Hyperbaric oxygen induces basic fibroblast growth factor and hepatocyte growth factor expression, and enhances blood perfusion and muscle regeneration in mouse ischemic hind limbs.
BACKGROUND
It is not clear how hyperbaric oxygen therapy (HBO) affects ischemia-induced pathophysiological responses such as angiogenesis and skeletal muscle regeneration. In the present study the effects of HBO on the functional and morphological recovery of ischemic hind limbs, blood perfusion and the local production of angiogenic growth factors were studied in a mouse model.


RESULTS
Mice were placed in pure oxygen under 3 atm for 1 h/day for 14 days after the removal of a segment of the left femoral artery. HBO-treated mice showed better functional recovery and greater blood flow in the ischemic hind limb than untreated mice. Histological examination revealed unatrophied muscle fibers with islands of small regenerating muscle cells only in HBO-treated mice. Regeneration of muscle was confirmed by the increase in myf5 mRNA. The amount of mRNA for vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) was slightly increased in the ischemic hind limbs. HBO eliminated the increase in VEGF mRNA. In contrast, the amount of mRNA for bFGF and HGF was further increased by HBO treatment. HBO transiently increased early growth response protein 1 (Egr-1) in the ischemic hind limbs.


CONCLUSIONS
HBO accelerates the recovery of ischemic hind limbs by increasing the production of bFGF and HGF and by promoting muscle regeneration in mice.
Asano
Tetsuichi
T
Geriatrics and Vascular Medicine, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
Kaneko
Eiji
E
Shinozaki
Shohei
S
Imai
Yutaka
Y
Shibayama
Masaharu
M
Chiba
Tsuyoshi
T
Ai
Masumi
M
Kawakami
Akio
A
Asaoka
Hiroshi
H
Nakayama
Toru
T
Mano
Yoshihiro
Y
Shimokado
Kentaro
K
D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006931:Hyperbaric Oxygenation; D007511:Ischemia / Q000628:therapy*; D035002:Lower Extremity / Q000098:blood supply / Q000502:physiology; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology*; D018919:Neovascularization, Physiologic; D012038:Regeneration; D015424:Reperfusion
D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor