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Freeze-fracture studies of denervated and tenotomized rat muscle.

We studied the effects of denervation and tenotomy on the freeze-fracture ultrastructure of rat extensor digitorum longus muscle. The muscle plasma membrane was analyzed for the density of orthogonal arrays and caveolae. A period was found up to 30 days of age where innervation is required for the development and maintenance of orthogonal arrays. Denervation of older animals had no effect on the density of orthogonal arrays. The caveolar density increased after denervation at all ages. Tenotomy delayed the development of normal arrays, but had no significant effect on caveolar density. The results obtained for neonatally denervated rat muscles are similar to those seen in the muscles of patients with Duchenne muscular dystrophy.

Animals↗

Role of the adrenergic nerve terminal in digitalis-induced cardiac toxicity: a study of the effects of pharmacological and surgical denervation.

This study determined whether the protective action of bretylium against ouabain-induced ventricular arrhythmia in the cat is related to an action of bretylium on the adrenergic nerve terminal. Bretylium pretreatment (20 mg/kg, i.v.) administered 2 h prior to ouabain (2 micrograms/kg/min, i.v. until death) increased the dose of ouabain to produce premature ventricular contraction, ventricular tachycardia, and death from 77.2 +/- 5.2 to 107.7 +/- 6.7 micrograms/kg; from 84.9 +/- 5.2 to 113.9 +/- 7.1 micrograms/kg; and from 108.8 +/- 4.0 to 146.7 +/- 5.7 micrograms/kg, respectively (p less than 0.05). Surgical denervation 2 weeks prior to the experiment or 6-hydroxydopamine (6OH dopamine), 20 mg/kg, i.v., administered 3 or 14 days prior to the ouabain infusion did not protect against the arrhythmogenic effects of ouabain. When bretylium was administered to cats pretreated with 6OH dopamine 3 days prior to the ouabain infusion or to surgically denervated cats, the protective action against ouabain-induced arrhythmia did not develop. Since 6OH dopamine and surgical denervation prevented the action of bretylium on ouabain-induced ventricular arrhythmia, it appears that bretylium is acting on the adrenergic nerve terminal. Thus, agents like bretylium that act on the adrenergic nerve terminal, leaving it structurally intact but not functional, are effective against ouabain-induced ventricular arrhythmia while procedures which cause the degeneration of the adrenergic nerve terminal, such as 6OH dopamine and surgical denervation, are not. These observations indicate that for the protective effect of sympathectomy against ouabain-induced arrhythmia to develop, the adrenergic nerve terminal must be present, although not functional as far as adrenergic neurotransmission is concerned. Changes in the heart rate or blood pressure did not appear to be a factor in the protective effect of bretylium.

Animals↗

Central and peripheral alpha-adrenoceptor number and responsiveness after sinoaortic denervation in the rabbit.

The effects of bilateral sinoaortic denervation were examined in rabbits in vivo and in vitro. In the in vivo studies the effects of intravenous administration of the alpha-adrenoceptor agonists phenylephrine and guanabenz and the antagonists prazosin and phentolamine on mean arterial pressure, heart rate, and plasma catecholamine levels were investigated in intact sham-operated rabbits and after bilateral baroreceptor deafferentation. In in vitro studies the maximum number of prazosin and clonidine binding sites and their dissociation constants were investigated using radioligand binding techniques. Mean arterial pressure was labile and significantly elevated in the sinoaortic denervated rabbits. Heart rate and basal plasma noradrenaline were also raised, but plasma adrenaline and tissue noradrenaline levels were similar in intact and debuffered animals. alpha-Adrenoceptor antagonists were more effective at lowering mean arterial pressure in the sinoaortic-denervated animals. This was at least in part the result of a lack of compensatory changes in sympathetic activity and heart rate in these animals. Pressor responses to the alpha 1-adrenoceptor agonist and more markedly to the alpha 2-adrenoceptor selective agonist were increased after sinoaortic denervation. These changes could not be related to alteration in alpha 1- or alpha 2-receptor binding in either heart, spleen, or brain tissue as there was no change in number of binding sites or affinity.

Animals↗

Comparison between the effects of MDL 72567 and nifedipine on various cardiovascular parameters in conscious sinoaortic-denervated rats and sham-operated controls.

In this study the effects of a new calcium entry blocking agent, 2,6-dimethyl-3-methoxycarbonyl-4-(2-nitrophenyl)-5-(2-furoyl)-1, 4-dihydropyridine (MDL 72567), were compared with those of nifedipine on blood pressure, heart rate, ECG, and cardiac contractility indices in conscious sinoaortic baroreceptor-denervated (SA-denervated) rats and their sham-operated controls. In sham-operated rats, the calcium-entry blocking agents (0.1-2 mg/kg i.v.) produced equivalent falls in blood pressure. However, nifedipine caused a much greater reflex tachycardia which was accompanied by a negative inotropic effect, and with the highest dose (2 mg/kg), a prolongation of the PQ interval. MDL 72567 induced an increase in myocardial contractility. In SA-denervated rats, both drugs produced an enhanced fall in blood pressure accompanied by a negative inotropic effect. Nifedipine did not change heart rate in SA-denervated rats, whereas MDL 72567 caused bradycardia. Thus, in these experiments, MDL 72567 caused less reflex tachycardia for a given fall in blood pressure than nifedipine and was less likely to cause myocardial depression. These effects of MDL 72567 may represent valuable, clinically relevant advantages over nifedipine.

Animals↗

Arterial remodeling in chronic sinoaortic-denervated rats.

The spontaneous variation of blood pressure is defined as "blood pressure variability" (BPV). The chronic sinoaortic-denervated (SAD) rat is a model of high BPV without sustained hypertension. Little is known about vascular remodeling in this model. In the present study, we examined blood pressure, vascular remodeling, and aortic angiotensin II concentration in chronic SAD rats in separate experiments. In experiment 1, intra-arterial blood pressure was continuously recorded in conscious unrestrained rats. The 16-week SAD rats had a significant increase in BPV and no change in the mean level of blood pressure over a 24-h period. In experiment 2, we measured structural changes of seven kinds of arteries by histologic method and computer image analysis and functional changes of thoracic aortas by isolated artery preparation. Structural remodeling after 16-week sinoaortic denervation was characterized by increase in wall thickness, wall area, and ratio of wall thickness to internal diameter, with different changes in internal diameter and external diameter in different arteries, indicating that arterial structural remodeling expresses itself mainly as vascular growth. This vascular growth might be caused by medial smooth muscle cell growth and collagen accumulation. Aortic contraction induced by norepinephrine was potentiated, whereas aortic relaxation induced by acetylcholine was attenuated after sinoaortic denervation. In experiment 3, plasma and aortic angiotensin II concentrations were determined by radioimmunoassay. The former remained unchanged, whereas the latter was significantly increased in 10-week SAD rats. It is concluded that in rats chronic sinoaortic denervation can produce vascular remodeling that might be related to increased BPV and an activated tissue renin-angiotensin system.

Angiotensin II↗

Laparoscopic testicular denervation for chronic orchalgia.

PURPOSE: No specific cause is identified in most cases of chronic orchialgia. Nonsurgical therapies, including management at a chronic pain clinic, are generally recommended. Only when multiple conservative measures fail are patients offered surgical intervention, such as orchiectomy. We evaluate laparoscopic testicular denervation as an organ preserving and minimally invasive surgical alternative. MATERIALS AND METHODS: Since 1993, 9 patients with chronic orchialgia have undergone transperitoneal laparoscopic testicular denervation after nonsurgical modalities failed. Using 1, 10 mm. and 1 or 2, 5 mm. ports, the gonadal vessels were isolated circumferentially and divided cephalad to the vas deferens and its vasculature. Preoperative treatment modalities, morbidity and outcome were documented. A cord block provided temporary relief in all 9 patients. Analog scales were used to assess long-term pain relief (0 no pain to 100 worst pain) and activity levels (0 bedrest to 100 no restrictions). RESULTS: Average symptom duration before laparoscopic testicular denervation was 4.1 years. Of 9 patients 8 had undergone prior scrotal surgery. Failed nonsurgical modalities included anti-inflammatory drugs in 7 patients, antibiotics in 6, pain clinic consultations in 4 and antidepressant medications in 2. Mean pain score decreased from 69.4 (range 35 to 90) preoperatively to 30.6 at a mean followup of 25.1 months. Excluding the 2 cases that had no pain relief (less than 10-point reduction), average pain score decreased from 69 to 19 postoperatively (mean reduction 71%). Activity levels improved in all cases. There were no significant complications, including testis atrophy. One patient who had no pain relief underwent subsequent hydrocelectomy for pain, which also failed. CONCLUSIONS: Laparoscopic testicular denervation can provide significant long-term pain relief and appears to be a reasonable alternative in select cases with chronic orchialgia refractory to medical therapy. Larger series and prospective evaluations are necessary.

Adult↗

Microsurgical denervation of the spermatic cord as primary surgical treatment of chronic orchialgia.

PURPOSE: We evaluate the effectiveness of microsurgical denervation of the spermatic cord for treatment of chronic orchialgia. MATERIALS AND METHODS: Patients referred to our clinic diagnosed with chronic orchialgia are evaluated with a thorough medical and psychiatric history, physical examination and scrotal ultrasound when indicated. A total of 27 patients with chronic orchialgia refractory to nonsurgical management who had temporary pain relief after undergoing outpatient cord block were candidates for denervation. There were 6 patients who had bilateral pain, therefore, 33 testicular units were denervated. Followup ranged from 1 to 74 months (mean 20). RESULTS: Complete pain relief was noted in 25 (76%) testicular units, partial relief in 3 (9.1%) and no relief in the remaining 5 (15%), with a mean followup of 19, 24 and 10 months, respectively. There was no significant difference in outcome when evaluated by the etiology of orchialgia. CONCLUSIONS: When conservative treatment fails, microsurgical denervation of the spermatic cord should be considered first rate surgical therapy for patients with chronic orchialgia.

Adult↗

The effect of denervation on soft-tissue infection pathophysiology.

Pressure is the sine qua non in the etiology of pressure sores; however, ischemia, denervation, edema, and infection also have been implicated. The role of denervation in tissue infection was studied in an isolated in vivo ovine flap model. Twenty-six adult ewes, divided into three groups, had 29 island pedicle flaps raised on their buttocks. In group I, the cutaneous nerve remained intact, while group II had its nerve divided acutely. Group III had prolonged denervation, where the nerve was divided 7 days before flap elevation. All flaps received intradermal inoculations of 10(7) Staphylococcus aureus. Ninety-six hours later, quantitative bacteriology showed counts of 10(7), 10(7), and 10(9) colony-forming units (CFU) per gram of tissue in groups I, II, and III, respectively. Septic foci were larger in group III, and there was a significant increase in tissue edema between groups I and III. A 25-fold increase in bacterial counts seen in the prolonged denervation group may help explain why neurologically injured patients are more susceptible to infection and pressure ulcerations.

Abscess↗

Muscle flaps' triphasic microcirculatory response to sympathectomy and denervation.

Whether sympathectomy and somatic denervation in muscle flaps increased microcirculatory flow in the short or long term, thus producing an effect similar to the delay phenomenon, which increases survival in transferred skin flaps, was determined. The rat cremaster muscle flap model was used for in vivo microscopy. In the left cremasters of 30 Sprague-Dawley rats, the genitofemoral nerve was divided and the proximal vessels were stripped of their adventitia. The muscle was not elevated. In each rat, the contralateral cremaster served as the control. The rats were assigned to one of five groups: no delay before observation, a 24-hour delay, a 48-hour delay, a 7-day delay, or a 14-day delay. After the delay, red blood cell velocity, vessel diameters, number of functional capillaries, and leukocyte-endothelial interactions were measured. Microvessel response to topical vasoactive substances was measured. Immediately after denervation, red blood cell velocity increased transiently (71 percent; p = 0.006). Main arterioles dilated (20 percent; p = 0.02) at 24 hours, and capillary perfusion increased 36 percent (p = 0.001) at 2 weeks. The microvessels had hyperactive responses to all vasoactive agents 2 weeks after denervation. These findings indicate that proximal sympathectomy with somatic denervation leads to a triphasic, dynamic response in the peripheral microcirculation of the cremaster muscle flap. An initial acute hyperadrenergic phase was followed by a nonadrenergic phase, with significant vasodilatation, and a sensitized phase, with increased capillary perfusion and hyperresponsiveness to vasoactive substances. This study shows that with minimal access to the cremaster muscle flap neurovascular pedicle and without changing the blood supply to the flap, significant hemodynamic improvements can be made in the peripheral microcirculation.

Animals↗

Exocrine function of the heterotopic transplanted pancreas segment: influence of denervation in dogs.

We investigated the effect of denervation after heterotopic segmental pancreas autotransplantation on the exocrine function of the graft. The weight of the pancreas segment was determined, and secretory volume, bicarbonate output, and amylase activity were measured before and after i.v. infusion of secretin and cholecystokinin (CCK)-8. The studies were performed in untreated normal dogs, at 2 months postoperatively in partially pancreatectomized dogs with an innervated segment left in situ, and in totally pancreatectomized recipients of denervated heterotopic autotransplanted segments (approximately 30% of whole pancreas). The weight of the pancreas segment was similar in innervated and denervated dogs. Basal pancreatic secretory volume, bicarbonate output, and amylase activity were largely independent of cholinergic control. The secretory volume and bicarbonate output response to i.v. gut hormones (mainly secretin) were slightly modulated by cholinergic activity, whereas amylase response to gut hormones (mainly CCK-8) was quite independent of cholinergic control. We conclude that, after pancreas transplants, the effect of denervation on graft exocrine function is negligible--a finding that is reassuring if preserving of the exocrine tissue is important for optimal endocrine function of the graft.

Amylases↗

Meal-induced pancreatic polypeptide release in a validated pancreatic denervation model: a role for the distal pancreas?

In previous studies, postprandial pancreatic polypeptide (PP) release was diminished when pancreatic denervation was combined with distal pancreatectomy in animals without chronic fistulae. In contrast, postprandial PP release was reported to be unchanged when the pancreas was denervated without performing a distal pancreatectomy. These findings were unexpected given that the distal pancreas is a PP-poor region. To clarify this issue, we performed extrinsic pancreatic denervation, distal pancreatectomy, and insertion of chronic pancreatic fistulae in nine mongrel dogs. Insulin (0.5 U/kg) and meal-stimulated PP release were measured pre- and postoperatively. In addition, insulin- and meal-induced exocrine secretion was measured postoperatively. Preoperatively, insulin-induced hypoglycemia stimulated significant PP release (80,553 +/- 18,540 pg/min/ml). This response was completely abolished postoperatively (-1,669 +/- 5,054 pg/min/ml). Exocrine secretion did not increase above basal levels after administration of insulin in postoperative animals. These findings suggest adequate pancreatic denervation. Ingestion of a meal evoked significant PP response preoperatively (97,909 +/- 18,394 pg/min/ml). Postoperatively, the response was significantly blunted (17,231 +/- 6,407 pg/min/ml). This finding is in contrast to a previous report using a similar experimental preparation without distal pancreatic resection. We speculate that although the distal pancreas is PP-poor, it may play a role in the regulation of PP release from the PP-rich pancreatic head.

Animals↗

Effect of pancreatic denervation and atropine on the pancreatic response to secretin.

To study the influence of extrapancreatic nerves and intrapancreatic cholinergic activity on the pancreatic response to secretin, six dogs underwent extrapancreatic denervation and creation of pancreatic fistulae. A second group of six dogs had pancreatic fistulae created without pancreatic denervation. The pancreatic exocrine response to graded doses of secretin (16-500 ng/kg/h) was determined, both alone and during a background infusion of cholecystokinin-octapeptide (CCK8, 50 ng/kg/h). All studies were replicated during administration of atropine (10 micrograms/kg/h). Secretin-induced bicarbonate output was significantly inhibited by atropine in both the innervated and denervated groups. Combined secretin and CCK8 elicited a dose-dependent increase in bicarbonate output and a sustained increase in protein output in both groups, regardless of atropine. In addition, potentiation of secretin-induced bicarbonate output by CCK8 was observed despite both extrinsic pancreatic denervation and administration of atropine. We conclude that endogenous intrapancreatic cholinergic activity influences the pancreatic response to secretin. Potentiation of secretin-induced bicarbonate output by CCK, however, is not dependent on neural mediation.

Animals↗

The effect of pancreatic denervation and atropine on the cholecystokinin-induced pancreatic exocrine response.

To study the influence of extrapancreatic neural and cholinergic activity on the pancreatic response to cholecystokinin (CCK), six dogs underwent creation of Herrera pancreatic fistulas, placement of Thomas gastric cannulas, and distal pancreatectomies (innervated; INN). Six additional dogs were prepared similarly, with the addition of total extrinsic pancreatic denervation (denervated; DEN). The pancreatic protein and bicarbonate response to graded 12.5 to 200 ng/kg/h CCK doses was determined for INN and DEN animals both alone and with 10 micrograms/kg/h atropine infusion. The influence of extra-pancreatic neural and cholinergic activity on secretin's potentiation of the CCK-induced pancreatic response was then determined by repeating the studies with a 125 ng/kg/h secretin infusion. The latter results were compared to those predicted by summating the responses seen during separate 12.5-200 ng/kg/h CCK dose-response and 125 ng/kg/h secretin studies. Unstimulated protein output was diminished by atropine in INN animals (78 +/- 21 vs. 39 +/- 9 mg/15 min; p < 0.05) but not in DEN animals. Unstimulated bicarbonate outputs, integrated bicarbonate and protein outputs, and bicarbonate and protein dose-response curves were unaffected by denervation or atropine. Potentiation of CCK-induced bicarbonate output by secretin was also unaffected by atropine and denervation. We conclude that cholinergic elements are involved in unstimulated, but not CCK-induced, enzyme secretion. Further, potentiation of CCK-induced bicarbonate output by secretin does not depend on extrinsic neural or cholinergic elements.

Animals↗

Graft survival is improved by hepatic denervation before organ harvesting.

BACKGROUND: In a recent study, disturbances of hepatic microcirculation at harvesting caused by in situ organ manipulation dramatically reduced survival after a liver transplant. Because hepatic innervation is involved in the regulation of liver hemodynamics, the effect of denervation before harvesting was assessed here. METHODS: The livers were harvested from female Lewis rats (200-230 g) within 25 min. Briefly, after minimal dissection during the first 12 min, the livers were either manipulated gently or left alone for 13 min. Subsequently, an orthotopic liver transplant was performed after 1 hr of storage in cold UW solution. Some donors livers underwent microsurgical denervation before harvesting or rats were given hexamethonium (10 mg/kg, i.v.), a ganglionic blocking agent. RESULTS: In the nonmanipulated group, survival was 100% after the transplant; however, gentle manipulation decreased survival by about 50%. Furthermore, manipulation elevated serum transaminases and bilirubin 6- to 8-fold 8 hr after the transplant and caused necrosis of about 25% of hepatocytes. After organ harvesting, the rate of entry and exit of fluorescein dextran, a dye confined to the vascular space, was decreased 2- to 4-fold, and the maximal increase of surface fluorescence was blunted about 2-fold. Pimonidazole binding, which reflects tissue hypoxia, was increased 2-fold by manipulation. Denervation of the liver before organ harvesting or treatment with hexamethonium prevented the effects of organ manipulation on all parameters studied. CONCLUSION: These data indicate for the first time that hepatic denervation before organ harvesting prevents detrimental effects of brief, gentle manipulation of the liver during harvesting on survival after the transplant. This is consistent with the hypothesis that organ manipulation disturbs the hepatic microcirculation and causes hypoxia at harvesting using mechanisms dependent on innervation.

Animals↗

Does intradiscal electrothermal therapy denervate and repair experimentally induced posterolateral annular tears in an animal model?

STUDY DESIGN: The effects of intradiscal electrothermal therapy (IDET) on intervertebral discs in sheep were studied experimentally. OBJECTIVES: Posterolateral annular lesions were experimentally induced and allowed to mature for 12 weeks in the intervertebral discs of sheep. IDET was performed in an attempt to denervate and repair the annular lesion. The histologic and immunohistochemical effects of IDET were studied. SUMMARY OF BACKGROUND DATA: IDET continues to be used as a minimally invasive treatment for chronic discogenic low back pain, with success rates reported in up to 70% of cases. The mechanism of action by which IDET exerts its effect is poorly understood. Proposed mechanisms include the contraction of collagen and the coagulation of annular nociceptors. An ovine model was used firstly to induce a posterolateral annular lesion, secondly to assess the innervation of such a lesion, and thirdly to assess the effect of IDET on this innervation. MATERIALS AND METHODS: Posterolateral annular incisions were made in 40 lumbar discs of 20 sheep. Twelve weeks were allowed for each annular lesion to mature. IDET was then performed in the disc with the posterolateral annular tear and in another control level. IDET was performed using a modified intradiscal catheter (Spine-CATH; Oratec Interventions, Menlo Park, CA). Temperatures were recorded in the nucleus (TN) and the posterior annulus (TPA). The spines were harvested at predetermined intervals up to 18 months. Histologic sections of the discs were graded for disc morphology to assess degeneration and immunohistochemical staining to assess potential denervation. RESULTS: Vascular granulation tissue consistent with a healing response was observed in the posterior annular tear of all incised discs from 12 weeks. Protein gene product 9.5 (PGP 9.5) positive nerve fibers were clearly identified in the adjacent periannular tissue and the outer few lamellae of the posterior annulus. During the IDET procedure, the mean maximum TPA was 63.6C and the mean maximum TN was 67.C.At sacrifice, the number of nerve fibers identified in the posterior annular tear was the same for those specimens that had undergone IDET and those that had not. From 6 weeks after IDET, there was evidence of thermal necrosisin the inner annulus and adjacent nucleus but sparing the periphery of the disc. CONCLUSIONS: Vascular granulation tissue and posterior annular neo-innervation was observed in the experimentally induced posterolateral annular lesion. IDET delivered at 90C in the sheep consistently heated the posterior annulus and the nucleus to a temperature normally associated with coagulation of nociceptors and collagen contraction. IDET did not denervate the posterior annular lesion. Thermal necrosis was observed within the inner annulus and adjacent nucleus from 6 weeks after IDET. The reported benefits from IDET appear to be related to factors other than denervation and repair.

Animals↗

Characterization of matrix metalloproteinases in denervated muscle.

In a nerve crush model of denervation, we examined muscle matrix metalloproteinase (MMP) expression, localization and activity. In normal muscle, MMP mRNA levels were low, and immunohistochemically MMPs were distributed around the muscle fibre with MMPs-3, -7 and -9 also staining at the neuromuscular junction. Seven days after nerve crush, muscle MMP immunoreactivity, especially MMP-12 and MMP-14, became irregularly distributed. At 20 days reinnervation of the muscle was observed, and some restitution of the normal pattern of immunoreactivity was noted concomitant with a higher level of MMP mRNA expression. In situ zymography showed that MMP activity was very weak in normal muscle whereas it was increased up to 40 days following denervation. Our results suggest that MMPs in muscle are involved in the tissue changes following denervation. Further experiments are required to test the hypothesis that MMP inhibition may be beneficial in protecting muscle from excessive remodelling following denervation and therefore improve reinnervation.

Animals↗

Image analysis of blastema cell proliferation in denervated limb regenerates of the newt, Pleurodeles waltlii M.

When denervated at the medium bud stage, limb blastemas of the newt, Pleurodeles waltlii Michah, stop growing. In order to better understand the role of nerves in the cell cycle in blastemas, we studied the distribution of mesenchymal cells in the G0-1, G1, S, G2 and M phases 48 and 96 h after denervation. The cell-cycle phases were determined by examining Feulgen-stained nuclei using a SAMBA 200 (System for Analytical Microscopy in Biological Applications) cell image processor. The cell nuclei were automatically analyzed by calculating 18 parameters related to the densitometry and texture of chromatin, and the shape of each nucleus. Cell-cycle phases were classified according to the unsupervised recognition method using a SAMBA 200 system as proposed by Moustafa and Brugal for cell-kinetics analysis. The classification obtained was tested against the results of stepwise linear discriminant analysis performed according to the method of Giroud. Our results show that, in blastemas 96 h after denervation, the percentage of cells in the S, G2, and M phases decreases significantly, while the percentage of G1 and G0-1 cells increases (+ 51% for G1 cells; + 30% for G0-1 cells). Thus, it appears that denervation of medium-bud-stage limb blastemas promotes the lengthening of G1 and premature exiting of cells from the cycle into the G0-1 phase. These results show that nerves (i.e., neurotrophic factor) regulate cell kinetics during newt limb regeneration by maintaining blastema mesenchymal cells in the cell-cycle.

Animals↗

Effect of denervation on the distribution and developmental transition of phosphoglycerate mutase and creatine phosphokinase isozymes in rat muscles of different fiber-type composition.

Phosphoglycerate mutase (PGM) and creatine phosphokinase (CK) occur as three isozymes (types MM, MB and BB) in mammals and these exhibit similar transitions during skeletal muscle development. To study the influence of innervation on this transition and on the maintenance of the isozyme phenotype in mature muscle, we have determined the changes produced by sciatic neurectomy in neonatal and adult rat hindlimb muscles. In 40-day-old rats, denervation decreased both PGM and CK activity, the effect being more pronounced in the fast-twitch extensorum digitorum longus (EDL) and gastrocnemius muscles than in the slow-twitch soleus muscle. It also produced a progressive increase in the proportion of MB- and BB-PGM isozymes in EDL and gastrocnemius but not in soleus, and an increase of MB- and BB-CK isozymes in all three muscles. In 5-day-old rats, denervation prevented the developmental increase of PGM and CK activity in all three muscles. Denervation also prevented the normal decrease in the relative amounts of the MB and BB isozymes of both enzymes which occur during postnatal muscle development. These results can be explained by the different effects of denervation upon slow and fast muscles, and by the distinct distribution of PGM and CK isozymes in rat type I and II muscle fibers.

Animals↗