Hyperbaric oxygen toxicity: role of thromboxane.

Area of Science:

• Pulmonary Medicine
• Toxicology
• Biochemistry

Background:

• Hyperbaric oxygen (100% O2 at 4 atm) induces significant pulmonary hypertension and lung injury in rabbits.
• This injury is associated with a marked increase in thromboxane B2 levels in alveolar lavage fluid.

Purpose of the Study:

• To investigate the role of thromboxane in hyperbaric oxygen-induced lung injury.
• To evaluate the protective effects of antioxidants and specific enzyme therapies against hyperbaric oxygen toxicity.

Main Methods:

• Rabbits were exposed to hyperbaric oxygen (100% O2, 4 atm) for 1 hour.
• Measurements included thromboxane B2 levels, pulmonary arterial pressure, lung weight gain, and aerosolized compound transfer rates.
• Therapeutic interventions included butylated hydroxyanisole (BHA), polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) and PEG-catalase, unconjugated SOD and catalase, indomethacin, and a thromboxane synthase inhibitor (UK 37,248-01).

Main Results:

• Hyperbaric oxygen exposure significantly increased thromboxane B2, pulmonary arterial pressure, lung weight gain, and lung permeability.
• Pretreatment with BHA completely prevented pulmonary hypertension and lung injury.
• Combined PEG-SOD and PEG-catalase therapy also completely abolished the adverse effects.
• Indomethacin and a thromboxane synthase inhibitor effectively eliminated pulmonary hypertension and edema.

Conclusions:

• Thromboxane plays a critical role in mediating hyperbaric oxygen-induced pulmonary hypertension and lung injury.
• Antioxidant and specific enzyme therapies, particularly those involving PEG-conjugated enzymes, offer significant protection against oxygen toxicity.
• Targeting thromboxane synthesis or action may be a viable therapeutic strategy for managing hyperbaric oxygen-induced lung damage.