Experimental ischemic neuropathy: salvage with hyperbaric oxygenation.
Hyperbaric oxygenation is effective in augmenting the delivery of oxygen to tissue, but also causes oxidative stress. As part of our focus on improving peripheral nerve salvage from ischemic fiber degeneration, we evaluated whether hyperbaric oxygenation rescues peripheral nerve, rendered ischemic by microembolization, from ischemic fiber degeneration. The supplying arteries of rat sciatic nerve were embolized with microspheres of 14 microns diameter at moderate (2 x 10(6)) and high (5.6 x 10(6)) doses. Rats were randomized to receive hyperbaric oxygenation treatment (2.5 atm 100% oxygen for 2 hours/day for 7 days beginning within 30 minutes of ischemia), or room air. End points for the embolized limb were (1) behavioral scores (0-11 in increasing levels of limb function), (2) nerve action potential of sciatic-tibial nerve, (3) nerve blood flow, and (4) histological grade as percentage of fibers undergoing ischemic fiber degeneration (0 = < 5%; 1 = 5-25%; 2 = 26-50%; 3 = 51-75%; 4 = > 76%). Nerve blood flow and nerve action potential were uniformly absent and more than 90% of fibers had degenerated in both control and treatment groups receiving high doses. Control and treatment groups receiving moderate doses were well matched by level of ischemia (8.5 +/- 0.3 [N = 18] vs 7.7 +/- 0.4 ml/100 gm/min [N = 18], p > 0.05) but were significantly different by behavior score (5.6 +/- 0.7 vs 9.2 +/- 0.5 [N = 19], p < 0.001), nerve action potential (1.4 +/- 1.0 vs 3.9 +/- 0.5 [N = 6], p < 0.05), and histology (2.4 +/- 0.4 [N = 5] vs 0.8 +/- 0.5 [N = 4], p < 0.05). On single teased fiber evaluation, the predominant abnormality was E (axonal degeneration). We conclude that hyperbaric oxygenation will effectively rescue fibers from ischemic fiber degeneration, providing the ischemia is not extreme.
Kihara
M
M
Department of Neurology, Mayo Foundation, Rochester, MN 55905.
McManis
P G
PG
Schmelzer
J D
JD
Kihara
Y
Y
Low
P A
PA
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004487:Edema / Q000473:pathology; D006801:Humans; D006931:Hyperbaric Oxygenation; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000098:blood supply*; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012584:Sciatic Nerve / Q000098:blood supply / Q000473:pathology / Q000502:physiology