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Effect of renal denervation on the development of cellophane-wrap hypertension in rabbits.

The development of hypertension in rabbits with bilateral cellophane wrapping of the kidneys was studied in animals with and without surgical denervation of the kidneys. Mean arterial pressure was measured before and 14 and 28 days after surgery. After 14 and 28 days of wrapping, mean arterial pressure had increased 12 +/- 3 mmHg and 31 +/- 3 mmHg in rabbits with innervated kidneys and 7 +/- 2 mmHg and 26 +/- 2 mmHg in rabbits with denervated kidneys, respectively. The increases in arterial pressure were significantly less in the denervated animals. In sham wrap animals, renal denervation also resulted in significantly lower arterial pressure than in sham wrap+sham denervated rabbits. Noradrenaline concentration of denervated kidneys averaged only 4% of that measured in kidneys subjected to sham denervation. The results show that renal denervation slightly attenuated the degree of hypertension developed following renal wrapping. Since renal denervation produced a similar small decrease in arterial pressure in normotensive rabbits it is suggested that the effect is non-specific and probably due to loss of efferent renal sympathetic nerves.

Animals↗

The age dependent effect of partial denervation of rat fast muscles on their activity.

In 3 or 18 day old Wistar rats the hindlimb muscles were partially denervated by cutting the L4 spinal nerve. Three months later, the effects of partial denervation of the fast extensor digitorum longus (EDL) muscle on the activity of its remaining motor units were studied using electromyographic (EMG) recordings in freely moving animals. In spite of a reduced number of motor units the amount of aggregate EMG activity was greater in the partially denervated EDL muscle in all experimental conditions. This increase was more obvious at rest than during exploratory behaviour, and was significantly greater in muscles that were partially denervated at 3 days than at 18 days of age. On the other hand, the effect of partial denervation on the EMG activity pattern during locomotion was similar in animals partially denervated at 3 or 18 days of age. Unlike in intact EDL, in the partially denervated EDL muscle the duration of the bursts was influenced by the step cycle duration. Thus, we conclude that although partial denervation of EDL muscle influences the amount and pattern of activity of the remaining undamaged motor units in all animals, some of the alterations of EMG activity were more pronounced in animals denervated at younger age.

Aging↗

Excretory function of intact kidney after contralateral denervation on unanaesthetized dogs.

The experiments were carried out on unanaesthetized dogs with exteriorized ureters. The left kidney was denervated. The function of the left and right kidneys was compared prior to and after furosemide administration, 0.2 mg/kg b. w. The function of the right intact kidney prior to and after left kidney denervation was also compared. The concentrations of sodium, potassium, chloride, calcium, magnesium, zinc, copper, urea, and creatinine in plasma and urine were determined. Denervation of the left kidney was followed by an increase of diuresis, calcium, and copper excretion from the denervated kidney. After furosemide administration the chloride excretion from the side of denervation was also observed to increase. The changes in the excretory function of the left kidney after denervation were not accompanied by changes in excretory function of right (intact) kidney. The excretory function of the intact kidney after denervation of contralateral kidney and furosemide administration did not differ from that prior to denervation and furosemide administration. In unanaesthetized dogs no changes in the excretory function of intact kidney were observed as a result of contralateral kidney denervation.

Animals↗

The effect of denervation diuresis on the severity of glycerol-induced acute renal failure in rats.

The results of several previous studies suggest that high urine flow rate has a protective effect in several models of experimentally induced acute renal failure. However, the methods employed to alter urine flow precluded a paired experimental design, left kidney vs. right kidney in the same experimental animal. The purpose of the present studies was to determine whether the unilateral diuresis that results from renal denervation has a protective effect on that kidney in glycerol-induced acute renal failure. Eight groups of rats were studied. The left kidneys of all were either denervated or sham-denervated; 3 to 5 days later, rats were injected with either 150 mM NaCl (controls) or glycerol; then either 3 or 24 hr after injection, renal function was measured in acute experiments. In saline-injected rats, the inulin clearances of right and left kidneys were virtually identical, whether the left kidney was denervated or not; however, in rats with denervated left kidneys, left kidney urine flow exceeded that of the right kidney whereas the opposite was true in rats with sham-denervated left kidneys. In contrast with saline-injected rats, there were highly significant differences in inulin clearances of right and left kidneys in glycerol-injected rats at both 3 and 24 hr after injection; left kidney inulin clearance exceeded that of the right in rats with denervated left kidneys, whereas right kidney inulin clearance exceeded that of the left in rats with sham-denervated left kidneys. Since the kidney with the higher urine flow had the higher inulin clearance at 3 and 24 hr after glycerol, whether or not the kidney was denervated, these results suggest that urine flow per se has a protective effect in glycerol-induced acute renal failure in rats.

Acute Kidney Injury↗

Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation.

The effects of prolonged denervation, independent from those of prolonged axotomy, on the recovery of muscle function were examined in a nerve cross-anastomosis paradigm. The tibialis anterior muscle was denervated for various durations by cutting the common peroneal nerve before a freshly cut tibial nerve was cross-sutured to its distal stump. Nerve regeneration and muscle reinnervation were quantified by means of electrophysiological and histochemical methods. Progressively fewer axons reinnervated the muscle with prolonged denervation; for example, beyond 6 months the mean (+/- SE) motor unit number was 15 +/- 4, which was far fewer than that after immediate nerve suture (137 +/- 21). The poor regeneration after prolonged denervation is not due to inability of the long-term denervated muscle to accept reinnervation because each regenerated axon reinnervated three- to fivefold more muscle fibers than normal. Rather, it is due to progressive deterioration of the intramuscular nerve sheaths because the effects of prolonged denervation were simulated by forcing regenerating axons to grow outside the sheaths. Fewer regenerated axons account for reinnervation of less than 50% of the muscle fibers in each muscle and contribute to the progressive decline in muscle force. Reinnervated muscle fibers failed to fully recover from denervation atrophy: muscle fiber cross-sectional area being 1171 +/- 84 microns2 as compared to 2700 +/- 47 microns2 after immediate nerve suture. Thus, the primary cause of the poor recovery after long-term denervation is a profound reduction in the number of axons that successfully regenerate through the deteriorating intramuscular nerve sheaths. Muscle force capacity is further compromised by the incomplete recovery of muscle fibers from denervation atrophy.

Anastomosis, Surgical↗

Structural and functional alterations caused at the extraneuronal level by sympathetic denervation of blood vessels.

The lateral saphenous vein of the dog and the rabbit ear artery were surgically denervated, by clamping the vessel or by removal of the superior cervical ganglion, respectively. Both procedures resulted in denervation of the vessels. The denervated, lateral saphenous vein was supersensitive to exogenous noradrenaline and inactivation of the amine (in oil immersion experiments) was slower in denervated vein strips than in control strips treated with cocaine. Incubation experiments with 3H-noradrenaline confirmed that denervated strips formed considerably fewer metabolites than control ones (in the absence or presence of cocaine) and that O-methylation of noradrenaline was reduced by about 50%. When the strips were incubated with 3H-isoprenaline, the denervated ones accumulated and metabolized isoprenaline to a lesser degree than control strips. Hydrocortisone did not reduce the accumulation of isoprenaline in the denervated vein and had only minor effects on O-methylation. The metabolism of noradrenaline and isoprenaline gradually recovered with time. In the ear artery, denervation was accompanied by a marked reduction in O-methylation, but not in accumulation, of isoprenaline. In both vessels there was a highly significant positive correlation between noradrenaline content and O-methylating capacity; in the saphenous vein accumulation of isoprenaline was also positively correlated to noradrenaline content. Morphological changes observed in the denervated vessels consisted essentially in dedifferentiation of smooth muscle cells (which attained larger dimensions, had an indented, large nucleus, augmented euchromatin and an increased amount of ribosomes), abundance of extracellular material and fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Purine agonists prevent trophic changes caused by sympathetic denervation.

Surgical denervation of the lateral saphenous vein of the dog causes marked extraneuronal changes, both of a morphological and functional type. In an attempt to investigate the factor(s) responsible for the trophic effects exerted by the sympathetic innervation on the dog saphenous vein we studied the effects of noradrenaline, adenosine, inosine and N-ethylcarboxamidoadenosine (NECA) on vascular tissue after sympathetic denervation. The saphenous vein was denervated using either surgical or chemical (6-hydroxydopamine, 6-OHDA) methods. Noradrenaline (0.1 microgram/kg per h), adenosine (10 micrograms/kg per h), inosine (10 micrograms/kg per h) or NECA (0.1 microgram/kg per h) were delivered continuously for 5 days through Alzet minipumps connected to the vein. 6-OHDA-induced denervation resulted in morphological changes similar to those described for surgical denervation. Smooth muscle cells and fibroblasts showed ultrastructural signs of increased synthetic activity and their size was significantly increased. In confirmation of earlier studies, constant i.v. infusions of noradrenaline did not prevent the morphological changes induced by denervation. Adenosine prevented the morphological changes induced by chemical or surgical denervation. Similarly to adenosine, infused NECA prevented the structural consequences of denervation. In contrast, inosine did not prevent the changes caused by surgical denervation. The results are compatible with an involvement of purines in the trophic effects of sympathetic innervation. Moreover, the effects of adenosine do not appear to be mediated by inosine.

Adenosine↗

Influence of peri-arterial hepatic denervation on the glycemic response to exercise in rats.

Exercise is known to increase hepatic glucose production. Previous studies have suggested that the sympathetic nerves only marginally contribute to this process. This study examined whether increased catecholamine response or increased adrenoceptor sensitivity might have affected previous results showing no effect of hepatic denervation on the increased hepatic glucose production during exercise. Hepatic sympathetic denervated rats, sham-operated rats and control rats were forced to swim against a counter current for 15 minutes. Denervations and sham operations were performed 9 days prior to swimming. The results show that denervation did not affect the changes in levels of blood glucose, plasma FFA, and catecholamines before, during and after swimming. Furthermore, hepatic adrenoceptor sensitivity was not altered in denervated rats, since intravenous infusions of epinephrine (20 ng/min) and norepinephrine (50 ng/min) similarly changed blood glucose and plasma FFA levels in liver-denervated, sham-operated and control rats. Thus, the increase in blood glucose levels during intravenous infusion of epinephrine and norepinephrine in the respective groups was 1.2 +/- 0.3 and 1.0 +/- 0.3 mmol/l (liver-denervated rats), 1.6 +/- 0.4 and 0.7 +/- 0.3 mmol/l (sham-operated rats) and 1.3 +/- 0.3 and 0.8 +/- 0.3 mmol/l (control rats), respectively. After adrenodemedullation, however, the rise of glucose levels during swimming in liver-denervated and control rats was completely abolished. Thus, the glucose response to swimming with and without adrenodemullation was 0.1 +/- 0.4 and 1.7 +/- 0.4 mmol/l in liver-denervated rats (P < 0.01) and -0.2 +/- 0.4 and 2.2 +/- 0.2 mmol/l in control rats (P < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Effect of hippocampal sympathetic ingrowth and cholinergic denervation on hippocampal phospholipase C activity and G-protein function.

Following cholinergic denervation of the hippocampal formation, via medial septal lesions, peripheral noradrenergic fibers, originating from the superior cervical ganglion, grow into the hippocampus. In previous studies, we have found that hippocampal sympathetic ingrowth and cholinergic denervation alone (animals with concurrent medial septal lesions and superior cervical ganglionectomy) alter phosphoinositide turnover and muscarinic cholinergic receptors in such a way as to suggest an alteration in coupling between the muscarinic cholinergic receptors and phosphoinositol turnover. To test this hypothesis we examined the effect of hippocampal sympathetic ingrowth and cholinergic denervation on phospholipase C activity, G-protein function and the whole receptor complex by measuring the amount of phosphoinositide hydrolysed in hippocampal membranes of the rat. Neither hippocampal sympathetic ingrowth nor cholinergic denervation was found to alter phospholipase C activity when activated by increasing concentrations of Ca2+. In dorsal hippocampus, cholinergic denervation, when compared to hippocampal sympathetic ingrowth and controls, was found to decrease the amount of phosphoinositol hydrolysed when stimulated with the GTP analog, guanosine-5'-O-(3-thiotriphosphate). When guanosine-5'-O-(3-thiotriphosphate) plus carbachol (1 mM) was utilized to stimulate the entire receptor complex, phosphoinositol hydrolysis was found to be decreased in the cholinergic denervation group as compared to both hippocampal sympathetic ingrowth and control groups. This effect was maximum at 3 microM guanosine-5'-O-(3-thiotriphosphate). These results suggest that both hippocampal sympathetic ingrowth and cholinergic denervation affect the efficiency of coupling between the muscarinic cholinergic receptors and phosphoinositol turnover, with cholinergic denervation decreasing and hippocampal sympathetic ingrowth "normalizing" efficiency. Further, they suggest that the G-protein is the site at which hippocampal sympathetic ingrowth and cholinergic denervation mediate their effects. The results of these experiments are also discussed within the context of recent findings demonstrating G-protein abnormalities in Alzheimer's disease.

Adrenergic Fibers↗

Morphology of denervated human facial muscles.

17 biopsies of denervated facial muscles, the zygomatic, the orbicularis oris and the levator labii muscles, showed atrophic myofibers in most cases. There was loss of fiber typability when applying the NADH, the MAG and the alkaline ATPase reactions. The acid ATPase preparations allowed differentiation of myofibers into type I and type II without subtypes. Contrary to normal facial muscles that are richly endowed with motor endplates, no neuromuscular junctions were observed in denervated muscle fibers except one example which might have been obtained by false sampling from the marginal area of denervation or might be the result of partial reinnervation due to sprouting axons from the neighborhood. There was no correlation between the degree of muscle fiber atrophy and the duration of the paralysis. However, fibrosis corresponded to length of denervation. The presence of highly atrophic muscle fibers even 36 years after denervation indicates that the final aim of facial nerve surgery, namely the reinnervation of denervated facial musculature may still be achievable. However, endomysial and perimysial fibrosis may have a considerable impact on the final outcome of such facial nerve surgery. Unsatisfactory correlation between morphological and clinical as well as electromyographical findings in denervated facial muscles requires individual morphological study of each biopsy to assess the probable outcome of reconstructive facial nerve surgery. It therefore appears reasonable even in long-standing facial paralysis, to biopsy denervated facial muscles before or during surgical reanastomosation of the facial nerve. This study provides hints that morphological examination of denervated facial muscles may supplement clinical, electrophysiological, and possibly biochemical diagnostic findings.

Adolescent↗

Modulation of drug effects by regional sympathetic denervation and supersensitivity.

BACKGROUND: Regional sympathetic denervation, such as that produced by a myocardial infarction, causes electrophysiological heterogeneity in the ventricles. The purpose of this study was to test the hypothesis that such denervation could cause drugs to exert heterogeneous myocardial effects. METHODS AND RESULTS: Sympathetic stimulation increases the amplitude of cesium chloride-induced early afterdepolarizations (EADs). The amplitude of these induced EADs was used to determine whether drug responses were different in innervated versus denervated areas of the heart. A canine model of sympathetic denervation was created at the cardiac apex by either transmural myocardial infarction (n = 19) or phenol application (n = 11). Cesium chloride (84 mg/kg) was infused while monophasic action potential recordings were simultaneously obtained from the base and apex of the left ventricle using an epicardial contact electrode. We found that control (innervated) dogs (n = 17) showed no difference in the EAD amplitude recorded from the apex compared with the base. In dogs with apical sympathetic denervation, the EAD amplitude was greater at the innervated base during ansae subclaviae stimulation than at the denervated apex (25.8 +/- 6.6% at base versus 18.8 +/- 6.7% at apex, p less than 0.001). However, during norepinephrine infusion, the EADs recorded from the denervated apex were greater than those recorded from the innervated base (23.3 +/- 7.6% at apex versus 20.6 +/- 6.0% at base, p less than 0.02) due to denervation supersensitivity. CONCLUSIONS: These data show that regional myocardial denervation creates autonomic and electrophysiological heterogeneity and the substrate for heterogeneous drug actions. This drug-induced electrophysiological heterogeneity may be another mechanism for proarrhythmia.

Action Potentials↗

Effects of delayed re-innervation on the expression of c-erbB receptors by chronically denervated rat Schwann cells in vivo.

We propose that chronically denervated Schwann cells may be less able to respond to axonal signals than their acutely denervated counterparts, and that this lack of sensitivity may be one reason why axons fail to regenerate into chronically denervated nerve stumps. To test this proposal we have used in situ hybridization, and quantitative and qualitative immunohistochemistry to compare the expression of c-erbB2 and c-erbB4 receptors in Schwann cells denervated for up to 6 months in vivo, with that seen in Schwann cells denervated for similar periods of time but then exposed to regenerating axons. The results were correlated with the extent of axonal regeneration in each experimental group as assessed from transverse sections which had been double-immunolabelled using anti S-100 and anti-beta tubulin III antibodies. Since c-erbBs are receptors for neuronally derived neuregulins we probed the appropriate axotomised DRG neurons for expression of GGF2 mRNA. When the denervated distal stumps were anastomosed to acutely transected proximal stumps, GGF expression in DRGs increased transiently during the first week: we assume that secreted GGF2 derived from regrowing axon sprouts would have been available to Schwann cells in all distal stumps. Endoneurial cell proliferation (predominantly Schwann cell proliferation); levels of expression of c-erbB receptors by Schwann cells, and the degree to which axons regenerated into the distal stumps all decreased as the period of prior denervation increased: the longer the time of denervation, the lower the expression of c-erbBs in Schwann cells, and the smaller the percentage of bands of Bungner which were re-innervated.

Animals↗

Long-term retention of regenerative capability after denervation of skeletal muscle, and dependency of late differentiation on innervation.

The present study examines the influence of denervation on the regenerative ability of skeletal muscle in rats. Muscle denervation was achieved by transecting and ligating the cut ends of the sciatic nerve. Four to 48 weeks after denervation, the extensor digitorum longus (EDL) muscle was autotransplanted to induce muscle regeneration. The transplanted EDL muscles were examined at 1-12 weeks. Normal (i.e., no prior denervation) EDL muscle autotransplants were also examined for comparison. Denervation resulted in progressive atrophy of muscle, marked by a reduction in the size of myofibers and an increase in endomysialperimysial connective tissue. In spite of these alterations, typical events of muscle regeneration were invariably observed after transplantation. Initial myofiber degeneration and subsequent regeneration of myotubes occurred in a manner similar to normal muscle transplants. However, only a partial maturation of myotubes was observed in denervated muscles. These results show that extended denervation does not abolish the capability for muscle regeneration. The precursor myosatellite cells, proposed to be responsible for muscle regeneration, retain their regenerative potential after denervation. It is concluded, however, that the presence of intact innervation is crucial for the terminal differentiation and maturation of regenerating muscle.

Animals↗

Satellite cells and myonuclei in long-term denervated rat muscles.

BACKGROUND: The percentage of satellite cells rapidly decreases in aneurally regenerating soleus muscles of rat. Also denervation of intact muscles causes fiber loss and regeneration, but the fate of satellite cells is unknown; myonuclei have been suggested to undergo changes resembling those in apoptotic cells. METHODS: Rat soleus and extensor digitorum longus (EDL) muscles were denervated at birth or at age 5 weeks and investigated after periods of up to 38 weeks. At least 400 myonuclei in each muscle were assessed by electron microscopy, and satellite cell nuclei were counted. In situ nick translation and tailing were performed after 30 weeks denervation in order to demonstrate DNA breaks associated with apoptosis. RESULTS: Myotubes indicating regeneration were prominent in the adult denervated soleus and deep layers of EDL muscles after 7 weeks and in the superficial parts of EDL muscle after 16 weeks. The percentage of satellite cell nuclei slowly decreased to less than one fifth of normal after 20-30 weeks. Almost all satellite cells had vanished 10 weeks after neonatal denervation. Degenerating myonuclei in adult, but not in neonatally denervated muscles, remotely resembled apoptotic nuclei of lymphocytes, but no evidence of DNA breaks was found. CONCLUSION: Denervation of rat skeletal muscles causes, in addition to fiber atrophy, loss of fibers with subsequent regeneration. Proliferation of satellite cells under aneural conditions may lead to exhaustion of the satellite cell pool. This process is more rapid in growing than in adult muscles. Myonuclei in denervated muscles do not show DNA breaks which can be demonstrated by in situ nick translation.

Age Factors↗

Neuromuscular relationships in a muscle having segregated motor endplate zones. II. The response to partial denervation.

The cranial belly of the anterior gracilis muscle of the rat has two discrete motor endplate zones. A proximal zone is innervated by short branches of the obturator nerve, and a distal zone is innervated by (usually) two longer branches. Each muscle fiber is innervated at a single motor endplate although a substantial number lie within both endplate zones. In addition, motor units are divided between the two zones. In order to dissociate the role of the denervated endplate from that of the denervated muscle fiber in the promotion of motoneuron sprouting, the distal endplate zone in this model was denervated and the response at the proximal zone was studied. Comparisons were made with partial denervation of the muscle by division of the L4 ventral ramus and with partial denervation of the distal endplate zone. Denervation of the distal endplate zone produced profuse terminal sprouting at the proximal zone whereas division of L4 predominantly produced nodal sprouting at both zones. Partial denervation of the distal zone resulted in nodal sprouts in that zone and again mainly terminal sprouts at the proximal zone. The repeated association of terminal sprouting with division of the motor axons supplying the distal zone together with the knowledge that motor units are distributed between the two zones led to the conclusion that the terminal sprouting was stimulated by the reduction in size of motor units rather than by the presence of denervated muscle fibers in the vicinity of the endplates.

Animals↗

Denervated skeletal muscle stimulates migration of Schwann cells from the distal stump of transected peripheral nerve: an in vivo study.

We have tested the stimulation of Schwann cell migration from the distal stump of a 1 week transected sciatic nerve of adult rats by denervated skeletal muscle. Migrating Schwann cells were distinguished by the presence of non-specific cholinesterase (nChE) activity and glial fibrillary acidic protein (GFAP) at a distance of about 6 mm among denervated muscle fibres 4 weeks after insertion of the distal stump. In addition, the distal stump was introduced into the open end of a silicone chamber packed with artificial fibrin sponge (Gelaspon) soaked in homogenate from intact or denervated muscles. A larger amount of migrated Schwann cells was observed in the chambers filled with homogenate from denervated muscles. An alteration in the amounts of Schwann cells migrating into the silicone chambers observed after histochemical staining (nChE or GFAP) was supported by biochemical measurements of the nChE activity. The biochemical assessment of the nChE activity revealed the increased amounts of migrated Schwann cells in proportion to the protein contents of homogenates from the denervated muscles. In addition, heating of homogenate from the denervated muscles resulted in a diminution of Schwann cell migration. Bromodeoxyuridine incorporation did not show an increased proliferation of Schwann cells inside the chambers following application of homogenate from the denervated muscles in comparison with the homogenate from the innervated muscles. Our results suggest a stimulation of Schwann cell migration from the distal stump of the transected sciatic nerve by soluble factor(s) produced by denervated skeletal muscles.

Animals↗

Expression of mRNA for plasminogen activators and protease nexin-1 in innervated and denervated mouse skeletal muscle.

Plasminogen activators (urokinase-type, u-PA and tissue-type, t-PA) are serine proteases that have been suggested to play important roles in synaptic remodeling. The enzymatic activity of u-PA in particular has previously been shown to increase dramatically after denervation of skeletal muscle. Using (32)P-labeled riboprobes and Northern blots the expression of mRNA for u-PA, t-PA and the inhibitor protease nexin-1 (PN-1) has been studied in innervated and 1-10-days denervated hind-limb muscle from mouse. Using RNA extracted from innervated and 6-days-denervated mouse hemidiaphragm muscles the expression of these mRNAs has also been investigated in synaptic and extrasynaptic muscle regions. For both u-PA and t-PA the observed autoradiographic signals were similar for RNA extracted from innervated and denervated leg muscles. The signals were also similar for RNA extracted from perisynaptic and extrasynaptic regions of hemidiaphragm muscle but u-PA signals were lower in denervated than in innervated hemidiaphragm. No such difference was observed for t-PA. PN-1 mRNA levels were also found to decrease after denervation in the hemidiaphragm but no substantial decrease was observed in denervated hind-limb muscles. No difference was observed between PN-1 expression in perisynaptic and extrasynaptic regions. The effect of denervation on PA enzymatic activity in skeletal muscle is therefore likely to be mediated at some post-transcriptional level.

Amyloid beta-Protein Precursor↗

The effect of acute denervation on the microcirculation of skeletal muscle: rat cremaster model.

Although tissue is denervated during replantation of a severed part, tissue transfer, or muscle transplantation, there are few studies concerning the effects of acute denervation on muscle microcirculation. We have described a surgical procedure that totally denervates the rat cremaster muscle. Histological examination of the denervated tissue has given convincing evidence of nerve degeneration and skeletal muscle atrophy, accompanied by electrophysiological evidence of total denervation. The diameters of each component of the microcirculation were measured before and after denervation. Arterioles and arteries ranging in size from 10 to 70 microns in diameter were found to increase significantly in size immediately after acute denervation. Larger arteries and veins did not undergo significant diametrical increases. These findings suggest that total acute denervation significantly increases the diameter of small arteries and arterioles, thereby decreasing the resistance in the arterial bed and increasing blood flow. Since this phenomenon is of limited duration (20 min), it would appear to be ineffective in enhancing reperfusion and oxygenation at the time of reattachment of amputated parts or during vascularized tissue transfers, until methods of prolonging it for several hours or more are found.

Animals↗