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PubMed1998

Extrinsic denervation increases myenteric nitric oxide synthase-containing neurons and inhibitory neuromuscular transmission in guinea pig.

Enteric nerves can function normally without connections with the central nervous system. A contributing component of the functional autonomy exhibited by enteric nerves is their plasticity. In the present study, the number of nitric oxide synthase-immunoreactive (NOS-ir) myenteric neurons and inhibitory neuromuscular transmission were studied in extrinsically denervated ileal segments. Segments of ileum were extrinsically denervated by crushing the mesenteric blood vessels supplying a loop of ileum in anesthetized guinea pigs. Some unoperated animals were treated with capsaicin or 6-hydroxydopamine (6-OHDA) to disrupt primary afferent and sympathetic nerves, respectively. NOS-ir was localized using indirect immunofluorescence. Nerve-mediated relaxations of longitudinal muscle were studied in vitro using standard methods. At 7 weeks after extrinsic denervation there was a 93% increase in the number of NOS-ir myenteric neurons. The number of neurons containing detectable vasoactive intestinal peptide-ir neurons was not changed after extrinsic denervation. Neurogenic relaxations caused by 10, 20 and 50 Hz transmural stimulation were larger in extrinsically-denervated tissues compared to control tissues. The NOS antagonist, nitro-L-arginine (300 microM) inhibited neurogenic relaxations in control and extrinsically-denervated tissues. Capsaicin- but not 6-OHDA-treatment mimicked the effects of extrinsic denervation on NOS-ir and neurogenic relaxations of the longitudinal muscle. Active or passive properties of the longitudinal muscle were unaffected by extrinsic denervation. These data indicate that extrinsic denervation is associated with an increase in the number of myenteric neurons expressing detectable NOS-ir and potentiation of inhibitory transmission to longitudinal muscle. This effect is due to loss of extrinsic sensory nerves.

Animals↗
PubMed1999

Quantitative study of the effects of denervation and castration on the levator ani muscle of the rat.

The levator ani muscle (LA) of the rat is highly androgen-sensitive and, like all skeletal muscles, deteriorates structurally and functionally when denervated. In order to elucidate the interplay of neural and endocrine influences, the separate and combined effects of denervation and castration on myofiber cross-sectional area and nuclear populations were quantitatively studied. In one group of 4-month-old male rats (A), the LA was denervated. Another group (B) was surgically castrated and a third group (C) was both denervated and castrated. The control rats (D) remained both gonad- and nerve-intact. After two months, the LA was obtained for myofiber and nuclear enumeration, cross-sectional area and satellite cell frequency determination. In the denervated muscle of gonad-intact rats (Group A), myofiber cross-sectional area was markedly diminished (265.84+/-11.38 microm2; compared with controls [Group D]: 1519.98+/-79.41 microm2; P < 0.05). Satellite cell nuclei, as a percentage of total sublaminar nuclei (i.e., satellite cell ratio), increased significantly (4.26%, from a control value of 1.91%). Castration alone (Group B) resulted in pronounced myofiber atrophy (mean cross-sectional area: 754.03+/-89.63 microm2) but had no significant effect on satellite cell ratio (2.36%). The combination of castration and denervation (Group C) elicited the same degree of myofiber atrophy as denervation alone (Group A) but had no significant impact on satellite cell ratio. Instead, the nuclear count per myofiber declined to about a third of the control level (300.5+/-38.49 compared with 861.7+/-24.8; P < 0.05). The results indicate that the atrophic effects of denervation and castration on the LA are non-synergistic and mechanistically similar. They also show that the inability of satellite cells to respond mitotically to the withdrawal of neural input under disandrogenized conditions is a factor in the myonuclear depletion of the denervated muscle of castrated rats.

Anal Canal↗
PubMed2003

Responses to amputation of denervated ambystoma limbs containing aneurogenic limb grafts.

The developing neural tubes and associated neural crest cells were removed from stage 30 Ambystoma maculatum embryos to obtain larvae with aneurogenic forelimbs. Forelimbs were allowed to develop to late 3 digit or early 4 digit stages. Limbs amputated through the mid radius-ulna regenerated typically in the aneurogenic condition. Experiments were designed to test whether grafts of aneurogenic limb tissues would rescue denervated host limb stumps into a regeneration response. In Experiment 1, aneurogenic limbs were removed at the body wall and grafted under the dorsal skin of the distal end of amputated forelimbs of control, normally innervated limbs of locally collected Ambystoma maculatum or axolotl (Ambystoma mexicanum) larvae. In Experiment 1, at the time of grafting or 1, 2, 3, 4, 5, 7, or 8 days after grafting, aneurogenic limbs were amputated level with the original host stump. At 7 and 8 days, this amputation included removing the host blastema adjacent to the graft. The host limb was denervated either one day after grafting or on the day of graft amputation. These chimeric limbs only infrequently exhibited delayed blastema formation. Thus, not only did the graft not rescue the host, denervated limb, but the aneurogenic limb tissues themselves could not mount a regeneration response. In Experiment 2, the grafted aneurogenic limb was amputated through its mid-stylopodium at 3, 4, 5, 7, or 8 days after grafting. By 7 and 8 days after grafting, the host limb stump exhibited blastema formation even with the graft extending out from under the dorsal skin. The host limb was denervated at the time of graft amputation. When graft limbs of Experiment 2 were amputated and host limbs were denervated on days 3, 4, or 5, host regeneration did not progress and graft regeneration did not occur. But, when graft limbs were amputated on days 7 or 8 with concomitant denervation of the host limb, regeneration of the host continued and graft regeneration occurred. Thus, regeneration of the graft was correlated with acquisition of nerve-independence by the host limb blastema. In Experiment 3, aneurogenic limbs were grafted with minimal injury to the dorsal skin of neurogenic hosts. When neurogenic host limbs were denervated and the aneurogenic limbs were amputated through the radius/ulna, regeneration of the aneurogenic limb occurred if the neurogenic limb host was not amputated, but did not occur if the neurogenic limb host was amputated. Results of Experiment 3 indicate that the inhibition of aneurogenic graft limb regeneration on a denervated host limb is correlated with substantial injury to the host limb. In Experiment 4, aneurogenic forelimbs were amputated through the mid-radius ulna and pieces of either peripheral nerve, muscle, blood vessel, or cartilage were grafted into the distal limb stump or under the body skin immediately adjacent to the limb at the body wall. In most cases, peripheral nerve inhibited regeneration, blood vessel tissue sometimes inhibited, but other tissues had no effect on regeneration. Taken together, the results suggest: (1) Aneurogenic limb tissues do not produce the neurotrophic factor and do not need it for regeneration, and (2) there is a regeneration-inhibiting factor produced by the nerve-dependent limb stump/blastema after denervation that prevents regeneration of aneurogenic limbs.

Ambystoma↗
PubMed1981

Effect of denervation on cyclic nucleotide metabolism in different types of skeletal muscle of the rat.

Slow-twitch soleus and fast-twitch extensor digitorum longus muscles of the rat were denervated unilaterally by sciatic nerve section at mid-thigh level. Activities of adenylate cyclase, guanylate cyclase, low Km and high Km cyclic AMP phosphodiesterase, and cyclic GMP phosphodiesterase were compared on the same, freshly prepared homogenates of denervated and shamoperated contralateral muscles one, two, three, or five days after surgery. As an early consequence of denervation, cyclic AMP metabolism was differentially affected in these different types of skeletal muscle. The adenylate cyclase activity of soleus muscle increased significantly by the second day following denervation and continued to rise through the fifth day, while this enzyme did not increase in denervated extensor digitorum longus even by the fifth day. The high Km cyclic AMP phosphodiesterase was already increased by day one in the denervated soleus, but not until the fifth day in the denervated extensor digitorum longus. Parallel increases beginning the first day were observed for the low Km cyclic AMP phosphodiesterase in both muscles. Since the activity of cytosolic cyclic AMP-dependent protein kinase of soleus muscle was also increased two days following denervation, the changes in cyclic AMP synthetic and degradative enzymes apparently result in a rise in intracellular cyclic AMP concentration. Alterations of the cyclic GMP enzymes following denervation were similar in the soleus and extensor digitorum longus, but were delayed relative to the increases in activity in the cyclic AMP enzymes.

Animals↗
PubMed2000

Delayed rat facial nerve repair leads to accelerated and enhanced muscle reinnervation with reduced collateral axonal sprouting during a definite denervation period using a cross-anastomosis paradigm.

To establish the influence of prolonged denervation on the recovery of a motor nerve, the rat facial nerve was transected and denervated for 0 to 224 days. Then, the freshly transected hypoglossal nerve was sutured to the predegenerated facial nerve (hypoglossal-facial nerve anastomosis, HFA). Using this nerve cross-anastomosis paradigm we analyzed the nerve regeneration and muscle reinnervation 7 to 112 days post-suture operation (DPSO). After HRP injection into the whiskerpad 931+/-27 hypoglossal neurons were labeled at 112 DPSO after immediate HFA. Following 14 to 112 days denervation the number of labeled neurons increased to 138% (14 days delay), 154% (56 days), and 145% (112 days). In contrast, the reinnervation was poorer after 7 days denervation with the number of neurons increasing to 84%, and after long-term denervation of 224 days the number of neurons increased to 81%. The increase in amplitude of evoked electromyography wave after nerve suture correlated with the number of labeled neurons. After immediate HFA each regenerated motoneuron established on average 5.1 myelinated sprouts at 112 DPSO. The number of sprouts remained constant after delayed suture of 14 to 112 days, whereas the slower reinnervation after 7 or 224 days delay was accompanied by a massive sprouting of 9.1 or 8.1, respectively, sprouts per neuron. The muscles showed recovery after any denervation time. The muscle cross-sectional area continuously decreased with longer denervation time. This decrease was only significant after 224 days denervation (67% of the normal value). We conclude that motor nerve reconstruction achieves better functional results after a definite period of denervation when using a nerve cross-anastomosis paradigm.

Anastomosis, Surgical↗
PubMed1996

Changes in some troponin and insulin-like growth factor messenger ribonucleic acids in regenerating and denervated skeletal muscles.

To investigate the role of innervation and to determine if the process of muscle differentiation is preprogrammed, the expression of insulin-like growth factors (IGF-I and IGF-II), troponin I and troponin T mRNAs was studied in regenerating transplants of rat Extensor digitorum longus muscle in the presence and absence of nerve. The role of innervation was further investigated by denervating some adult fast (Gastrocnemius and Plantaris) and slow (Soleus) skeletal muscles. In normal adult skeletal muscles, IGF-I, IGF-II and developmental fast troponin T mRNA containing exon y, are undetectable or present at very low levels. Induction of all these mRNAs was observed in regenerating muscles in both the presence and absence of nerve as well as following denervation of adult fast and slow skeletal muscles. Their low level expression was maintained in adult denervated skeletal muscles but gradually suppressed in both innervated and noninnervated regenerating extensor digitorum longus muscle transplants after 2 months. Fast troponin T mRNA was synthesized in both innervated and noninnervated EDL transplants although the level of this transcript changed markedly in response to denervation of both adult fast and slow skeletal muscles. The fast troponin T mRNA containing exon 17 was also initially expressed in both regenerating muscles but its level was reduced with time in both transplants and in all adult denervated skeletal muscles. Fast and slow troponin I mRNAs were synthesised during EDL muscle regeneration in both the presence and absence of nerve but the slow troponin I expression was not maintained in noninnervated transplants. The level of fast troponin I mRNA decreased in denervated fast skeletal muscles but markedly increased in denervated Soleus. The level of slow troponin I mRNA was slightly increased in denervated fast skeletal muscles but considerably reduced in denervated Soleus.

Animals↗
PubMed1984

Caffeine contractures in denervated frog muscle.

Caffeine contracture tension, effect of caffeine on the resting membrane potential, and caffeine influx in normal and denervated frog sartorius muscle have been investigated. Peak caffeine contracture tension is increased after denervation at all caffeine concentrations. The percentage increases in tension are highest for lower caffeine concentrations. The caffeine concentration required for half maximum tension is decreased from about 3.6 mM in control muscles to 2.6 mM in denervated muscles. Caffeine at 3.5 mM produces a depolarization of about 6 mV in control muscles and 16mV in denervated muscles. The large contracture tensions observed in denervated muscles are not due to the greater depolarization produced by the drug in denervated muscles since innervated muscles depolarized to the same level by external K+ do not enhance caffeine contracture tension. Both control and denervated muscles are highly permeable to caffeine. The increases in sarcoplasmic reticulum development ( Moscatello et al. 1965) and calcium content ( Picken and Kirby 1976) promoted by denervation may explain the larger tension elicited by caffeine in denervated muscles.

Animals↗
PubMed1985

Proximal tubular transport and urinary excretion of sodium after renal denervation in sodium depleted rats.

The effect of unilateral renal denervation on renal handling of water, sodium and potassium was studied with clearance and micropuncture techniques in sodium depleted anaesthetized rats in the nondiuretic state. In clearance experiments renal denervation resulted in a +140 and +320% increase in urine flow and potassium excretion, but sodium excretion of innervated (I) and denervated (D) kidneys was similar (I: 12.0 +/- 2.0, D: 14.0 +/- 3.6 nM . min-1 . g-1; NS). However, upon the loop diuretic furosemide (1 mg . kg-1), a marked denervation natriuresis was observed (I: 2.8 +/- 0.9, D: 5.9 +/- 1.0 microM . min-1; P less than 0.05) and denervation diuresis and kaliuresis persisted, too (+95 and +60%, respectively). Micropuncture results revealed that fractional reabsorption of filtrate to late proximal puncture site was depressed by renal denervation from 62 to 49% while no change in time control rats was seen (64 +/- 2 vs. 64 +/- 1%; NS). In micropuncture experiments besides augmented urine flow (+82%) from D kidneys also a small denervation natriuresis was present (I: 21.6 +/- 6.4, D: 29.2 +/- 7.0 nM . min-1; P less than 0.05). It is concluded that the lack or marked attenuation of denervation natriuresis in sodium depleted rats were the result of an almost complete compensatory distal reabsorption of the excess sodium (but not of water and potassium) leaving the proximal tubule after denervation. The distal adaptive response can be overcome by furosemide.

Animals↗
PubMed2006

Basal and hyperaemic myocardial blood flow in regionally denervated canine hearts: an in vivo study with positron emission tomography.

PURPOSE: Positron emission tomography (PET) studies in patients with diabetic autonomic neuropathy (DAN) have demonstrated the impact of this disease on cardiac sympathetic innervation and myocardial blood flow (MBF). To investigate the effects of selective partial sympathetic denervation of the left ventricle (LV) on baseline and hyperaemic MBF, we measured myocardial presynaptic catecholamine re-uptake (uptake-1), beta-adrenoceptor (beta-AR) density and MBF non-invasively by means of PET in a canine model of regional sympathetic denervation. METHODS: In 11 anaesthetised dogs, the sympathetic nerves of the free wall and septum of the LV were removed by means of dissection and phenol painting. Three weeks later, the animals were studied with PET. MBF was measured at baseline and following i.v. adenosine (140 microg kg(-1) min(-1)) and dobutamine (20 microg kg(-1) min(-1)) using(15)O-labelled water. Sympathetic denervation was confirmed by an 80+/-12% decrease in the volume of distribution (V(d)) of [(11)C]hydroxyephedrine (HED) compared with innervated regions. Myocardial beta-AR density was measured using [(11)C]CGP12177. RESULTS: Innervated and denervated regions showed no differences in MBF at baseline and during adenosine or dobutamine. [(11)C]HED V(d)was inversely correlated with MBF in both regions at baseline, and the correlation was lost during hyperaemia in denervated regions. However, for any given value of MBF, [(11)C]HED V(d)was significantly lower in the denervated regions. beta-AR density was comparable in denervated and innervated regions (17.9+/-4.2 vs 18.4+/-3.3 pmol g(-1); p=NS). CONCLUSION: In this experimental model, selective, regional sympathetic denervation of the LV, which results in a profound reduction in [(11)C]HED V(d), did not affect baseline or hyperaemic MBF. In addition, we demonstrated that, under baseline conditions, there was a significant inverse correlation between [(11)C]HED V(d)and MBF in both denervated and innervated regions.

Animals↗
PubMed1994

Influence of aortic baroreceptor denervation on adenosine receptor-mediated relaxation of isolated rat aorta.

The effect of aortic baroreceptor denervation on the vasorelaxant activity of the adenosine analogue, 5'-N-ethylcarboxamidoadenosine (NECA) was evaluated in the isolated thoracic aortic rings from rats. The responses were evaluated at 3 h after baroreceptor denervation when the blood pressure was significantly higher than that of control (149 +/- 3 vs. 112 +/- 2 mmHg) and at 48 h after aortic baroreceptor denervation when blood pressure returned to control level. Sham operation had no effect on blood pressure at either time interval. A concentration-dependent relaxation of rat aorta elicited by NECA was observed in all groups. However, the responsiveness to NECA was reduced in aortic baroreceptor-denervated rats. The nitric oxide (NO) synthase inhibitor, L-monomethyl-L-arginine (30 microM) shifted the dose-response curve for NECA to the right in all groups suggesting that the vascular response to NECA is partially mediated through the release of NO. Removal of the endothelium abolished the differences in the response to NECA in sham and aortic baroreceptor-denervated rats suggesting that the decrease in the responsiveness of aortic smooth muscle to NECA is dependent on the release of NO. Vasorelaxant responses to acetylcholine were not altered by aortic baroreceptor denervation. The ability of aortic baroreceptor denervation to attenuate vasorelaxant responses to NECA but not to acetylcholine indicated the possibility of functional changes involving adenosine receptor-mediated relaxation in endothelium rather than structural changes due to aortic baroreceptor denervation. These findings suggest that short-term elevation of blood pressure following aortic baroreceptor denervation modulates the endothelium-dependent release of NO mediated by adenosine receptor activation.

Acetylcholine↗
PubMed1992

Re-innervation of submucosal arterioles by myenteric neurones following extrinsic denervation.

We used a combination of selective lesions, immunohistochemistry and video monitoring of arteriolar diameter to determine the source of the changes in vasodilator innervation to guinea pig ileal submucosal arterioles which occur following removal of their extrinsic sympathetic and sensory nerve fibre input. A non-cholinergic neurogenic vasodilation appeared in arterioles in which extrinsic denervation was performed 50-90 days previously. The non-cholinergic innervation did not result from regrowth of extrinsic fibres because the neurogenic response was not altered by combining long-term denervation with capsaicin treatment or re-denervation 7 days prior to examination. However, non-cholinergic neurogenic vasodilations were not observed in arterioles which had been subjected to long-term denervation combined with a myectomy 7 days prior to examination. Immunohistochemical co-localization of SP and CGRP in these vessels confirmed previous findings that a prominent SP perivascular nerve plexus appeared after long-term denervation. Perivascular SP-containing fibres that appeared after long-term denervation were unaffected by capsaicin or re-denervation but were absent from preparations in which long-term denervation and myectomy were performed. These results demonstrate that myenteric neurones are the source of the non-cholinergic innervation which appears after extrinsic denervation and support our previous conclusion that SP is the neurotransmitter responsible for this non-cholinergic vasodilation in submucosal arterioles of the small intestine.

Animals↗
PubMed1996

The recovery of long-term denervated rat muscles after Marcaine treatment and grafting.

Disruption of the nerve supply results in the rapid loss of mass and contractile force in skeletal muscles. These losses are reversible to a high degree in short-term denervated muscles with grafting and nerve implantation. However, return is much poorer in long-term denervated muscles. This study examined the basis for the differences in the recovery of non-denervated and 7-month denervated rat extensor digitorum longus (EDL) muscles after grafting and nerve implantation. We found that the level of recovery is related to the ability of muscle fibers to degenerate and regenerate after grafting. Fibers within long-term denervated muscles do not degenerate and regenerate as well as those within muscles which are not denervated prior to grafting. The functional recovery of the denervated muscles is significantly improved when their fibers are induced to degenerate with the myotoxic anesthetic, Marcaine, Degeneration of these fibers is followed by massive regeneration. The finding that denervated muscles are capable of being restored to a significant level by inducing regeneration may be useful in the clinical treatment of denervated muscles.

Analysis of Variance↗
PubMed2004

Ventral cardiac denervation reduces the incidence of atrial fibrillation after coronary artery bypass grafting.

OBJECTIVES: Because the autonomic nervous system is an important determinant in the appearance of atrial fibrillation, we have assessed the role of ventral cardiac denervation for its prevention. METHODS: Patients undergoing low-risk coronary artery surgery were enrolled. No routine antiarrhythmic drugs were administered before or after the operation. Ventral cardiac denervation was performed in 207 patients, and 219 patients were used as control subjects. Denervation was performed before cardiopulmonary bypass. The groups were comparable regarding demographic, clinical, and operative variables. RESULTS: The additional time for the denervation was 5 +/- 2 minutes, and there were no associated complications. Postoperative atrial fibrillation was present in 15 (7%) patients undergoing ventral cardiac denervation (95% confidence interval, 4%-12%) and in 56 (27%) control subjects (95% confidence interval, 18%-35%). Patients submitted to ventral cardiac denervation had fewer and less severe episodes of atrial fibrillation, and no patient had atrial fibrillation after discharge. Ventral cardiac denervation was the most significant predictor of postoperative atrial fibrillation (odds ratio, 0.42; confidence interval, 0.23-0.78; P =.006). Age of greater than 65 years (odds ratio, 1.67; confidence interval, 0.96-2.9; P =.067) was a highly suggestive predictor. The analysis of the effect of ventral cardiac denervation correlated with the patient's age showed a more pronounced effect in patients younger than 70 years (odds ratio, 0.43; confidence interval, 0.22-0.86; P =.022) CONCLUSIONS: Ventral cardiac denervation is a fast and low-risk procedure. Its use significantly reduces the incidence and severity of atrial fibrillation after routine coronary artery bypass surgery. Patients younger than 70 years of age are expected to have a higher success rate than those older than 70 years.

Adrenergic beta-Antagonists↗
PubMed1989

Denervation supersensitivity of the rabbit urinary bladder to calcium ion.

We investigated in vitro the supersensitivity of denervated rabbit bladder to Ca2+. Seven days after denervation achieved by bilateral sacral rhizotomy, the capacity of the denervated bladder increased by 2.2 times as compared with the control (126.3 to 277.3 ml.), and wet weight also increased 4.3 times (3.6 to 15.3 gm.). After 30 minutes incubation in normal Krebs' solution the denervated bladder strips showed significantly increased amplitude of contractions to the cumulative acetylcholine addition than the control. After incubation in normal Krebs' solution for 30 minutes, muscle strips were washed three times with Ca-free Krebs' solution and incubated 30 minutes in this solution. Cumulative Ca2+ replenishment (0.5 to 10 mM) induced dose-dependent contractions of the detrusor muscle strips in Ca2+-free Krebs' solution, where the contractions were significantly stronger in the denervated detrusor muscle than in controls. Pretreatment with 10(-6) M verapamil (Ca-entry blocker) eliminated the enhanced Ca2+-induced contractions of the denervated detrusor strips, while 10(-6) M procaine (Ca-induced Ca releasing blocker) only partially inhibited them. After depolarizing the cell membrane with 40 mM KCl, the Ca2+-induced contractions of the control strips were markedly enhanced but those of the denervated strips were not. These results demonstrate the supersensitivity of the denervated detrusor muscle to Ca2+. We conclude that hyperpermeability of the cell membrane to Ca2+ influx through calcium channels is responsible for supersensitivity of the denervated detrusor muscle to Ca2+.

Acetylcholine↗
PubMed2001

Effects of denervation on Ca2+ channels in slow skeletal muscle fibers of the frog.

Effects of denervation on calcium channels in slow skeletal muscle fibers in the frog (Rana pipiens) were studied using the three-microelectrode voltage-clamp technique in intact fibers. Ca2+, Ba2+, and Sr2+ currents were all significantly reduced in amplitude during the first 2 weeks after denervation. After nerve section the selectivity sequence Ba congruent with Ca > Sr was changed to Ba > Sr > Ca and the values for relative ratio increased from 1.04 to 2.65 for Ba2+ and from 0.58 to 1.20 for Sr2+ (with respect to Ca2+). Barium current saturation was more obvious in denervated fibers than in non-denervated fibers. The values obtained with the Michaelis-Menten type expression, I = Imax/(1+Kd/[Ba]e) were Kd = 2.7 mM and Imax = 20 microA/cm2 in fibers 2 weeks after nerve section compared with the values Kd = 4.4 mM and Imax = 60 microA/cm2 obtained in non-denervated fibers. Additionally, the effects of two calcium channel blockers (cobalt and nifedipine) were greater by a factor of two in denervated fibers than in non-denervated fibers. Three weeks or so after nerve section, all the biophysical properties studied began to show a tendency to recover toward the values obtained in non-denervated muscles (controls). These results suggest that calcium channels are modified or that there is a change in the types of calcium channels present in frog slow skeletal muscle fibers after denervation.

Animals↗
PubMed2000

Effect of surgical denervation on the viability of inferior epigastric neurovenous flaps in the rat.

The purpose of this study was to examine how the inferior epigastric neurovenous flap in the rat reacts to surgical denervation. The survival of a denervated flap was compared with that of an innervated flap. A 2 x 2-cm flap was raised in 30 female Wistar rats assigned randomly to six groups of 10 rats each: group 1, innervated neurovenous flap; group 2, denervated neurovenous flap, acute model; group 3, denervated neurovenous flap, chronic model; group 4, innervated inferior epigastric island flap; group 5, denervated inferior epigastric island flap, acute model; and group 6, control, composite graft. Acute denervation produced a significant decrease in the survival of the inferior epigastric neurovenous flap (p < 0.05). The surviving area of the innervated flaps decreased from 94+/-14% (mean +/- standard deviation) to 16+/-34% by acute denervation. Chronic denervation was effective in decreasing flap necrosis in these flaps (survival, 99+/-5%). There were no differences between the average viable area of the standard inferior epigastric flap in the denervated and innervated groups.

Animals↗
PubMed1994

Renal denervation potentiates the natriuretic and diuretic effects of atrial natriuretic peptide in anaesthetized rabbits.

1. The role of the renal nerves in modulating the action of atrial natriuretic peptide (ANP) in the kidney was studied by comparing the responses to ANP in innervated and surgically denervated kidneys in anaesthetized rabbits. 2. A low dose of ANP (0.05 microgram/kg per min, i.v.) was used to minimize the confounding effects of systemic hypotension. 3. The natriuretic and diuretic responses to ANP were significantly greater in denervated kidneys than in kidneys with intact innervation. Sodium excretion from denervated kidneys rose by 7.49 +/- 3.11 mumol/min in response to ANP (approximately 55%, P < 0.05) compared to 0.84 +/- 0.59 mumol/min (approximately 28%, NS) in innervated kidneys. Urine flow increased markedly in denervated kidneys by 73.2 +/- 29.9 mumol/min (approximately 60%, P < 0.05) but not in innervated kidneys. 4. Fractional sodium excretion increased significantly in denervated kidneys in response to ANP (median 2.3% to median 3.0%, P < 0.05). 5. Renal blood flow, glomerular filtration rate (GFR) and glomerular capillary pressure were unchanged in response to ANP in either denervated or innervated kidneys. Pre-glomerular vascular resistance fell in denervated kidneys during ANP infusion. 6. The natriuresis and diuresis observed in the denervated kidneys, due to an increased fractional excretion of sodium without increases in GFR or glomerular capillary pressure, is consistent with effects of ANP on tubular reabsorption of sodium. 7. Thus, ANP produced a natriuresis and diuresis at a low dose in denervated but not in innervated kidneys. This indicates that reflex activation of renal nerves may antagonize the renal effects of ANP.

Animals↗
PubMed1976

The effect of catecholamines on the influx of calcium and the development of tension in denervated mouse diaphragm muscle.

1 The nature of the catecholamine-induced contracture of chronically denervated mouse diaphragm muscle has been investigated and compared with the contractural response evoked by acetylcholine. 2 The time course of onset of catecholamine-sensitivity in denervated diaphragm muscles was similar to the development of acetylcholine sensitivity. However, catecholamine contractures were absent in tissues denervated for periods longer than 90 days whereas acetylcholine-sensitivity was still evident several months after denervation. 3 The catecholamine-induced contracture of the denervated muscle was inhibited specifically by beta-receptor blocking drugs and was unaffected by alpha-receptor blocking drugs and cholinoceptor antagonists. 4 Catecholamine-induced contractures of denervated muscles, unlike contractures to acetylcholine, were dependent upon the presence of spontaneous fibrillation and the amplitude of spontaneous fibrillation was increased by catecholamines. Fibrillation was absent in the presence of tetrodotoxin (1 muM), 2,4-dinitrophenol (10 muM), potassium cyanide (10 muM), ouabain (100 muM), in lithium chloride Ringer solution and at low temperature. Under these conditions catecholamine-induced contractures, but not those to acetylcholine, were abolished. 5 Labelled calcium was found progressively to enter denervated muscle fibres and this entry of calcium was increased by catecholamines. It is suggested that this calcium entry may represent either an increased calcium permeability of denervated muscle fibres which is increased further by catecholamines or the presence of a calcium current that occurs during the fibrillatory potentials of denervated muscle.

Acetylcholine↗