Hyperbaric oxygen, oxidative stress, NO bioavailability and ulcer oxygenation in diabetic patients

Hyperbaric oxygen therapy (HBO2) increases tissue oxygenation, thus serving as an adjunct therapy for diabetic wounds. However, in some patients there is insufficient increase in tissue O2.

To investigate the pathophysiology of insufficient HBO2 and the possible role of N-acetylcysteine (NAC).

Prospective, randomized, cross-over trial included 50 diabetic patients with non-healing ulcers. Each patient received two treatments with 100% oxygen/2ATA. NAC was administered i.v. at one of the two treatments. Basal and post-treatment peri-wound transcutaneous O2 (TcPO2) pressure, malondialdehyde (MDA), total anti-oxidant status (TAOS) and nitric oxide (NO) were assessed. An ulcer oxygenation increase above 200 mmHg was accepted as sufficient.

During HBO2, 17 patients (34%) demonstrated insufficient increase in TcPO2. Concomitantly, their TAOS and NO decreased, while MDA increased. NAC administration attenuated these parameters, thus improving the HBO2 outcome. In those affected by NAC, the cure rate was 75%. By contrast, in 66% of patients with sufficient increase in TcPO2 TAOS was increased and MDA decreased irrespective of NAC administration. The cure rate in this subgroup was 82%.

Insufficient increase of ulcer oxygenation during HBO2 results from exaggerated oxidative stress and decreased NO bioavailability. NAC administration-induced modulation of both parameters and may improve ulcer oxygenation during HBO2.