Early and late functional and histopathological perturbations in the rabbit ear-artery following local cold injury.
BACKGROUND
These experiments aimed to study the in vivo short and long term neurovascular regeneration after frostbite.


METHODS
The rabbit central ear-artery was used as the experimental model. The effects on the noradrenergic innervation of the artery were measured in isolated vascular ring segments the first day and 2, 3-4, and 8-10 or 10-20 weeks following freezing at -9 degrees C or -18 degrees C for 15 min with slow rewarming for 7 min at room temperature.


RESULTS
Two days after freezing the sympathetic nerves were completely degenerated, as observed with glyoxylic acid-induced fluorescence. The vascular isometric tension responses to exogenous noradrenaline and endogenously released noradrenaline by electrical stimulation in vitro were abolished. A varying degree of necrosis of the vascular wall was observed. Two weeks after freezing at -18 degrees C in vitro responses to exogenous noradrenaline and electrical stimulation were still abolished, then gradually approaching control levels after 10-20 weeks of in vivo regeneration. Eight and 10 weeks after injury at -9 degrees C increased vascular tension responses to exogenous noradrenaline was found. In spite of a long regeneration period the total uptake and the spontaneous and K+ (75 mM) evoked releases of [3H]noradrenaline were persistently decreased after frostbite at -18 degrees C, but they were regenerated to control levels already 10-20 weeks after -9 degrees C. Regeneration of noradrenergic nerve function, expressed as [3H]noradrenaline uptake and release and responsiveness to electrical stimulation, expressed as vascular contraction, was slower than the regeneration of the vascular smooth muscle. Myointimal hyperplasia developed in response to -9 degrees C and -18 degrees C frostbite. The uptake and the K+ evoked release of [3H]noradrenaline were particularly sensitive parameters for autonomic nerve function.


CONCLUSIONS
The present findings may demonstrate important neurovascular reactions to local frostbite and may explain human sequelae following frostbite.
Division for Environmental Toxicology, Norwegian Defence Research Establishment, Kjeller, Norway.
A
A
Arvesen
J
J
Maehlen
L
L
Rosén
P
P
Aas
D000320:Adrenergic Fibers / Q000473:pathology*; D000818:Animals; D001158:Arteries / Q000294:innervation / Q000473:pathology; D004431:Ear, External / Q000098:blood supply*; D005352:Fibromuscular Dysplasia / Q000473:pathology; D005627:Frostbite / Q000473:pathology*; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000294:innervation* / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000473:pathology
D009638:Norepinephrine