gradient of well-oxygenation to near anoxic tissues. VEGF is the main growth factor responsible for initiating the cascade of processes leading to new blood vessel formation. VEGF is induced by oxygen and has been shown to increase in level with increased oxygen tensions. HBO improves the elasticity of the RBC and reduces platelet aggregation. This, combined with the ability of the plasma to carry dissolved oxygen to areas where RBCs cannot reach, has a beneficial effect on the oxygenation of many hypoxic tissues in various circulatory disorders.

Lastly, it is also important to know the possible mechanical adverse effects associated with HBOT such as lung collapse, middle ear rupture, sinus damage, and changes in vision etc. The therapy usually does not last more than 2 hours. 

The reduction of blood flow secondary to vasoconstriction leads to a corresponding edema reduction. Reduction of vasogenic edema is seen in posttraumatic conditions such as crush injuries, compartment syndromes, burns, and reimplantations. It also reduces cytotoxic edema in the brain, spinal cord, and radiation-induced ischemia by helping to re-establish more normal redox potentials. The consequence is improved intracellular oxygen tensions which maintain cell metabolic functions to keep water in the cell. The result is decreased leakage of water from the ischemic cell to the extracellular spaces. Edema can be detrimental to cell function. It increases the diffusion distance of oxygen from the extracellular fluid to the cell. It also can cause the collapse of microcirculation. Some of the clinical applications of HBOT where vasoconstriction improves outcomes include crush injuries, gas gangrene, compartment syndromes, threatened flaps/grafts, burns, decompression sickness, as well as several other off-label uses.

HBOT angiogenesis has several clinical applications. Wound healing relies on adequate blood flow and oxygen supply. Certain types of wounds, such as diabetic ulcers or radiation damaged tissues, often have impaired circulation which dramatically affects the healing process. HBOT not only provides increased access of oxygen via plasma saturation to damaged tissue, but also encourages new blood vessel formation by activation transcription factors such as VEGF. Additionally, hyperbaric oxygen-induced angiogenesis and fibroplasia has been shown to promote healing to radiated tissue. This is especially useful because radiated tissue does not spontaneously revascularize due to their unique wounding pattern.

HBOT is a valuable adjunct when used early in the treatment of acute blood loss anemia in those who cannot receive blood replacement for medical or religious reasons. The hyperbaric hyperoxic environment accelerates hemoglobin synthesis and increases oxygen delivery throughout the body despite the reduced oxygen carrying capacity due to anemia. This mechanism can help keep patients without a blood transfusion while they regenerate RBCs on their own. HBOT is already being used in the offshore commercial diving realm for acute blood loss situations as a bridge until transfused units of blood become available.

There is still much debate as to whether or not HBOT appears to be helpful in acute coronary syndrome. Physiologically, it would make sense that hyperbaric oxygen preserves myocardial function and reduces mortality for acute myocardial infarctions. However, studies so far have demonstrated either no effect or only small contributions to the overall outcome. It is unclear as to why the data is inconclusive at this time, but more research on this topic continues.

HBOT is also used as a treatment adjunct for peripheral vascular disease through several mechanisms. Hyperbaric oxygen increases oxygen supply in the marginally perfused ischemic/hypoxic tissues and improves the cellular metabolism that has been impaired by hypoxia. It relieves the effects of ischemia by promoting angiogenesis and healing. A variety of different pathways help provide pain relief for patients with PVD including increasing the affinity of endorphins for receptor sites. HBOT significantly reduces postischemic edema, an effect that persists after treatment.