Effects Of Chemical Denervation Research Articles

The effect of surgical and chemical denervation on ischaemia/reperfusion injury of skeletal muscle

Denervation decreases skeletal muscle's energy needs and alters its metabolism and circulation. Our study was designed in two stages to investigate the effects of surgical and chemical denervation on the ischaemia/reperfusion injury of skeletal muscle. Degenerative histological analysis, apoptosis scoring and tissue levels of malonyl-di-aldehyde (MDA) and nitric oxide end products (NOx) were studied to understand the extent of ischaemia/reperfusion injury of skeletal muscles. In the first stage, the effect of surgical denervation was investigated in four groups each containing six rats. The right biceps femoris muscle was used as the experimental muscle flap model. In the control group, only the ischaemia/reperfusion cycle was applied. Ischaemia was created by a tourniquet strictly wrapping the right lower extremity for 4h. After ischaemia, the tourniquet was cut, and the extremity was reperfused for another 4h. In the experimental groups, surgical denervation was applied 1 day, 7 days and 30 days before the ischaemia/reperfusion cycle. On the second stage, the effect of chemical denervation with botulinum toxin type-A (BoNT-A) was investigated in three groups, each containing six rats. In the experimental groups, BoNT-A was applied 1 day, 7 days and 30 days before the ischaemia/reperfusion cycle. The control group had the worst scores in all experiment parameters. Degenerative histology and apoptosis scores were significantly better in groups to which BoNT-A and SD were applied 1 or 7 days before the ischaemia/reperfusion cycle. Regarding tissue levels of MDA and NOx, the experiment groups had significantly better scores comparing to the control group. Both surgical and chemical denervation applied before muscle transfer increased muscle ischaemia tolerance. With similar experimental outcomes, denervation with BoNT-A can be preferred to surgical denervation because of its abundant clinical availability and it can be applied without any secondary surgery.

Effects of chemical denervation with 6-hydroxydopamine on myocardial responsiveness to isoproterenol in rabbits.

This study examined the hypothesis that chemical denervation with 6-hydroxydopamine (6-OHDA) would increase myocardial responsiveness to isoproterenol. Five days previously, 15 New Zealand white rabbits were given 60 mg/kg 6-OHDA intravenously. Fifteen control rabbits received vehicle. Hemodynamic, coronary blood flow (CBF), and cardiac output measurements were obtained before and during isoproterenol infusion (0.5 microgram/kg/min for 15 min). Norepinephrine tissue content, beta-adrenoceptor number (Bmax) and affinity (Kd), cyclic AMP content and cyclic AMP-phosphodiesterase (PDE) activity were measured in the subepicardium (EPI) and subendocardium (ENDO). Myocardial norepinephrine content was significantly decreased from 1263 +/- 292 (EPI) and 874 +/- 221 ng/g tissue (ENDO) in the control to 148 +/- 33 (EPI) and 90 +/- 45 ng/g tissue (ENDO) in the denervated group. There were no significant changes in cyclic AMP-PDE activity or Bmax and Kd of beta-adrenoceptors. Cyclic AMP content was similar at baseline, but controls had a significantly larger increase (123-155%) during isoproterenol infusion when compared to the denervated group (27-37%). The denervated animals showed a smaller increase in cardiac output during isoproterenol infusion (from 203 +/- 30 to 235 +/- 26 ml/min), when compared to the control animals (from 135 +/- 18 to 216 +/- 42 ml/min). Baseline CBF was significantly higher in the EPI but not ENDO of the denervated group (185 +/- 20 ml/100 g/min in EPI and 150 +/- 8 in ENDO) compared to the control group (108 +/- 13 in EPI and 133 +/- 17 in ENDO). The relative increase in CBF during isoproterenol infusion was smaller in the denervated group (44-45%) than the control group (107-109%). Isoproterenol infusions of 0.1 and 2.5 micrograms/kg/min showed similarly depressed coronary blood flow responses in denervated animals. Thus, the chemically denervated animals did not have beta-adrenoceptor upregulation, exhibited a lesser increase in cyclic AMP with isoproterenol, and had a reduced functional and coronary blood flow response to isoproterenol. This occurred without any significant change in beta-adrenoceptor number or affinity, or in cyclic AMP-phosphodiesterase activity, indicating there may be receptor uncoupling or other changes in the signal transduction pathway.

A study on the neuronal and non-neuronal stores of dopamine in rat and rabbit kidney

The present study has examined the effects of 6-hydroxydopamine (6-OHDA) alone and in combination with pargyline, desipramine and GBR 12909 and denervation as induced by occlusion of the renal artery (RAO) on the endogenous dopamine (DA) and noradrenaline (NA) contents in rat and rabbit renal tissues; the effects of chemical denervation on catecholamine levels in the left ventricle were also studied. In rat and rabbit renal medulla and rat renal cortex, 6-OHDA and pargyline plus 6-OHDA selectively reduced NA (85-92% reduction) without a parallel decrease in DA tissue content (19-27% reduction). This 6-OHDA- and pargyline plus 6-OHDA-insensitive DA pool was found to be resistant to denervation as induced by RAO. The NA-depleting effect of 6-OHDA in these renal areas was found to be prevented by the previous administration of desipramine, but not with that of GBR 12909. In the rabbit renal cortex, 6-OHDA selectively reduced NA (90% reduction) without a parallel depletion of DA (20% reduction); previous treatment with pargyline abolished this selectivity. Again, only desipramine, but not GBR 12909, was found to prevent the NA and DA depleting effect of 6-OHDA in the rabbit renal cortex. Denervation induced by RAO was also found to produce a parallel depletion of DA and NA tissue levels in this renal area. In the left ventricle, 6-OHDA alone or in combination with pargyline produced a parallel depletion of DA and NA tissue levels (79-88% reduction) in both species. These results provide evidence against the presence of independent dopaminergic neurones in rat and rabbit kidney and suggest that in rat and rabbit renal medulla and rat renal cortex most of DA is stored in a non-neuronal compartment; in rabbit renal cortex some of the DA appears to be located in noradrenergic neurones, in a store different from that which contains NA.

Effects of sympathetic denervation on liver fibroblasts: prevention by adenosine

1. The effect of chemical denervation with 6-hydroxydopamine (6-OHDA) upon portal tract fibroblasts of dogs and rabbits was studied. 2. Denervation led to a significant increase in the density of portal tract fibroblasts both in the dog and in the rabbit. 3. Mast cells, present in the dog but not in the rabbit liver, were also significantly increased by denervation. 4. Noradrenaline depletion induced by reserpine did not increase the density of fibroblasts in the liver portal spaces of the dog. Mast cell density, however, was actually decreased when compared with control. 5. Continuous i.v. infusions of adenosine (10 micrograms kg-1h-1) to dogs totally prevented the effects of 6-OHDA-induced denervation upon fibroblast and mast cell densities in the portal space connective tissue. 6. It is concluded that the sympathetic nervous system is exerting a repressive effect on liver fibroblasts, as was found to occur in various other mammalian tissues. Mast cells, which are known to be activated in various pathological processes of fibrosis, appear to share with fibroblasts a modulating effect from the sympathetic nervous system. 7. The results strongly support the hypothesis of adenosine being the sympathetic trophic factor involved in the control of fibroblasts in the connective tissue of dog liver. A similar role for adenosine had previously been found in the dog saphenous vein.

Effects of chemical denervation on β1- and β2-adreno-ceptors

Effects of chemical denervation by reserpine or 6-hydroxy-dopamine(6-OHDA) on β-adrenoceptor-adenylate cyclase system in rats were studied.The changes of 3H-dihydroalprenolol binding sites(Bmax) estimated by Scatchard analysis and c-AMP contents (basal(B) and isoproterenol stimulated(S) c-AMP) induced by the chemical denervations were monitored.Both reserpine(0.25mg/kg s.c. for 3days) and 6-OHDA(50mg/kg i.v. for 2days) reduced norepinephrine content(NE) in cardiac and lung tissues more than 90% (chemical denervation). The reserpine treatment produced a significant reduction of cardiac Bmax and basal c-AMP,while S to B ratio(S/B) was increased (supersensitivity).In lung tissue, however,reserpine did not influence Bmax, basal c-AMP and S/B significantly. The treatment of 6-OHDA also produced a significant decrease of Bmax and basal c-AMP in cardiac and lung tissues,but S/B was unchanged in both tissues.After a wash out period of 6-OHDA for 5days,NE and Bmax in lung returned to control value,while in cardiac tissue,they did not return completely.These findings suggest that the alteration of Bmax and basal c-AMP associated with the chemical denervations did not correlate with S/B.In reserpine treated lymphocytes, a significant increase in basal c-AMP and decrease of S/B were observed, while Bmax remained the control value.The reduction of S/B by reserpine was also observed in vitro.