Total Denervation Research Articles

Correlation of intact sensibility and neuropathic pain-related behaviors in eight inbred and outbred rat strains and selection lines

In some rat strains, total hindpaw denervation triggers autotomy, a behavior of self mutilation presumably related to neuropathic pain. Partial sciatic ligation (PSL) in rats produces tactile allodynia and heat hyperalgesia but not autotomy. Our aims in this study were to examine: (1) whether sensibility of intact rats to noxious and non-noxious stimuli is strain-dependent; (2) whether sensibility of intact rats could predict levels of autotomy, or of allodynia and hyperalgesia in the PSL model; and (3) whether autotomy levels are correlated with levels of allodynia or hyperalgesia. Here we report that in two inbred rat strains (Lewis and Fisher 344), two outbred rat strains (Sabra and Sprague–Dawley) and four selection lines of rats (Genetically Epilepsy-Prone Rats, High Autotomy, Low Autotomy and Flinders Sensitive Line), tactile sensitivity and response duration to noxious heat of intact animals were strain-dependent. Levels of autotomy following hindpaw denervation and of allodynia and hyperalgesia in the PSL model were also strain-dependent. Thus, these traits are determined in part by genetic factors. Sensory sensibility of intact rats was not correlated with levels of autotomy following total denervation, or allodynia and hyperalgesia following partial denervation. We suggest that preoperative sensibility of intact rats is not a predictor of levels of neuropathic disorders following nerve injury. Likewise, no correlation was found between autotomy, allodynia and hyperalgesia, suggesting that neuropathic pain behaviors triggered by nerve injury of different etiologies are mediated by differing mechanisms.

Assessing baroreflex gain from spontaneous variability in conscious dogs: role of causality and respiration.

A double exogenous autoregressive (XXAR) causal parametric model was used to estimate the baroreflex gain (alpha(XXAR)) from spontaneous R-R interval and systolic arterial pressure (SAP) variabilities in conscious dogs. This model takes into account 1) effects of current and past SAP variations on the R-R interval (i.e., baroreflex-mediated influences), 2) specific perturbations affecting R-R interval independently of baroreflex circuit (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at frequencies slower than respiration), and 3) influences of respiration-related sources acting independently of baroreflex pathway (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at respiratory rate, including the effect of stimulation of low-pressure receptors). Under control conditions, alpha(XXAR) = 14.7 +/- 7.2 ms/mmHg. It decreases after nitroglycerine infusion and coronary artery occlusion, even though the decrease is significant only after nitroglycerine, and it is completely abolished by total arterial baroreceptor denervation. Moreover, alpha(XXAR) is comparable to or significantly smaller than (depending on the experimental condition) the baroreflex gains derived from sequence, power spectrum [at low frequency (LF) and high frequency (HF)], and cross-spectrum (at LF and HF) analyses and from less complex causal parametric models, thus demonstrating that simpler estimates may be biased by the contemporaneous presence of regulatory mechanisms other than baroreflex mechanisms.

Is the secretion of atrial natriuretic peptide in man under neural control?

Previous work has described short-term variation in the circulating plasma level of atrial natriuretic peptide (ANP), but the mechanism remains unknown. Our aim was to investigate the role of cardiac innervation in this variability. Blood samples were obtained from the right atrium via a pulmonary artery flotation catheter every 2 min over a 90 min period. Seven patients who underwent cardiac transplantation by the standard biatrial technique (partial innervation) and ten patients who underwent transplantation by the bicaval technique (total denervation) were studied. ANP levels were measured by radioimmunoassay. The median ANP levels were somewhat higher in the biatrial group compared to the bicaval group [470 (150-1095) vs. 216 (100-605) pg. ml(-1); median (range); P = ns], and both were much higher than normal levels in the pulmonary artery (40 (24, 56) pg ml(-1); median and interquartile range). In both transplant groups circulating plasma ANP levels showed considerable variability. The median number of 'peaks' and 'troughs', as counted by visual inspection, were not significantly different between the two groups. Computer analysis identified 12-16 and 6-15 'pulses' in the biatrial and bicaval group, respectively. Further analysis revealed that pulse amplitude, height and area were significantly higher in the biatrial compared to the bicaval group. It would appear that variability of circulating plasma levels of ANP is preserved despite complete or partial cardiac denervation, and so a neural mechanism does not appear to account for such variation.

Pancreatic secretory response to intraileal amino acids: studies in dogs with an in situ neurally isolated ileum.

Intraileal carbohydrates and lipids affect the pancreatic exocrine secretion, but the effect of intraileal amino acids and the role of the extrinsic nerves of the ileum as mediators of the pancreatic bicarbonate and enzyme output are unknown. Four dogs underwent total extrinsic denervation of the entire ileum. Thomas-like cannulas were placed into the stomach, duodenum (to collect pure pancreatic juice), and at the jejuno-ileal junction. Eight neurally intact control dogs received only the three fistulas. After recovery, in both sets of dogs, dose-response studies of the pancreatic secretory response to intraileal infusion with graded loads of tryptophan (0.12-10.0 mmol/h) were performed, given against an intravenous (iv) background of secretin (20.5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). On separate days, control experiments with intraileal infusion of 0.15 M NaCl were performed. In both sets of dogs, iv secretin plus cerulein significantly (p < 0.05) increased pancreatic bicarbonate and protein output above basal. Intraileal tryptophan caused a dose-dependent decrease in the pancreatic bicarbonate and protein response to secretin plus cerulein. In the dogs with denervated ileum, this inhibition was significantly stronger than in the intact animals. In both sets of dogs, the 225-min integrated bicarbonate (IBR) and protein response (IPR) to all loads of tryptophan were significantly lower than in control experiments. Both IBR and IPR were significantly lower in the denervated as compared with the intact animals. 1) Extrinsic denervation of the entire ileum is a valuable preparation to study the role of nerves in the control of pancreatic exocrine secretion; 2) both in the intact and denervated animals the amino acid tryptophan induces an "ileal brake" of the hormonally stimulated pancreatic bicarbonate and protein output; 3) the extrinsic nerves of the ileum are probably not the dominant mediators of the inhibitory action of intraileal tryptophan but rather counteract this effect.

Anatomical study of the neural ganglionated plexus in the canine right atrium: implications for selective denervation and electrophysiology of the sinoatrial node in dog.

The aim of the present study was to elucidate the topography and architecture of the intrinsic neural plexus (INP) in the canine right atrium because of its importance for selective denervation of the sinoatrial node (SAN). The morphology of the intrinsic INP was revealed by a histochemical method for acetylcholinesterase in whole hearts of 36 mongrel dogs and examined by stereoscopic, contact, and electron microscopes. At the hilum of the heart, nerves forming a right atrial INP were detected in five sites adjacent to the right superior pulmonary veins and superior vena cava (SVC). Nerves entered the epicardium and formed a INP, the ganglia of which, as a wide ganglionated field, were continuously distributed on the sides of the root of the SVC (RSVC). The epicardiac ganglia located on the RSVC were differentially involved in the innervation of the sinoatrial node, as revealed by epicardiac nerves emanating from its lower ganglia that proceed also into the atrial walls and right auricle. The INP on the RSVC (INP-RSVC) varied from animal to animal and in relation to the age of the animal. The INP-RSVC of juvenile dogs contained more small ganglia than that of adult animals. Generally, the canine INP-RSVC included 434+/-29 small, 17+/-4 medium-sized, and 3+/-1 large epicardiac ganglia that contained an estimated 44,700, 6,400, and 2,800 neurons, respectively. Therefore, the canine right atrium, including the SAN, may be innervated by more than 54,000 intracardiac neurons residing mostly in the INP-RSVC. In conclusion, the present study indicates that epicardiac ganglia that project to the SA-node are distributed more widely and are more abundant than was previously thought. Therefore, both selective and total denervation of the canine SAN should involve the whole region of the RSVC containing the INP-RSVC.

Activation of CNS Circuits Producing a Neurogenic Cystitis: Evidence for Centrally Induced Peripheral Inflammation

We present a model of neurogenic cystitis induced by viral infection of specific neuronal circuits of the rat CNS. Retrograde infection by pseudorabies virus (PRV) of neuronal populations neighboring those that innervate the bladder consistently led to a localized immune response in the CNS and bladder inflammation. Infection of bladder circuits themselves or of circuits distant from these rarely produced cystitis. Absence of virus in bladder and urine ruled out an infectious cystitis. Total denervation of the bladder, selective C-fiber deafferentation, or bladder sympathectomy prevented cystitis without affecting the CNS disease, indicating a neurogenic component to the inflammation. The integrity of central bladder-related circuits is necessary for the appearance of bladder inflammation, because only CNS lesions affecting bladder circuits, i.e., bilateral dorsolateral or ventrolateral funiculectomy, as well as bilateral lesions of Barrington's nucleus/locus coeruleus area, prevented bladder inflammation. The close proximity in the CNS of noninfected visceral circuits to infected somatic neurons would thus permit a bystander effect, leading to activation of the sensory and autonomic circuits innervating the bladder and resulting in a neurogenic inflammation localized to the bladder. The present study indicates that CNS dysfunction can bring about a peripheral inflammation.

Immunolocalization of nitric oxide synthases at the postsynaptic domain of human and rat neuromuscular junctions--light and electron microscopic studies.

Neuronal (n) and inducible (i) nitric oxide synthase (NOS) were immunolocalized at the postsynaptic domain of human and rat neuromuscular junctions (NMJs) by light and electron microscopy. We applied polyclonal and monoclonal antibodies for colocalization with three other synaptic proteins, utilizing double and triple fluorescence labeling, and gold and peroxidase for immunoelectron microscopy. By light microscopy, nNOS and iNOS colocalized with desmin and dystrophin, known postsynaptic components, but not with neurofilament protein, a presynaptic component. By electronmicroscopy, nNOS, but not iNOS, colocalized postsynaptically on the same structures as desmin; iNOS was also postsynaptic, but did not colocalize with desmin immunoreactivity. At the NMJs of Duchenne muscular dystrophy patients, both nNOS and iNOS were strongly immunoreactive. At the NMJs of a patient with myasthenia gravis, nNOS was weaker than in controls. Total denervation of rat sciatic nerve did not cause any decrease of nNOS or iNOS immunoreactivity 7 days thereafter. At 15 days after denervation, there was a gradual decrease of immunoreactivity, and immunoreactivity disappeared 30 days after denervation, corresponding to the ultrastructurally detectable disorganization of the postsynaptic region. This seems to be the first combined light and electron microscopic description of the postsynaptic localization of nNOS and iNOS at human and rat NMJs.

Diet can modify autotomy behavior in rats following peripheral neurectomy

Partial sciatic nerve ligation in rats (PSL) produces neuropathic pain disorders [Seltzer, Z., Dubner, R. and Shir, Y., Pain, 43 (1990) 245–250]. Recently we reported that diet markedly affected the levels of these disorders. Here we questioned whether diet also affects neuropathic pain-related behavior in another model, produced by total denervation of the hindpaw following peripheral sciatic and saphenous neurectomy. Sabra rats and HA line rats were fed for 2–3 weeks preoperatively and up to 58 days postoperatively (PO) with one of five different diet formulas. We found that the autotomy behavior differed significantly between the diet groups. Surprisingly, in some diets the effects on autotomy and PSL models were different and even contrasting. Modulation of diet in humans may emerge as a novel therapy of neuropathic pain.

Temporary loss of cardiac autonomic innervation after the maze procedure

Blunted sinus node response to exercise has been reported after the maze operation. We suggested the autonomic vegetative function of the heart to be disturbed after the maze procedure. 17 patients, mean age 63 +/- 15 years, with chronic atrial fibrillation for 49 +/- 46 months (range 5-65) underwent the maze procedure during mitral valve surgery. Bicycle stress test, 24-h electrocardiography and heart rate variability were analysed in 11 patients after three and in six after 14 +/- 3 months. Spectral analysis within two frequency bands, vector analysis of the main circular resultant and influence of orthostasis and Valsalva manoeuvre on different R-R intervals were calculated. One patient died from a perioperative ischaemic stroke. At follow-up, all patients were in sinus rhythm. Heart rate reached 84 +/- 14%, the mean circular resultant was 60 +/- 48%, the ratio of the longest to the shortest R-R interval during the Valsalva manoeuvre was 92 +/- 8% and the ratio of maximal to minimal R-R interval after orthostasis was 98 +/- 4% of the age-adjusted normal value. Maximal workload was 116 +/- 31 watts. All patients had abnormal heart rate variability. Heart rate variability was significantly more blunted after three months, than after 14 months (P < 0.05). The minimal heart rate and the difference between the maximal and the minimal heart rate during the 24-h electrocardiography were significantly correlated to the number of normal physiological tests (r = -0.52; P < 0.05; r = 0.71; P < 0.005); for the maximal heart rate, there was a positive trend only (r = 0.44; P = 0.07). Early after the maze procedure, a nearly total denervation of the sinus node is present, similar as seen after heart transplantation, with partial restoration of the autonomic function after one year. The exercise capacity of the patients was satisfactory.

Very low frequency oscillations in arterial blood pressure after autonomic blockade in conscious dogs.

The aim of this study was to investigate spontaneous variability of arterial blood pressure in conscious foxhounds in the absence of direct sympathetic and parasympathetic influences. Autonomic blockade was achieved by administration of the ganglionic blocking agent hexamethonium (n = 7). In contrast to the control group (n = 7), marked oscillations with a cycle length of 100 s (0.01 Hz) were observed. The relationship of the power densities of the oscillation band (0.01 +/- 0.005 Hz) to the total power increased threefold (0.213 +/- 0.007 vs. 0.057 +/- 0.005; P < 0.01). The 0.01-Hz oscillations typically commenced after some delay. To test whether the absence of the mechanoreceptor afferents was responsible for these fluctuations, we investigated an additional group of foxhounds that were subjected to total baroreceptor and cardiopulmonary receptor denervation (n = 7). Neither in this protocol, nor in a group subjected to denervation and ganglionic blockade (n = 6), did we observe sustained oscillations in this frequency range. Since the oscillations were not seen after combined afferent (mechanoreceptor denervation) and efferent (ganglionic) blockade, central oscillators as a source of the oscillations can be ruled out. A simple model of a circulating pressoric factor may explain the fluctuations, provided that there is a time delay between the stimulus and the release or action of the factor. The findings suggest that a circulating factor accounts for the 0.01-Hz oscillations, which is dependent on intact pathways from the cardiac receptors or baroreceptors to the central nervous system. This hypothesis is put forward since cardiopulmonary and baroreceptor denervation blocked the oscillations seen after ganglionic blockade.

Neuronal circuitry between the inferior mesenteric ganglion and lower intestine of the dog.

Neuronal circuitry between the inferior mesenteric ganglion (IMG) and the distal colon as well as the rectum, forming the intestino-intestinal reflex pathway, was investigated in the dog using immunohistochemistry combined with retrograde tract tracing and denervation experiments. Virtually all IMG neurons were tyrosine hydroxylase (TH)-immunoreactive. Of these ganglionic neurons, about 64% were also immunoreactive for calbindin (Calb), some 35% for neuropeptide Y (NPY), and 2% for vasoactive intestinal peptide (VIP). The retrograde tracer experiments revealed that both Calb/TH neurons and NPY/TH neurons projected to the distal colon and the rectum. In these intestinal walls, Calb/TH positive varicose fibers were found in the myenteric and submucous ganglia as well as in the longitudinal muscle layer, while NPY/TH positive fibers were mainly distributed around the vascular walls. Around Calb/TH neurons of the IMG, abundant varicose nerve fibers immunoreactive for VIP, dynorphin (DYN), calcitonin gene-related peptide (CGRP), enkephalin (ENK), substance P (SP) and bombesin (BOM) were distributed. These immunoreactive fibers disappeared after the total denervation of the IMG. After the application of Fast Blue into the IMG or distal stumps of transected lumbar colonic and hypogastric nerves, retrogradely labeled neurons occurred in the myenteric plexus with increasing density along the distal colon and rectum, and were immunoreactive for VIP, DYN, CGRP, ENK, SP or BOM. Double immunostaining of nerve fibers in the distal stumps of the ligated colonic and hypogastric nerves revealed the presence of viscerofugal fibers containing VIP with DYN and/or CGRP and those containing ENK with SP and/or BOM. These results demonstrate for the first time that the efferent limb of the canine intestino-intestinal reflex arch via the IMG consists of Calb-immunoreactive ganglion neurons projecting to the longitudinal muscles in addition to the enteric plexus of the lower intestine and also of NPY-immunoreactive ganglion neurons projecting to the intestinal blood vessels, and that the afferent limb is composed of at least two discrete groups with different peptide contents, i.e., myenteric neurons containing VIP with DYN and/or CGRP and those containing ENK with SP and/or BOM.

Partial striatal dopamine depletion differentially affects striatal substance P and enkephalin messenger RNA expression.

Near total striatal dopamine denervation results in a decrease in substance P and an increase in enkephalin messenger RNA expression in the striatum. It is unknown whether partial depletions of striatal dopamine content produce similar changes in these peptide messenger RNAs. To test whether compensations in dopamine synthesis and release following partial dopamine denervation prevent the lesion-induced alterations in substance P and enkephalin messenger RNAs, varying concentrations of 6-hydroxydopamine were injected unilaterally into the substantia nigra. Seven days after injection of 6-hydroxydopamine (2-16 micrograms) or vehicle, in situ hybridization histochemistry was used to examine tyrosine hydroxylase messenger RNA in the substantia nigra and substance P and enkephalin messenger RNAs in the striatum. The extent of the dopamine depletion was determined by measuring striatal dopamine tissue content. The decrease in tyrosine hydroxylase messenger RNA paralleled the change in striatal tissue dopamine content. Substance P messenger RNA was decreased in all lesioned rats. In contrast, a significant increase in enkephalin messenger RNA was not detected until striatal dopamine was reduced to 10% of control levels. These results suggest that compensations within the residual dopamine system are not sufficient to maintain normal striatal substance P messenger RNA levels in partially denervated animals, but are sufficient to maintain normal striatal enkephalin messenger RNA expression.

Blood-pressure variability is buffered by nitric oxide

The baroreflex constitutes the only hitherto known buffer of rapid blood pressure oscillations. In order to investigate the influence of nitric oxide (NO) and the sinoaortic and cardiopulmonary baroreflex pathways on the dynamic properties of blood pressure control, we determined the power spectra of 24-h blood pressure time series of conscious dogs. This was done in the intact state ( n = 6), during blockade of NO synthesis via the false substrate N G-nitro- l-arginine (( l-NNA), 16.5 ± 2 mg/kg body weight i.v., n = 5) and in animals devoid of baroreceptor reflexes ( n = 5). After l-NNA, blood pressure (BP) increased by roughly 20 mmHg to 137 ± 6 mmHg ( P < 0.01), heart rate decreased from 97 ± 6 to 68 ± 3 beats/min ( P < 0.01). The power of blood pressure variations within the frequency range 0.1–0.5 Hz was tripled by l-NNA ( P < 0.05). By comparison total sinoaortic and cardiopulmonary denervation increased power of slower oscillations (< 0.1 Hz) by a factor of 4.7 ( P < 0.05). Thus, NO and the baroreceptor reflex both play an important role as physiological blood pressure buffers, NO for rapid (0.1–0.5 Hz) and the baroreflex for slower fluctuations (< 0.1 Hz).

Innervated liver plays an inhibitory role in regulation of food intake

With the onset of eating, the associated rise of dopamine in the lateral hypothalamus (LHA-DA) is thought to regulate quantity of food consumed per meal. Early release of LHA-DA induced by eating is facilitated by oronasal stimulation; we propose that the subsequent LHA-DA response induced by nutrients in the portal vein is dampened by the innervated liver. This was tested by measuring LHA-DA in normal rats: during parenteral feeding to bypass oronasal stimulation, while eating during parenteral feeding, and while eating only. Rats had either total liver denervation or sham operation, with placement of a jugular vein catheter and LHA-DA microdialysis cannula. After a 3-week recovery period total liver denervated rats were randomized to parenterally fed, food only, and parenteral plus food groups each with sham-operated controls in which LHA-DA was measured. No difference in LHA-DA release in food only groups occurred between total liver denervated or sham-operated rats. A significantly higher rise in LHA-DA was observed in total liver denervated versus sham-operated rats in parenterally fed (129% +/- 4% versus 116% +/- 2%; p < 0.05) and parenteral plus food (151% +/- 4% versus 134% +/- 4%; p < 0.05) groups. In total liver denervation versus sham operation, an increase in LHA-DA release occurs during parenteral feeding and eating during parenteral feeding, suggesting that innervated liver inhibits LHA-DA release.

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.

Effects of intravenous mepivacaine on renal sympathetic nerve activity in the cat during nitrous oxide and nitrous oxide-halothane anesthesia.

Because hemodynamic responses to systemic mepivacaine may be influenced by sympathetic change and concurrent general anesthesia, the authors directly measured renal sympathetic nerve activity (RSNA) during intravenous administration of mepivacaine in subseizure through seizure doses under N2O-O2 and N2O-O2-halothane anesthesia. Thirty-four cats were randomly assigned to five groups. Groups I-A, I-B, and I-C received incremental subseizure doses of intravenous mepivacaine (2 mg/kg, 5 mg/kg, and 10 mg/kg). Groups II-A and II-B received intravenous infusion of mepivacaine (4 mg/kg/min). Anesthesia was maintained with N2O(70%)-O2 in groups I-A, I-C, and II-A, and with N2O(70%)-O2-halothane (1%) in groups I-B and II-B. Cats in group I-C had undergone total baroreceptor denervation. Heart rate (HR), mean arterial pressure (MAP), and RSNA were measured. In group I-A, MAP did not significantly change with intravenous mepivacaine, though RSNA and HR significantly decreased (P < .05) respectively with 5 mg/kg i.v. and 10 mg/kg i.v. mepivacaine. In group I-C, HR, MAP, and RSNA did not change significantly. In group I-B, HR and MAP decreased with bolus intravenous doses of mepivacaine in a dose-dependent fashion, but RSNA did not change significantly. All cats in group II-A developed seizure by mepivacaine infusion at mean total dose of 28.9 +/- 4.2 mg/kg without significant changes in HR, MAP, or RSNA. In group II-B, mepivacaine infusion resulted in circulatory collapse at mean total dose of 34.3 +/- 4.6 mg/kg without seizure or significant RSNA change. The authors conclude that intravenous mepivacaine induces occasional depression in HR and RSNA during N2O-O2 anesthesia, but in addition induces dose-related circulatory depression during N2O-O2-halothane anesthesia via nonsympathetic mechanism(s).

Wrist denervation: Surgical considerations

We have analyzed the results of 22 total wrist denervations following Wilhelm's technique and a series of 30 patients treated with denervation of the posterior interosseous nerve alone. Results of denervation have been classified depending on the pain (visual analogue scale) as other parameters (mobility and strength) have not been found to have any statistical significance. Results after partial denervation are worse than results achieved by total denervation.

Wrist denervation: Anatomical considerations

In 1966, Wilhelm published a technique of denervation of the wrist joint based on his own anatomical studies of 1958. Other authors have published their experience in wrist denervations with similar results, but there are some discrepancies in descriptions of the innervation of the wrist. We have studied the innervation of the wrist by dissection under magnification on 20 cadaver limbs and by histological examination of five human foetal wrists. Based in our anatomical findings, we have demonstrated that Wilhelm's technique does not achieve total denervation of the wrist.

Complexity and "chaos" in blood pressure after baroreceptor denervation of conscious dogs.

To investigate how arterial baroreceptors affect the dynamic properties of short-term blood pressure control, we determined Lyapunov exponents and correlation dimensions of blood pressure. Two groups of conscious dogs were studied: a control group (n = 7) and a group subjected to total sinoaortic and cardiopulmonary baroreceptor denervation (n = 7). As a measure of variability, standard deviation was determined and power spectra were calculated. In the lower frequency range (f < 0.1 Hz) power density was inversely related to frequency in both groups, indicating "1/f noise." Estimating the correlation dimension via the Grassberger-Procaccia algorithm as a quantification of complexity revealed a decrease after baroreceptor denervation (1.74 +/- 0.2 vs. 3.05 +/- 0.23 control; P < 0.05). Determination of the largest Lyapunov exponents lambda 1, which indicates the sensitive dependence on initial conditions, a hallmark of chaos, also yielded a diminution after denervation (lambda 1 = 0.74 +/- 0.08 vs. 1.85 +/- 0.18, P < 0.01). The results were cross-checked with surrogate data statistics. The null hypothesis, that there is no nonlinear structure in arterial blood pressure time series, was rejected. This shows that after baroreceptor denervation, blood pressure control is less complex and less sensitive to initial conditions ("chaos"). In contrast, variability (standard deviation) is increased (22.2 +/- 3.1 denervation vs. 8.3 +/- 1.4 control; P < 0.05). It is concluded that under physiological conditions, arterial and cardiopulmonary baroreceptors reduce variability of blood pressure, however, at the cost of blood pressure being less predictable. Thus the regulation is more sensitive depending on initial conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Meal patterns and plasma liver enzymes and metabolites after total liver denervations

The liver by way of afferent nerves has been suggested to be a controller of food intake. However, long term meal pattern analysis of chow intake by rats has revealed that total liver denervation (TLD) did not affect the patterns. Nevertheless, these studies have been criticized because they may have missed initial subtle difference in meal patterns that were corrected later by redundant mechanisms. TLD also can alter physiological regulator mechanisms that could secondarily affect feeding behavior. Furthermore, the TLD procedure itself can produce pathologic changes if extreme care is not taken; if pathology does occur it could subsequently affect food intake measurements. In Experiment 1, male rats were given TLD or sham operations (SHAM) at the beginning of the light phase and food withheld until the onset of the dark period. Using a computer operated system, postsurgery onset to feeding, meal size, duration, and frequency were found to be comparable between the groups from the first meal onward. In Experiment 2, 21 days after TLD or SHAM feeding patterns were recorded; all meal parameters were similar between the groups. The rats were then killed and plasma analyzed for liver enzymes (a reflection of liver damage), nutrients and metabolites; no differences were found between the groups. The data suggests that TLD doesn't affect normal regulation of chow intake from the rats' first postsurgery meal onward. The second study showed that the TLD technique, in our hands, did not produce an adverse effect on normal liver function.