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[Denervated myocardium detected by I-123 metaiodobenzylguanidine myocardial imaging following successful percutaneous transluminal coronary thrombolysis].

I-123 metaiodobenzylguanidine (MIBG) is taken up by sympathetic nerve endings. Thirteen patients with acute myocardial infarction, in whom reperfusion was achieved with percutaneous transluminal coronary thrombolysis (PTCR), MIBG and Tl-201 (Tl) images 14 days after PTCR which were simultaneously performed were studied. In the late stage, Tl myocardial stress test was also performed to detect ischemia. The extent of myocardial defect was estimated as percent defect. Wall motion was assessed by echocardiography. Ejection fraction (EF) was assessed in the chronic phase using left ventriculography. In nine of the 13 patients, the denerved myocardial regions having the MIBG defects were noted using a Tl uptake. A percent defect noted in MIBG images was 25 +/- 6% and was greater than those (6 +/- 6%,p less than 0.01) in Tl images. During the convalescent phase, the wall motion of the denerved region was restored (2, normal; 4, mild hypokinesis; 3, moderate hypokinesis) and in the chronic phase, EF was well preserved (61 +/- 14%). Ischemic regions noted in stress images coincided with denerved regions. In four patients without the denerved myocardium, EF was 46 +/- 3% (p less than 0.05) and wall motion of defect areas was akinetic. Both EF and myocardial viability were more preserved in cases with denerved region; i.e., PTCR was successfully performed in these cases. It was suggested that the denerved region was the area of severe ischemia during the acute phase and that it was salvaged by PTCR. The sympathetic nerve was damaged by severe ischemia, and depressed sympathetic function persisted long after the recovery of both myocardial perfusion and the wall motion.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

Cryosurgical denervation of the heart: acute and chronic effects.

A newly developed procedure for total cardiac denervation employing cryosurgical techniques is described. Thirty-three dogs underwent cryosurgical cardiac denervation. Twenty-seven survived the procedure and were divided into three groups. Completeness of denervation was evaluated by recording hemodynamic responses to sodium nitroprusside-induced hypotension, phenylephrine-induced hypertension, and direct cardiac autonomic nerve stimulations acutely (group I, n = 11) and 2 weeks after denervation (group II, n = 5). Serial drug infusion studies were performed during an 8-month period in group III animals (n = 11). Myocardial biopsies for catecholamine content were done in groups II and III. Both direct and reflex hemodynamic responses to autonomic neural stimulation were abolished in the acutely denervated hearts. Furthermore, at 2 weeks, direct neural stimulation was without effect, and myocardial catecholamine content was 95% depleted (p less than 0.001). Serial drug infusion studies revealed a changing spectrum of responses, suggesting the onset of reinnervation by 8 months following the procedure. Myocardial catecholamine content was 85% depleted at that time (p less than 0.001). Cryosurgical cardiac denervation is an effective technique offering the advantages of safety, simplicity, and completeness.

Animals↗

Angiotensin II receptors in adrenal gland, pituitary gland and brain of sino-aortic denervated rats.

Angiotensin II (ANG II) binding sites were quantified in individual adrenal and pituitary glands and brain nuclei of sino-aortic denervated (neurogenically hypertensive) and sham-operated rats by incubation of 16-microns tissue sections with 125I-[Sar1] Ang II, autoradiography, computerized microdensitometry and comparison with 125I-standards. In the anterior pituitary, the number of ANG II binding sites (Bmax) was increased in sino-aortic denervated rats, 764 +/- 39 versus 2025 +/- 340 fmol/mg protein in sham-operated versus sino-aortic denervated. In the adrenal medulla the Bmax was decreased in sino-aortic denervated rats, 3313 +/- 71 versus 2736 +/- 181 fmol/mg protein in sham-operated versus sino-aortic denervated. There were no significant changes in adrenal zona glomerulosa ANG II binding capacity. In the nucleus of the solitary tract the Bmax was decreased, from 1422 +/- 22 fmol/mg protein in sham-operated to 370 +/- 52 fmol/mg protein in sino-aortic denervated rats. These results indicate that changes in ANG II binding occur in peripheral tissues and brain of neurogenic hypertensive rats. Our findings suggest that both peripheral and central ANG II may be associated with the pathophysiology of neurogenic hypertension.

Adrenal Glands↗

Anatomy of the anterior interosseous innervation of the pronator quadratus: evaluation of structures at risk in the single dorsal incision wrist denervation technique.

PURPOSE: Patients with chronic wrist pain often are treated with wrist denervation, which typically involves transecting both the anterior interosseous nerve (AIN) and the posterior interosseous nerve. A single dorsal incision approach is an improvement over the more traditional multiple-incision technique. The purpose of our study was to describe the branches of the AIN to the pronator quadratus and evaluate the risk of denervation with the single dorsal incision technique. METHODS: Twelve fresh-frozen cadaver forearms were dissected. The branches of the AIN to the pronator quadratus were identified and the individual branch points were measured from the articular edge of the distal radius. Wrist denervation was then performed on each specimen through the single dorsal incision (as suggested by Berger). RESULTS: There were an average of 3 branches from the AIN to the pronator quadratus. All forearms had at least 1 branch to the pronator quadratus more proximal to the distal end of the dorsal skin incision; however, in only 2 of the forearms was the most proximal branch more than 2 cm proximal to the distal end of the dorsal skin incision. CONCLUSIONS: Wrist denervation through the recommended single dorsal incision poses a serious risk for completely denervating the pronator quadratus. Therefore the resection of the AIN must be performed close to the distal margin of the pronator quadratus.

Denervation↗

Transcutaneous neuromuscular electrical stimulation effect on the degree of microvascular perfusion in autonomically denervated rat skeletal muscle.

OBJECTIVE: To determine the effect of transcutaneous neuromuscular electrical stimulation (TNMES) on the degree of microvascular perfusion in autonomically denervated skeletal muscle. DESIGN: A completely randomized experimental design was used to compare the effects of TNMES on the degree of microvascular perfusion in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles from autonomically denervated rats (Ch-TES) to the degree of microvascular perfusion in the same muscles of untreated controls, rats receiving only TNMES (TES), and rats receiving only autonomic denervation (shams). INTERVENTION: All electrical stimulation treatments were delivered via carbon silicone surface electrodes, and evoked sustained tetanic contraction of the TA and EDL muscles. Autonomic denervation was achieved by the application of chlorisondamine. MAIN OUTCOME MEASURES: The degree of microvascular perfusion was determined for the deep (DTA) and superficial (STA) region of the TA muscle and the EDL muscle by calculating their perfused microvessel/muscle fiber (PV/F) ratio. RESULTS: The PV/F ratio in the DTA from Ch-TES animals was greater (p < or = .05) than that in the same muscle from control and sham animals. The PV/F ratios in the STA and EDL from Ch-TES animals were not significantly (p > .05) different from the PV/F ratio in the respective muscles of shams. CONCLUSIONS: The response of the microvasculature in autonomically denervated skeletal muscle to TNMES that evokes muscle contraction is variable, and (2) mechanisms other than autonomic regulation may be involved in this hyperemic response.

Analysis of Variance↗

The effect of duration of muscle denervation on functional recovery in the rat model.

The effect of long-term denervation on neuromuscular recovery was studied in a rat hind limb model. The posterior tibial nerve was transected and repaired immediately or after denervation periods of 2 weeks, or 1, 3, 6, 9, or 12 months. Six months following reconstruction excellent axonal regeneration was seen across all nerve repairs irrespective of periods of denervation. However, there was a precipitous and profound decrease in the recovery of both muscle mass and integrated motor function if the reconstruction was delayed for longer than 1 month. Rather than a progressive change proportional to the length of the denervation period, significant, more discrete changes occurred sometime after 1 month of denervation that precluded a full recovery of muscle mass. Integrated motor function quantified using walking track analysis was impaired even after immediate nerve repair.

Animals↗

Proteomic analysis of the atrophying rat soleus muscle following denervation.

A proteomic analysis was performed comparing normal rat soleus muscle to denervated soleus muscle at 0.5, 1, 2, 4, 6, 8 and 10 days post denervation. Muscle mass measurements demonstrated that the times of major mass changes occurred between 2 and 4 days post denervation. Proteomic analysis of the denervated soleus muscle during the atrophy process demonstrated statistically significant (at the p < 0.01 level) changes in 73 soleus proteins, including coordinated changes in select groups of proteins. Sequence analysis of ten differentially regulated proteins identified metabolic proteins, chaperone and contractile apparatus proteins. Together these data indicate that coordinated temporally regulated changes in the proteome occur during denervation-induced soleus muscle atrophy, including changes in muscle metabolism and contractile apparatus proteins.

Animals↗

Testosterone mediates satellite cell activation in denervated rat levator ani muscle.

Denervation stimulates quiescent satellite cells in skeletal muscle to reenter the cell cycle. In the androgen-sensitive rat levator ani muscle (LA), this mitotic response to loss of neural input fails to occur in castrated animals. To elucidate the role of androgens in denervation-induced satellite cell proliferation, the denervated LA of castrated rats (Group A) was compared with that of animals infixed with testosterone implants after castration (Group B). Mean myofiber cross-sectional areas (Group A: 362.95 microm(2) +/- 27.74; Group B: 403.13 microm(2) +/- 53.87) and linear nuclear densities (Group A: 74.07 mm(-1) +/- 17.58; Group B: 104.13 mm(-1) +/- 4.06) were similar (P > 0.05) in both groups. The androgen-deprived myofibers of Group A, however, had a significantly lower nuclear content (271.0 +/- 74.91 vs. 1,285.80 +/- 81.74 in Group B; P < 0.05) on account of their considerably shorter mean length (3.44 mm +/- 0.29 vs. 12.31 mm +/- 0.92 in Group B; P < 0.05). The proportional representation of satellite cells in hormone-replaced, denervated muscle was more than twice that in the untreated group (Group B: 5.15 +/- 0.83% vs. Group A: 2.28 +/- 0.23%; P < 0.05). In absolute terms, the satellite cell number in Group B was approximately an order of magnitude greater than in Group A (408.4 x 10(3) vs. 38.08 x 10(3)). The results confirm the absence of testosterone as the factor responsible for the inability of satellite cells in the LA of castrated rats to respond mitotically to the withdrawal of neural input after denervation.

Anal Canal↗

Regneration in free grafts of normal and denervated muscles in the rat: morphology and histochemistry.

Intact soleus and extensor digitorum longus muscles in the rat were freely grafted to the contralateral leg after either no preliminary treatment or 14 days prior denervation. Normal muscle grafts during the first week were characterized by a central zone of degenerating original muscle fibers (disappearing by 7-9 days) and a peripheral zone, containing regenerating muscle as well as small numbers of surviving original muscle fibers. A radial gradient of regeneration was establihed, with more mature muscle at the periphery and less mature muscle toward the center. Denervated grafts were characterized by rapid degeneration (within 2-3 days) of original muscle fibers in the central area, rapid appearance of regenerating muscle fibers (e.g. cross striations by 5 days) with uniform levels of differentiation throughout the graft and larger numbers of surviving original muscle fibers at the periphery. During the first week, stages of muscle differentiation in denervated grafts were attained 1-2 days earlier than comparable stages in normal grafts. Later stages of muscle differentiation were similar in both types of grafts. Histochemical studies revealed a loss of enzyme activity (phosphorylase, ATPase and SDH) in the center of early (2-4-day) normal and denervated grafts. Denervated grafts, however, possessed a thicker peripheral rim of enzymatically active surviving muscle fibers than normal grafts. In both types of grafts the old muscle fibers in the center were replaced by enzymatically active regenerating muscle fibers which stained uniformaly (ATPase) until 30 days. By 60 days a mixed fiber pattern had developed. Muscle spindles were found within the grafts.

Adenosine Triphosphatases↗

Age effects on cytochrome oxidase activities during denervation and recovery of three muscle fiber types.

The rat nasolabialis muscle is comprised of a mosaic of red, white, and intermediate muscle fiber types. Using computerized microdensitometry, cytochrome oxidase (COX) activity was quantitatively analyzed in each fiber type throughout the period of denervation and recovery in young adult (3-month) and middle-aged (15-month) male Sprague-Dawley rats. In animals of both age groups, the nasolabialis muscle on one side of the head was denervated by crushing the facial nerve. At specific days post crush (dpc) ranging from 2 days-2 months, animals were sacrificed and thick sections of normal and denervated muscles were incubated to demonstrate the activity of COX, a mitochondrial enzyme, which differentiates between the three fiber types. Enzyme activities in individual fibers were microdensitometrically analyzed using a digitizing image analyzer. Although a denervation-induced decreased followed by eventual recovery occurred in all fibers of each type, age-related differences were evident. For all types, younger fibers consistently showed decreased COX activity sooner than their older counterparts, and older fibers of all types consistently showed a greater decreased COX activity than the younger fibers. Denervation-induced de-differentiation of muscle fibers led to a more homogeneous population of fiber types in both age groups. Following recovery of function, the magnitude of the fiber enzyme activity change differed according to fiber type and to age, and was consistently smaller in older animals. The normal mosaic pattern of fiber type distribution and normal COX levels were restored 2 months after nerve lesion in both age groups.

Aging↗

Liver denervation affects hepatocyte mitochondrial fatty acid transport capacity.

The effect of liver denervation on the activity of hepatic carnitine palmitoyltransferase (CPT) system, which catalyses the transfer of long-chain fatty acids into the mitochondria, was studied in rats. Noradrenaline content in phenol-denervated liver (D) was reduced by 87%. CPT I and II activities (measured by radioassay after detergent separation of the enzymes) were decreased (p < 0.001) in D (2.6 +/- 0.1 and 0.68 +/- 0.2 nmol min(-1) mg(-1) protein, respectively) as compared with controls (4.7 +/- 0.3 and 2.5 +/- 0.2 nmol min(-1) mg(-1) protein, for CPT I and II, respectively). A less intense immunoreactive band for denervated liver CPT II was obtained after Western blotting. Concomitantly, long-chain fatty acid incorporation (p < 0.001), evaluated after administration of [14C]-oleate and total fat content (p < 0.001) were increased in D in relation to controls, while incorporation of exogenous [14C]-oleate into secreted VLDL, was decreased (p < 0.01). The effect of sympathetic denervation on CPT activity was different from that evoked by adrenodemedullation, which caused an augmentation of CPT activity (p < 0.01), when compared with the liver of intact rats. The effects of denervation and adrenodemedullation on the other parameters of lipid metabolism studied, were similar. The results strongly suggest a role of liver sympathetic innervation in the regulation of liver lipid metabolism.

Adrenal Medulla↗

Differential expression of nicotinic acetylcholine receptor genes in innervated and denervated chicken muscle.

We have studied the mRNAs encoding all four subunits of the acetylcholine receptor in 13-day embryonic, innervated and denervated chicken pectoral muscle. In all three states the transcript sizes of the alpha, beta-, gamma- and delta-subunit mRNAs were approximately 3.2, 2.8, 1.8 and 1.9 kb respectively. Denervation was found to result in a large increase in the steady-state levels of each mRNA compared with those in innervated muscle. This increase was 8- to 9-fold for the beta and delta subunits and approximately 12-fold for the alpha subunit. The evidence obtained shows a coordinate regulation of the acetylcholine receptor genes in response to denervation. Interestingly, no gamma-subunit transcript was detected in innervated muscle, while significant levels were detected in embryonic and denervated tissue. This evidence suggests that there exists in a non-mammalian muscle acetylcholine receptor an additional subunit, analogous to the bovine epsilon subunit, and shows that the extra-junctional receptor of adult denervated muscle is produced by the same set of mRNAs which produce the major form of the receptor in embryonic muscle.

Animals↗

Responses of denervated adult newt limb stumps to reinnervation and reinjury.

It is well known that denervated adults newt limbs do not regenerate. Not understood is why denervated newt limb stumps fail to initiate regeneration upon reinnervation. In an effort to define the regeneration limiting factors, we examined the histology of long-term denervated newt limb stumps and tested the effects of various kinds of reinjury. In 5-week denervated limb stumps there were present dedifferentiated cells, differentiated cartilage, and densely packed layered cells. The epidermis covering the limb tip resembled skin epidermis rather than wound epidermis. The kinds of reinjury that were successful in restoring the regeneration capabilities to 5-week denervated limb stumps included; reamputation (100%), a single razor incision (60%), and removal of the healed tissues from the distal limb tip (70%). The results of the study emphasize the importance of both injury and wound epidermis in initiating regeneration.

Amputation Stumps↗

Levels of cyclic GMP and cyclic AMP in regenerating forelimbs of adult newts following denervation.

The effect of short-term denervation (0, 12, 24, and 72 hours) on the levels of cyclic 3'5'-guanosine monophosphate (cGMP) and cyclic 3'5'-adenosine monophosphate (cAMP) in adult newt (Notophthalmus viridescens) forelimbs at 15, 22, and 35 days of regeneration was investigated. Regenerate blastema and stump cyclic nucleotide levels were compared with those of the contralateral intact forelimb and hindlimb, with levels in the normally regenerating blastema, and with levels measured in the forelimbs of intact, nonoperated animals. Variations in cyclic nucleotide levels occurred according to regeneration stage and tissue type. Changes in level were noted immediately upon denervation and subsequently at other sample times in all regenerate and control series. Parallel fluctuations occurred in regenerate stump and contralateral intact forelimbs. Our results from nonamputated denervated and sham-denervated animals indicate that short-term, denervation-associated cyclic nucleotide fluctuations cannot be attributed solely to the loss of innervation.

Animals↗

Effect of denervation on limb growth.

This study used Rana pipiens tadpoles to assess the effect of complete and partial sciatic denervation on tibial bone growth and foot growth. Complete sciatic denervation was performed in R. pipiens at Stages XIV, XVII, and XX and they were killed at Stages XVII, XX, and XXIV. Partial denervation consisted of peroneal or tibial nerve sectioning at Stages XVII and XX with killing at Stages XX and XXIV. Analysis of experimental animals and controls consisted of (a) quantitative axon counts, (b) tibial length, (c) midtibial cross-sectional area, (d) midtibial cortical thickness, (e) midtibial cartilage anlage cross-sectional area, (f) foot silhouette area, and (g) osteocyte number and osteocyte density. Both complete and partial denervation resulted in significant effects on bone and foot growth: (a) decreased bone length, (b) decreased cross-sectional bone area without cortical thinning, (c) increased cartilage anlage cross-sectional area, and (d) decreased foot size. This experiment demonstrated a trophic effect of nerve on bone growth and development and foot growth. The mechanism of this action is unknown but the data suggests a slowed rate of maturation in denervated bones. The possibility exists that defective peripheral nerve-limb tissue interactions may cause human deformities such as idiopathic clubfoot and idiopathic limb length discrepancy.

Animals↗

A method for testicular denervation in rats.

A successful method for microsurgical denervation of the testes in rats is described. Testes were unilaterally denervated in 15 animals. Thirteen untreated and two sham-operated rats served as controls. With the animal under ether anesthesia, the spermatic vessels on either side were exposed with the aid of microsurgical technique and an operating microscope. The area was then dyed with two to three drops of 1% Toluidine blue. With utmost precaution the nerves were separated from the vessels and resected. A biopsy specimen from the epididymal fat pad of each side was removed and assayed for norepinephrine content. The denervation procedure was considered successful if the norepinephrine content of the denervated fat pad was less than 11% of that of the contralateral fat pad. The denervation procedure was successful in 13 of 15 animals. No recognizable side effects from the use of Toluidine blue were observed.

Animals↗

Effect of muscle flap denervation on flow hemodynamics: a new model for chronic in vivo studies.

The purpose of this study was to evaluate microcirculatory dynamics following muscle flap denervation. A modification of standard cremaster muscle flap was used. Fifty male Sprague-Dawley rats were studied in two experimental groups of 25 rats each, as follows: Group I (control), after flap isolation, the neurovascular pedicle was left intact; group II (denervation), following muscle isolation at 1 cm segment of genitofemoral nerve was excised and denervated muscle was preserved in the medial border of rat hind limb. For chronic evaluation the cremaster was withdrawn from the leg and prepared for in vivo observations after days 1, 3, 7, and 14. The following measurements were taken: vessel diameters, red blood cell velocities, and number of perfused capillaries. In group II a 15% increase in arteriolar diameter was observed. Throughout the entire 14 day period denervated flaps presented 27% more perfused capillaries. Flap denervation proved to increase capillary perfusion significantly (P < 0.05). The cremaster muscle tube-flap model introduced in this study allows for chronic observation of the microcirculation.

Animals↗

Number of contractions to maintain mass and force of a denervated rat muscle.

Within 5 weeks, denervated extensor digitorum longus (EDL) muscles of rats lose 66% of mass, 91% of force, and 76% of fiber cross-sectional area (CSA). We previously determined the parameters of electrical stimulation for denervated rat EDL muscles to generate tetanic contractions sufficient to maintain mass and force close to control values. Using these parameters, we tested the hypothesis that a range exists for number of contractions per day, below and above which values for mass, maximum force, and fiber CSA are lower than values for innervated control muscles. For 5 weeks, denervated EDL muscles were stimulated to generate between 25 and 5000 contractions daily with contractions separated by constant intervals of rest, repeated 24 h per day. Force was not maintained with fewer than 200 or more than 800 contractions daily, whereas mass and fiber CSA were not maintained with fewer than 50 contractions daily. Protocols of stimulation that maintain muscle mass and force during prolonged periods of denervation may minimize problems clinically associated with denervation atrophy.

Animals↗