The Effect of Hyperbaric Oxygen on Ischemia–Reperfusion Injury

Abstract

The effect of hyperbaric oxygen is known to increase survival of ischemic tissue but its mechanism is not fully understood. The purpose of this study was to evaluate the effect of hyperbaric oxygen on a rat musculocutaneous flap versus ischemia-reperfusion injury, focusing on the mechanism involving the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) of endothelial cells and CD18 of neutrophils. A transverse rectus abdominis musculocutaneous (TRAM) flap (6 x 5 cm) supplied by a single superior epigastric vascular pedicle was elevated in 100 Sprague-Dawley rats. The rats were divided into 4 groups: group 0, sham (n = 10); group I, 4 hours of ischemia followed by reperfusion (n = 30); group II, 4 hours of ischemia and hyperbaric oxygen (100% oxygen, 2.5 atm absolute, during the last 90 minutes of ischemia before reperfusion) followed by reperfusion (n = 30); and group III, 4 hours of ischemia followed by reperfusion and hyperbaric oxygen (100% oxygen, 2.5 atm absolute, after reperfusion for 90 minutes; n = 30). The study consisted of gross examination for flap survival, histology, immunohistochemical staining, myeloperoxidase assay, flow cytometric study of CD18, and Northern blot analysis on ICAM-1 messenger ribonucleic acid expression. Gross measurement of the flap showed increased survival in groups II and III compared with group I (P < 0.05). The leukocytes adherent to the endothelium were counted at 24 hours and on day 5. Group I leukocytes were significantly increased compared with groups II and III (P < 0.05). The myeloperoxidase assay of TRAM flaps at 24 hours revealed a significant increase in group I compared with groups II and III (P < 0.05). The expression of CD18 was similar between groups I, II, and III. Immunohistochemical staining for ICAM-1 and Northern blot analysis on ICAM-1 messenger ribonucleic acid showed decreased expression in groups II and III compared with group I. Throughout the analysis, groups II and III did not show any significant differences. These results suggests that hyperbaric oxygen reduces the accumulation of leukocytes in the TRAM flap, but not enough to prevent adhesion of neutrophils on endothelial cells; ischemia-reperfusion injury increases the expression of CD18 and ICAM-1 and causes increased adhesion of leukocytes on the endothelium; hyperbaric oxygen does not alter the expression of CD18 but decreases the expression of ICAM-1; and the point of application for hyperbaric oxygen, whether applied before or after reperfusion, did not show any differences in outcome. In conclusion, the application of hyperbaric oxygen against ischemia-reperfusion injury increases flap survival and the beneficial effect may be explained by a protective mechanism involving downregulation of ICAM-1 on endothelial cells.

Spatio-temporal course of macrophage-like cell accumulation after experimental embolic stroke depending on treatment with tissue plasminogen activator and its combination with hyperbaric oxygenation

“…Furthermore, HBO was found to decrease the accumulation of neutrophils, 45,46 possibly based on a HBO-related reduction of ICAM-1. 80,81 In the present study, the accumulation of macrophage-like cells in the ischaemic area increases in a nearly identical way from 24 h to 7 days irrespective of treatment (see Figure 2A), which means that a combined application of HBO at 2.4 ata and tPA does not encompass a decreased inflammatory response during the first 7 days following experimental stroke. Similarly, Hjelde et al reported neutrophil accumulation after permanent MCAO in rats following treatment with HBO at 2.0 ata or room air under ambient pressure.…”

Effects of hyperbaric oxygen and N-acetylcysteine in survival of random pattern skin flaps in rats

“…Hong JP[14] showed that when hypoxic tissue is exposed to HBO, there is an increase in pO 2 in the plasma and a reduction in pO 2 , and the rate of diffusion of oxygen increases.…”

Effect of hyperbaric oxygen on survival of composite grafts in rats

“…Hong et al [1] found that HBO applied before or after reperfusion made no difference in outcome, but increased the area that survived in TRAM flaps in rats on both situations. Storage of free flaps in an HBO chamber for a few hours reduced the accumulation of hypoxanthine, and increased the area of survival in rats [10].…”

“…It is presumed that HBO prevents injury mediated by white blood cells from oxygen radicals and peroxidation. Various cellular modifications have been reported as a consequence of treatment with HBO [1]. Composite grafts have an important role in reconstructive procedures, but the exact size of a composite graft that will survive completely has not been laid down.…”