Hyperbaric oxygen therapy to treat diabetes impaired wound healing in rats

Abstract

Wound healing in diabetes is frequently impaired and its treatment remains a challenge. Hyperbaric oxygen therapy (HBOT) receives a wide attendance and is often used as a last resort treatment option, however, its effectiveness for many conditions is unproven. We tested the effect of HBOT on healing of diabetic ulcers in an animal experimental setting. Experimental diabetes was induced by intraperitoneal injection of streptozotocin. Four weeks after diabetes induction, rats were ulcerated by clamping a pair of magnet disks on the dorsal skin for 16 h. After magnet removal, the animals received HBOT, daily on weekdays, for 4 weeks. To examine the effect of HBOT on diabetes impaired wound healing, the degree of wound tissue perfusion, inflammation, angiogenesis, and tissue breaking strength were evaluated. HBOT effects on the degree of inflammation and number of blood vessels could not be observed. HBOT improved the tissue breaking strength of the wound, however, this did not reach statistical significance. Twenty hours after ending the HBOT, a significantly improved oxygen saturation of the hemoglobin at the venous end of the capillaries and the quantity of hemoglobin in the micro-blood vessels was measured.

Figure 1. Macroscopic images of control and HBOT wounds at post-wounding days 7 and 29.

Figure 2. Histological staining of control and HBOT wounds at post-wounding days 7 and 29.

A–D) H&E staining. E–H) CD34 immunohistochemistry. I+J) CD68 immunohistochemistry.

Figure 3. The effect of HBOT on blood flow, oxygen saturation of the hemoglobin at the venous end of the capillaries (SO2), and the quantity of hemoglobin in the micro-blood vessels (rHB).

Effects were measured, in control skin and at the wound edge in control and HBOT animals, approximately 20 hours after the last HBOT session. Data are presented as means ± SEM. P-values indicate differences between the respective control group and HBOT group. AU = artificial units.

Figure 4. The effect of HBOT on blood flow, oxygen saturation of the hemoglobin at the venous end of the capillaries (SO2), and the quantity of hemoglobin in the micro blood vessels (rHB).

Effects were measured in control and HBOT animals, approximately 20 hours after the last HBOT session, and expressed as a percentage of the values of non-wounded skin in the respective animal. Data are presented as means ± SEM. P-values indicate differences between the respective control group and the HBOT group.

Figure 5. Ratio of the skin breaking strength of normal skin and wounded skin in diabetic rats at day 29 post wounding.

Data are presented as means ± SEM. P-values indicate differences between the control group and the HBOT group.