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.
Arvesen
A
A
Division for Environmental Toxicology, Norwegian Defence Research Establishment, Kjeller, Norway.
Maehlen
J
J
Rosén
L
L
Aas
P
P
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