Protective effects of hyperbaric oxygen therapy (HBO2) in cardiac care--A proposal to conduct a study into the effects of hyperbaric pre-conditioning in elective coronary artery bypass graft surgery (CABG).

We review and report on accumulated data showing the benefits offered by hyperbaric oxygen (HBO2) therapy as an adjunct in the treatment of coronary artery bypass graft (CABG) patients. It has been shown that ischemia-reperfusion injury is deleterious to the myocardium, causing left ventricular dysfunction, structural damage to the myocytes and endothelial cells, myocardial stunning, reperfusion arrhythmias and potentially irreversible injury. There is a substantial body of evidence pointing to the role of HBO2 in mitigating the harmful effects of ischemia-reperfusion injury. Specifically, we review evidence from a number of studies which clearly point to both clinical and cost benefits HBO2 offers when used to precondition non-emergent patients having on-pump coronary arterial bypass graft surgery. Study data show that adding adjunctive HBO2 into the plan of care leads to improved myocardial function, reduces length of stay in the ICU, and limits post-surgical complications. Further, it has only minimal impact on the presurgical preparation, i.e., time must be allowed for the hyperbaric treatment(s), and no role in the surgery or post-surgical care of the patient. The studies pointing to clinical and cost benefit of preconditioning have been conducted outside the United States. Given the pressure on costs in all areas of health care, it seems that a therapeutic approach, which has been shown to be of benefit in both animal and human trials over the course of many years, should attract funding for a properly structured study designed to test whether significant and simultaneous improvements in clinical outcomes and cost reductions can be achieved within the framework of a U.S. healthcare facility.

A combination of radiotherapy, nitric oxide and a hyperoxygenation sensitizing protocol for brain malignant tumor treatment.

Brain malignant tumor such as glioblastoma is a challenging medical and surgical problem. In spite of surgery, radiotherapy and chemotherapy, the prognosis is still very poor. The limitations of currently available treatment modalities to cure or significantly prolong and improve the quality of life should stimulate rigorous research and studies to combat brain malignant tumors. While precision radiotherapy to reduce tumor size and ameliorate symptoms is still the standard of care, tumor sensitivity to radiation is compromised by low oxygen tensions and a necrotic tumor center. We propose to take advantage of the fact that elevated oxygen increases sensitivity of tumor cells to radiation. A specific application of hyperbaric oxygen (HBO(2)), using nitric oxide (NO) donors and inducers (such as L-arginine, dinitrite or tocopheryl succinate) and ascorbic acid to dilate blood vessels, should permit oxygen tensions in the range of 1000 mmHg to diffuse into the cells and thus increase sensitivity to radiation. This should permit doses that are low enough to cause the death of tumors cells yet minimize injury to brain tissue near the tumor and induced neurological sequelae.

Hyperbaric oxygen and lymphoid system function: a review supporting possible intervention in tissue transplantation.

This review addresses the many ways that hyperbaric oxygen (HBO2) has been found to mitigate immune reactions, many of which are involved in rejection of allograft transplants, and thus offers a rationale for its possible use as an adjunct to help preserve and protect transplanted tissues. Rejection may involve both immunological reactions of the lymphoid system, or lymphoid-independent damage from trauma or other factors, including reperfusion injury. Lymphoid-induced damage involves cellular elements such as CD4 and macrophage cell types, as well as both proinflammatory and inhibitory cytokines. Cytokines such as TNFs and interleukins activate T-cells and macrophages, resulting in endothelial damage and its consequences. The immunosuppressive effects of HBO2 include suppression of autoimmune symptoms, decreased production of IL-1 and CD4 cells, and increased percentage and absolute number of CD8 cells. HBO2 normalizes cell-bound immunity and decreases the serum concentration of immune complexes. Studies have shown MHC class I expression to be altered when cultures were exposed to HBO2, so as to become undetectable by monoclonal antibodies or cytotoxic T lymphocytes. HBO2 has been used in support of replanted rabbit ear grafts, spinal cord tissue transplants, dislocated young permanent teeth in children, replanting of fingers, free fibula reconstruction of segmental mandibular resections, autogenous free bone grafts, transplantations of the cornea, and liver transplants. In addition to its specific effects on the immune system, HBO2 improves tissue oxygenation, reduces free radical damage during reperfusion, maintains marginally ischemic tissue, and accelerates wound healing. These properties make HBO2 a promising intervention to be tested in transplantation recipients.

Influences of hyperbaric oxygen on blood pressure, heart rate and blood glucose levels in patients with diabetes mellitus and hypertension.

BACKGROUND: We investigated the influences of hyperbaric oxygen (HBO(2)) on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and blood glucose level (BGL). METHODS: Forty one patients with hypertension (HTN), diabetes mellitus (DM), HTN and DM and/or no HTN or DM underwent HBO(2) sessions (15-40 sessions for each patient). SBP, DBP, HR and BGL (for diabetics) were recorded before and after each session. RESULTS: HBO(2) caused significant elevation in SBP (11%) and DBP (12%) and a decrease in HR (18%) (p <0.001). Patients with DM and HTN showed higher elevation in SBP and DBP. HBO(2) lowered BGL by 23% (p <0.001). When basal BGL was in the range of 120-170 mg/dl, it dropped to <100 mg/dl in 31/60 treatment sessions (52%). When basal BGL was <120 mg/dl it dropped to <70 mg/dl in 8/34 sessions. There was a possibility of lowered BGL when basal BGL was <170 mg/dl and a marked reduction in BGL occurred when basal BGL was <120 mg/dl. HBO(2) caused a marked elevation in SBP and DBP when basal SBP was >140 mmHg. Critical elevation was obtained when SBP was >160 mmHg. The use of beta blockers caused significant elevation of blood pressure while reducing HR. CONCLUSIONS: HBO(2) causes elevation of blood pressure and lowering of HR and BGL, which were augmented in the presence of HTN, DM, or beta blocker. The use of beta blockers for the management of HTN should be avoided during HBO(2) therapy.

Phototherapy and malignancy: possible enhancement by iron administration and hyperbaric oxygen.

Photodynamic therapy (PDT) is a new therapeutic approach for the treatment of malignant tumors. Hyperbaric oxygen (HBO(2)) shows beneficial effects in various modalities of cancer interventions. Tumor cells tend to accumulate large amount of iron. There is interaction between tissue content of oxygen, iron, free radical production and tissue damage. Accumulation of intracellular iron is necessary for the production of oxygen radicals. HBO(2) increases tissue oxygen and hydrogen peroxide production in the cells. Malignant cells require iron, and exhibit more transferrin receptors. The photodynamic sensitization of human leukemic cells is achieved with accumulation of porphyrins stimulated by 5-aminolaevulanic acid (ALA) plus hemin. Further, a significant improvement in tumor response is obtained when PDT is delivered during hyperoxygenation. When PDT is combined with hyperoxygenation, the hypoxic condition is improved and the cell killing rate at various time points after PDT is significantly enhanced. Photosensitization with use of porphyrins is used with HBO(2) and PDT for treatment of certain tumors. PDT with ALA is used for treatment of actinic keratosis (AK). The combination of iron administration (by injection or oral rout), hemin, or transferrin, as a source for iron, HBO(2) as a source of oxygen under pressure and PDT as a source of generating free-radical tissue damage may be useful in the treatment of tumors. The possibility of combining HBO(2), iron, light and local photosensitizers to overcome skin tumors deserve extensive laboratory and clinical research work. Conclusively, iron, HBO(2), and PDT may have synergistic effect to hamper tumor cells.

Effects of hyperbaric oxygen on inflammatory response to wound and trauma: possible mechanism of action.

There is growing interest in expanding the clinical applications for HBO2 (hyperbaric oxygen therapy) into new medical and surgical fields. The pathophysiology of response towards wounds, infection, trauma, or surgery involves various chemical mediators that include cytokines, prostaglandins (PGs), and nitric oxide (NO). The beneficial role played by HBO2 in wound healing, carbon monoxide poisoning, decompression sickness, and other indications is well documented. However, the exact mechanism of action is still poorly understood. This review addresses the effects of HBO2 on PGs, NO, and cytokines involved in wound pathophysiology and inflammation in particular. The results of this review indicate that HBO2 has important effects on the biology of cytokines and other mediators of inflammation. HBO2 causes cytokine down-regulation and growth factor up-regulation. HBO2 transiently suppresses stimulus-induced proinflammatory cytokine production and affects the liberation of TNFa (tumor necrosis factor alpha) and endothelins. VEGF (vascular endothelial growth factor) levels are significantly increased with HBO2, whereas the value of PGE2 and COX-2 mRNA are markedly reduced. The effect of HBO2 on NO production is not well established and more studies are required. In conclusion, cytokines, PGs, and NO may play a major role in the mechanism of action of HBO2 and further research could pave the way for new clinical applications for HBO2 to be established. It could be proposed that chronic wounds persist due to an uncontrolled pathological inflammatory response in the wound bed and that HBO2 enhances wound healing by damping pathological inflammation (anti-inflammatory effects); this hypothetical proposal remains to be substantiated with experimental results.

Hyperbaric oxygen and malignancies: a potential role in radiotherapy, chemotherapy, tumor surgery and phototherapy.

Over the past 40 years, hyperbaric oxygen (HBO2) therapy has been recommended and used in a wide variety of medical conditions. In the 1950s, HBO2 was first used as a treatment, in addition to radiation, for head and neck cancers and cervical cancer. Many studies have been conducted to investigate possible therapeutic effects HBO2 as part of cancer management. Evidences showed that HBO2 improved tumor oxygenation, and treatment with HBO2 during irradiation has been shown to improve the radiation response of many solid tumors. It was used for delayed radiation injuries for soft tissue and bony injuries, for symptomatic radiation reactions of the urinary bladder and the bowel, for laryngeal radionecrosis, for radiation-induced optic neuropathy, for radiation-induced proctitis and for radiation-induced necrosis of the brain. HBO2 also increases sensitivity to chemotherapy. A significant improvement in tumor response was obtained when photodynamic therapy (PDT) was delivered during hyperoxygenation. These studies were extensively reviewed and rational scientific basis for further investigations was discussed. The possibility of combining HBO2, PDT and photosensitizers to overcome primary and secondary carcinoma deserve extensive laboratory and clinical research works. HBO2 is a relatively benign with few contraindications, even for active cancer patients.

Hyperbaric oxygen in the treatment of patients with cerebral stroke, brain trauma, and neurologic disease.

Hyperbaric oxygen (HBO) therapy has been used to treat patients with numerous disorders, including stroke. This treatment has been shown to decrease cerebral edema, normalize water content in the brain, decrease the severity of brain infarction, and maintain blood-brain barrier integrity. In addition, HBO therapy attenuates motor deficits, decreases the risks of sequelae, and prevents recurrent cerebral circulatory disorders, thereby leading to improved outcomes and survival. Hyperbaric oxygen also accelerates the regression of atherosclerotic lesions, promotes antioxidant defenses, and suppresses the proliferation of macrophages and foam cells in atherosclerotic lesions. Although no medical treatment is available for patients with cerebral palsy, in some studies, HBO therapy has improved the function of damaged cells, attenuated the effects of hypoxia on the neonatal brain, enhanced gross motor function and fine motor control, and alleviated spasticity. In the treatment of patients with migraine, HBO therapy has been shown to reduce intracranial pressure significantly and abort acute attacks of migraine, reduce migraine headache pain, and prevent cluster headache. In studies that investigated the effects of HBO therapy on the damaged brain, the treatment was found to inhibit neuronal death, arrest the progression of radiation-induced neurologic necrosis, improve blood flow in regions affected by chronic neurologic disease as well as aerobic metabolism in brain injury, and accelerate the resolution of clinical symptoms. Hyperbaric oxygen has also been reported to accelerate neurologic recovery after spinal cord injury by ameliorating mitochondrial dysfunction in the motor cortex and spinal cord, arresting the spread of hemorrhage, reversing hypoxia, and reducing edema. HBO has enhanced wound healing in patients with chronic osteomyelitis. The results of HBO therapy in the treatment of patients with stroke, atherosclerosis, cerebral palsy, intracranial pressure, headache, and brain and spinal cord injury are promising and warrant further investigation.