Response of blood vessels in vitro to hyperbaric oxygen (HBO): modulation of VEGF and NO(x) release by external lactate or arginine.

Hyperbaric oxygen therapy (HBO) is suggested to promote angiogenesis during wound healing, but the mechanisms involved are not understood. This study used a novel isolated blood vessel preparation to explore the effects of air, normobaric oxygen or hyperbaric oxygen (2.2 ATA for 90 min) on the angiogenesis factor, vascular endothelial growth factor (VEGF), nitrite and nitrate (NO(x)), lactate dehydrogenase (LDH) and lactate release from the tissue in normal Krebs Ringer, and the Ringer supplemented with either l-arginine, or 15 mM lactate to mimic a wound environment, or both (l-arginine+lactate). The in vitro blood vessel preparation remained viable during all experiments. There were no effects of HBO treatment on any of the parameters measured in normal Krebs Ringer, but some treatment-dependent effects were observed in supplemented Krebs Ringer. In the lactate supplemented Krebs Ringer, medium LDH levels increased in response to either normobaric oxygen (NBO) or HBO, compared to air alone. There were also small, but statistically significant increases in total glutathione due to HBO treatment, compared to NBO or air in the lactate supplemented medium, and in the combined supplement. There were no effects of HBO on NO(x), changes in external medium lactate levels, or tissue VEGF in any of the Krebs Ringers tested. However, post treatment increases in VEGF were observed in the lactate supplemented medium, and for lactate release into the medium for the combined supplement. We conclude that HBO does not cause NO or VEGF production from the blood vessel in normal Krebs Ringer, but the data from supplemented medium show that the response of the tissue is subtly affected by the chemical environment around the blood vessel, and the tissue is more responsive to HBO when wound conditions are mimicked.