Sympathetic Decentralization Research Articles

Left Ventricular Inotropic Response To An Exertional Challenge After Sympathetic Decentralization In Humans

Purpose: Cardiac sympathetic decentralization is a phenomenon in which supraspinal sympathoadrenal control to the heart is deprived. Dysfunction of the sympathetic nervous system is known to contribute to blood pressure abnormalities, arrhythmias, diminished heart rate variability, restricted peak heart rate, and decreased venous return and stroke volume. Cardiac inotropic insufficiency as a result of sympathetic dysfunction has been less frequently studied. This study aimed to characterize the change in left ventricular (LV) inotropicity from rest to a severe exercise challenge in the sympathetically decentralized heart using complete spinal cord injury (cSCI) as a model. Methods: We present two male cases with cSCI (age: 45 and 30 years, BMI 21.8 and 29.5 kg/m2) and compared them with two male sedentary otherwise healthy individuals (age: 43 and 29 years, BMI 29.2 and 25.6 kg/m2). Subjects underwent an incremental arm-ergometer exercise (iAEE) test to peak volitional exhaustion. All indices of LV inotropicity and hemodynamic loading conditions were assessed at rest, during iAEE and at peak iAEE using bioimpedance cardiography (PhysioFlow® Enduro, Manatec, France). LV inotropic response was characterized by observing the response of the acceleration index (dZ/dt2) in all subjects. Results: dZ/dt2 was observed to be impaired in subjects with cSCI compared to the healthy control counterparts (baseline: 0.39 and 0.44 vs .41 and 0.48; peak; 0.55 and 1.073. vs 0.96 and 0.97, respectively). Concomitant differences in the heart rate (HR) and cardiac output (Q) responses to maximal exercise between the cSCI and control subjects were also observed. HR baseline: 57 and 73 vs 97 and 63 bpm; peak: 123 and 99 vs 176 and 151 bpm, respectively. Q baseline: 4.38 and 6.04. vs 6.93 and 5.35 L/m; peak: 11.3 and 10.3 vs 17.06 and 13.94 L/m, respectively. Conclusions: A dichotomy in both the inotropic and chronotropic responses to exercise was apparent in the subjects with decentralizing cSCI. This preliminary data could underscore a critical dependency on heterometric autoregulation for mechanizing increases in cardiac function response to exercise in complete high-level SCI.

Sympathetic Decentralization after Spinal Cord Injury is Associated with Cardiac Atrophy, Increased Protein Degradation, and Systolic Dysfunction.

Sympathetic Decentralization after Spinal Cord Injury is Associated with Cardiac Atrophy, Increased Protein Degradation, and Systolic Dysfunction.

Sympathetic decentralization after spinal cord injury spares Zucker Diabetic Fatty rats from frank diabetes

IntroductionMetabolic syndrome, characterized by the constellation of visceral obesity, atherogenic dyslipidemia, proinflammatory state, hypertension, and insulin resistance, confers a 5‐fold increase in the risk of type 2 diabetes (T2D). Accumulating data from human and animal studies revealed a strong association between sympathetic nervous system (SNS) activation and different components of metabolic syndrome, such as obesity, hypertension, and insulin resistance. However, it is not clear whether sympathoexcitation is a cause or result of metabolic syndrome and the subsequent T2D. Here we used high thoracic spinal cord injury (SCI) as an effective means for SNS decentralization in order to investigate the potential role of the SNS in the pathogenesis of T2D in an animal model of metabolic syndrome.Method/DesignEighteen male Zucker Diabetic Fatty rats (ZDF‐Leprfa/fa, Metabolic syndrome/T2D animal model) were evenly assigned to two groups: uninjured (Fatty‐Sham), and T3 complete SCI (Fatty‐SCI). Lean Zucker Diabetic Fatty rats (ZDF‐Lepr+, n = 9) acted as controls. T2D development was evaluated using biweekly random blood glucose measurements and oral glucose tolerance test (OGTT) at week 11 post‐injury. Twelve weeks post‐injury, animals were euthanized and blood samples and pancreas tissue were collected for further analyses.ResultsWe found that SCI‐induced SNS decentralization, manifested by a dramatic decline in plasma norepinephrine (P = 0.011), was accompanied by improved glucose tolerance, i.e. decreased glucose area under the curve (AUC, P = 0.001), increased fasting insulin (1.00 ± 0.33 vs. 3.02 ± 1.5 ng/ml, p = 0.011), and augmented insulin response after an OGTT, i.e. increased insulin AUC (P = 0.001) in the Fatty‐SCI group compared to uninjured Fatty‐Sham group. Although Fatty‐Sham and Fatty‐SCI groups exhibited a comparable degree of insulin resistance, Fatty‐SCI had significantly higher β‐cell activity indicated by a significant increase in homeostatic model assessment‐%B (HOMA‐%B) index (P = 0.0064). Pancreatic gene expression analysis revealed that SCI caused a significant reduction in the local expression of inflammatory mediators, i.e. IL‐1β and TNF‐α, which are critical for inhibition of insulin secretion, and induction of β‐cell apoptosis and dysfunction. While SNS decentralization spared the Fatty‐SCI rats from frank diabetes, Fatty‐SCI and Fatty‐Sham rats both exhibited other components of metabolic syndrome, including abdominal obesity and dyslipidemia, as compared to lean rats.Support or Funding InformationThis work has been supported by Michael Smith Foundation for Health Research, Craig H. Neilsen Foundation, Heart and Stroke Foundation of Canada, and the International Collaboration on Repair Discoveries.

The thermic response to food intake in persons with thoracic spinal cord injury.

[Purpose] To investigate the influence of the level of spinal cord injury on the thermic effect of food intake (TEF) in persons with thoracic spinal cord injury. [Subjects and Methods] Seven male subjects with spinal cord injury (SCI; age, 40 ± 6 years) and six able-bodied subjects (AB; age, 37 ± 8 years) volunteered to participate in the present study. The subjects consumed an identical test meal consisting of 7.9 kcal/kg of body weight. Energy expenditure and plasma norepinephrine concentrations were measured over a 3-hour period. [Results] The adjusted TEF at 60 min was almost the same among the three groups [AB, SCI with high thoracic cord (T5–6) injury (HSCI), and SCI with low thoracic cord (T9–12) injury (LSCI)]. Although the LSCI group had almost the same adjusted TEF at 120 min as the AB group, the adjusted TEF at 120 min of the HSCI group was significantly lower than that of the AB group. The changes in plasma norepinephrine concentration and heart rate in response to food intake were similar among the three groups. [Conclusion] SCI at the T5–6 level results in a lower TEF due to sympathetic decentralization.

Synergistic application of cardiac sympathetic decentralization and comprehensive psychiatric treatment in the management of anxiety and electrical storm

We report here, for the first time, two cases demonstrating a synergistic application of bilateral cardiac sympathetic decentralization and multimodal psychiatric treatment for the assessment and management of anxiety following recurrent Implantable Cardioverter Defibrillator (ICD) shocks. In a first case the combination of bilateral cardiac sympathetic decentralization (BCSD), cognitive behavioral psychotherapy and anxiolytic medication was sufficient to attenuate the patient's symptoms and maladaptive behaviors, with a maintained benefit at 1 year. Among the more prominent subjective changes in the post-lesion state we observed a decrease in aversive interoceptive sensations, particularly of the heartbeat. The patient continued to experience cognitive threat appraisals on a frequent basis, although these were no longer incapacitating. In a second case, we report the effect of BCSD on autonomic tone and subjective state. In the post-lesion state we observed attenuated sympathetic responses to the valsalva maneuver, isometric handgrip and mental arithmetic stressor, including decreased systolic and diastolic blood pressure and, decreased skin conductance. Collectively, these preliminary findings suggest that an integrative, multidisciplinary approach to treating anxiety disorders in the setting of ventricular arrhythmias and recurrent ICD shocks can result in sustained improvements in physical, psychological, and functional status. These findings raise the possibility of a potential role for the stellate ganglion in the modulation of emotional experience and afferent transmission of interoceptive information to the central nervous system.

Cognitive performance in hypotensive persons with spinal cord injury

Due to sympathetic de-centralization, individuals with spinal cord injury (SCI), especially those with tetraplegia, often present with hypotension, worsened with upright posture. Several investigations in the non-SCI population have noted a relationship between chronic hypotension and deficits in memory, attention and processing speed and delayed reaction times. To determine cognitive function in persons with SCI who were normotensive or hypotensive over a 24-h observation period while maintaining their routine activities. Subjects included 20 individuals with chronic SCI (2-39 years), 13 with tetraplegia (C4-8) and 7 with paraplegia (T2-11). Individuals with hypotension were defined as having a mean 24-h systolic blood pressure (SBP) below 110 mmHg for males and 100 mmHg for females, and having spent >or=50% of the total time below these gender-specific thresholds. The cognitive battery used included assessment of memory (CVLT), attention and processing speed (Digit Span, Stroop word and color and Oral Trails A), language (COWAT) and executive function (Oral Trails B and Stroop color-word). Demographic parameters did not differ among the hypotensive and normotensive groups; the proportion of individuals with tetraplegia (82%) was higher in the hypotensive group. Memory was significantly impaired (P < 0.05) and there was a trend toward slowed attention and processing speed (P < 0.06) in the hypotensive compared to the normotensive group. These preliminary data suggest that chronic hypotension in persons with SCI is associated with deficits in memory and possibly attention and processing speed, as previously reported in the non-SCI population.

Control of heart rate variability by cardiac parasympathetic nerve activity during voluntary static exercise in humans with tetraplegia

Heart rate (HR) is controlled solely by via cardiac parasympathetic outflow in tetraplegic individuals, who lack supraspinal control of sympathetic outflows and circulating catecholamines but have intact vagal pathways. A high-frequency component (HF; at 0.15-0.40 Hz) of the power spectrum of HR variability and its relative value against total power (HF/Total) were assessed using a wavelet transform to identify cardiac parasympathetic outflow. The relative contribution of cardiac parasympathetic and sympathetic outflows to controlling HR was estimated by comparing the HF/Total-HR relationship between age-matched tetraplegic and normal men. Six tetraplegic men with complete cervical spinal cord injury performed static arm exercise at 35% of the maximal voluntary contraction until exhaustion. Although resting cardiac output and arterial blood pressure were lower in tetraplegic than normal subjects, HR, HF, and HF/Total were not statistically different between the two groups. When tetraplegic subjects developed the same force during exercise as normal subjects, HF and HF/Total decreased to 67-90% of the preexercise control and gradually recovered 1.5 min after exercise. The amount and time course of the changes in HF/Total during and after exercise coincided well between both groups. In contrast, the increase in HR at the start of exercise was blunted in tetraplegic compared with normal subjects, and the HR recovery following exercise was also delayed. It is likely that, although the withdrawal response of cardiac parasympathetic outflow is preserved in tetraplegic subjects, sympathetic decentralization impairs the rapid acceleration of HR at the onset of exercise and the rapid deceleration following exercise.

Sympathetic Activities Influence Blood-Flow Velocity and Resistance in the Rabbit Ophthalmic Artery

The aim of this study was to investigate sympathetic influences on blood-flow velocity and resistance in the rabbit ophthalmic artery during the transition period from the light to the dark phase. Eight (8) New Zealand albino rabbits were entrained to a daily 12-h light and 12-h dark cycle. Blood-flow velocities in the ophthalmic artery were determined at -2 (baseline), 0, 2, and 4 h after the onset of darkness. Pulsed and color Doppler images of the ophthalmic artery were recorded using a 12-MHz linear ultrasound transducer. Resistive index of blood flow was calculated using the peak systolic velocity and the end diastolic velocity. Measurements of intraocular pressure (IOP) were taken, using a pneumatonometer at the same time points. Blood-flow velocity, resistive index, and IOP were also determined in the same rabbits after surgical decentralization of the ocular sympathetic nerves. Compared with the baseline at -2 h, a significant increase in the resistive index of blood flow in the ophthalmic artery occurred at 2 and 4 h after the onset of darkness. Parallel elevations of IOP were observed. After the sympathetic decentralization, peak systolic and end diastolic velocities decreased and resistive indexes increased from the presurgical values in the ophthalmic artery. In the postsurgical rabbits, elevation of IOP was absent during the light-dark transition period. There was also no time-dependent increase of resistive index in the ophthalmic artery. During the light-dark transition period, resistance to blood flow in the rabbit ophthalmic artery increases in parallel to IOP elevation. The removal of sympathetic activities decreases blood-flow velocity, but increases blood-flow resistance. Like the endogenous elevation of IOP, the time-dependent increase of resistance to blood flow in the rabbit ophthalmic artery during the light-dark transition period depends upon, at least partially, ocular sympathetic activities.

Cardiovascular control during voluntary static exercise in humans with tetraplegia.

The purpose of the present study was 1) to investigate whether an increase in heart rate (HR) at the onset of voluntary static arm exercise in tetraplegic subjects was similar to that of normal subjects and 2) to identify how the cardiovascular adaptation during static exercise was disturbed by sympathetic decentralization. Mean arterial blood pressure (MAP) and HR were noninvasively recorded during static arm exercise at 35% of maximal voluntary contraction in six tetraplegic subjects who had complete cervical spinal cord injury (C(6)-C(7)). Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were estimated by using a Modelflow method simulating aortic input impedance from arterial blood pressure waveform. In tetraplegic subjects, the increase in HR at the onset of static exercise was blunted compared with age-matched control subjects, whereas the peak increase in HR at the end of exercise was similar between the two groups. CO increased during exercise with no or slight decrease in SV. MAP increased approximately one-third above the control pressor response but TPR did not rise at all throughout static exercise, indicating that the slight pressor response is determined by the increase in CO. We conclude that the cardiovascular adaptation during voluntary static arm exercise in tetraplegic subjects is mainly accomplished by increasing cardiac pump output according to the tachycardia, which is controlled by cardiac vagal outflow, and that sympathetic decentralization causes both absent peripheral vasoconstriction and a decreased capacity to increase HR, especially at the onset of exercise.

Sympathetic decentralization abolishes increased secretion of immunoglobulin A evoked by parasympathetic stimulation of rat submandibular glands

Salivary secretion of immunoglobulin A (IgA) in response to electrical stimulation of the parasympathetic nerve supply was assessed bilaterally in the submandibular glands of anaesthetized rats 1 week following unilateral pre-ganglionic sympathectomy (decentralization). Nerve-mediated stimulation on the non-denervated side increased IgA secretion several fold above an unstimulated rate of secretion whereas sympathetic decentralization reduced the parasympathetically stimulated secretion of IgA without affecting the basal rate. Glandular levels of IgA were increased following decentralization compared to the control glands. Salivary levels of free secretory component (FSC), the cleaved polymeric immunoglobulin receptor (plgR), were increased by parasympathetic stimulation and reduced by sympathectomy, though not as much as IgA. The decreased secretion of FSC suggests a reduced production of plgR and may account in part, for reduced IgA secretion following long-term removal of sympathetic nerve impulses.

Reflex secretion of proteins into submandibular saliva in conscious rats, before and after preganglionic sympathectomy.

1. An indwelling catheter was placed in the left submandibular duct of rats, under pentobarbitone anaesthesia, and connected to an outflow cannula that emerged above the skull. 2. Saliva was collected from the outflow cannula in conscious rats, the same day after recovery from anaesthesia, under four different reflex conditions: grooming, heat exposure, rejection of a bitter tasting substance and feeding on softened chow, repeated in different orders. 3. Saliva flow was greatest for grooming and least for rejection. Protein concentrations were least with heat but much greater and similar for the other stimulations. Acinar peroxidase activity was high for feeding, intermediate for grooming and rejection, and again lowest with heat. Tubular tissue kallikrein activities were moderately low, being greatest with feeding and least with grooming. Secretory immunoglobulin A (SIgA) concentration was least with heat and similar for the other stimulations. 4. The next day, under pentobarbitone anaesthesia, the left preganglionic sympathetic trunk was sectioned (sympathetic decentralization) and, after recovery, the preceding stimulations were repeated. Flow of saliva showed little change, but protein and peroxidase concentrations and outputs decreased dramatically with grooming, rejection and feeding to levels similar to those with heat, which showed little change. Tissue kallikrein was lowered less dramatically, but the reductions in output were significant except with heat. Patterns of proteins resolved by electrophoresis changed for grooming, rejection and feeding and became similar to saliva from heat, which showed little change. No significant effects on SIgA concentrations occurred. 5. Gland weights from the sympathetically decentralized side were greater than from the intact side at the end of the experiments and histologically showed retention of acinar mucin. 6. Thus reflex sympathetic drive varied with the different stimulations; it was least during heat, but it had pronounced effects on acinar secretion of proteins during the other stimulations. At the same time this sympathetic drive had less impact on tissue kallikrein secretion from tubules and had little influence on flow or the concentration of SIgA secreted.

Modulation of bradykinin-induced mechanical hyperalgesia in the rat by activity in abdominal vagal afferents.

Bradykinin-induced plasma extravasation and mechanical hyperalgesia are sympathetic-dependent components of inflammation. Noxious stimulation has been found to inhibit bradykinin-induced plasma extravasation by activating the hypothalamo-pituitary-adrenal axis. The sensitivity of this nociceptive-neuroendocrine feedback control of inflammation is modulated by activity in subdiaphragmatic vagal afferents. In the present study, we tested the hypothesis that activity in the subdiaphragmatic vagus also modifies bradykinin-induced mechanical hyperalgesia in the rat, using the Randall-Selitto method. Following subdiaphragmatic vagotomy, the baseline paw-withdrawal threshold to mechanical stimulation decreased and bradykinin-induced mechanical hyperalgesia was enhanced. Mechanical hyperalgesia produced by prostaglandin E2, a direct-acting hyperalgesic agent, was not significantly affected by vagotomy. The effect of subdiaphragmatic vagotomy on bradykinin-induced hyperalgesia, but not on baseline paw-withdrawal threshold, was mimicked by coeliac branch vagotomy. Indomethacin blocked the hyperalgesia in normal rats, but not in vagotomized rats, suggesting that bradykinin-induced hyperalgesia in normal rats is mediated by prostaglandins, whose role was unexpectedly diminished after vagotomy. Bradykinin-induced hyperalgesia in normal rats was abolished by lumbar sympathectomy but not by sympathetic decentralization (cutting the preganglionic axons). In rats that were both vagotomized and sympathectomized, hyperalgesia induced by low-dose bradykinin was no longer present. These results demonstrate that vagotomy induces a decrease in baseline mechanical paw-withdrawal threshold and an enhancement of bradykinin-induced mechanical hyperalgesia and suggest that these phenomena are generated by actions in peripheral tissues.

Reorganization of the innervation of the vas deferens after sympathetic decentralization.

Reorganization of autonomic efferent pathways to the rat vas deferens was noted after chronic (30 days) sympathetic decentralization produced by hypogastric nerve (HGN) transection. In normal rats, electrical stimulation of the HGN elicited an increase in vasal pressure (VP) bilaterally, whereas pelvic nerve (PN) stimulation did not alter VP. However, after unilateral HGN transection, stimulation of the PN on the transected side but not on the normal side increased VP. The decentralized vas exhibited larger VP responses to stimulation of the contralateral HGN in comparison with the normal vas. After bilateral HGN transection, PN-induced VP responses were elicited at lower stimulus intensities than in rats with unilateral transections. PN-induced VP responses were blocked by hexamethonium and prazosin but were not altered by atropine. Distension of the vas lumen occurred after decentralization. PN-induced VP responses were not detectable in extremely distended vas. These data indicate that, after degeneration of sympathetic preganglionic axons, decentralized adrenergic ganglion cells are reinnervated by parasympathetic or sympathetic preganglionic pathways and that the reinnervation influences vasal function.

Denervation, but not decentralization, reduces nerve growth factor content of the mesenteric artery.

In the present study we applied an improved nerve growth factor (NGF) extraction method to examine the effects of denervation and sympathetic decentralization on NGF levels in vascular tissue. Adult male Wistar Kyoto rats underwent mesenteric arterial denervation or splanchnic nerve transection. Four days after operation, animals were killed, and the mesenteric artery and coeliac-superior mesenteric ganglia were removed. The arterial adventitia was stripped from the media to measure NGF levels in nerve and smooth muscle separately. A high concentration of NGF was detected in the normal artery, 90% of which was in the adventitial layer. Surgical denervation significantly reduced the NGF levels in the artery and ganglia by 78 and 71%, respectively. However, within the artery the level of NGF was reduced in the adventitia but not in the media. Thus, the large reduction of NGF content resulted from the loss of nerve plexus from the artery. In contrast, decentralization did not alter the NGF content in the artery, in either the adventitia or media. Our results are in marked contrast to previous studies reporting elevated levels of NGF following denervation. This discrepancy is explained by the ability of our new procedure to extract much greater amounts of NGF from the tissue.

Diurnal Blood Pressure Variation in Quadriplegic Chronic Spinal Cord Injury Patients

1. Measurement of blood pressure and heart rate over a 24 h period was performed in 10 quadriplegic spinal cord injury patients and 10 immobilized, neurologically intact orthopaedic subjects by using the Spacelabs 90207 automated ambulatory monitoring system. 2. Systolic and diastolic blood pressure fell significantly at night in orthopaedic subjects but not in quadriplegic patients, and night-time blood pressures were similar in both groups. 3. Cumulative summation of differences from a reference value (cusum analysis) confirmed a markedly diminished diurnal blood pressure variation in the quadriplegic patients. 4. These findings could not be accounted for on the basis of blood pressure variations during chronic postural change. 5. Heart rate fell significantly at night in both groups. 6. The findings suggest that the increase in blood pressure during waking hours in neurologically intact subjects is a consequence of a diurnal variation in sympathetic activity (absent in quadriplegic patients with sympathetic decentralization) which is independent of changes in physical activity.

Parasympathetic postganglionic pathways to the sinoatrial node

Vagal ganglia that innervate the canine sinoatrial node (SAN) have been localized to a fat pad overlying and surrounding the right pulmonary vein complex (PVFP). The ventral epicardial surface of the right atrium was mapped in seven dogs anesthetized with alpha-chloralose after beta-blockade (timolol) and cardiac sympathetic and parasympathetic decentralization. A small, concentric bipolar exploring electrode was used to stimulate (during the atrial refractory period and using trains of five to eight stimuli per beat) systematically in the epicardial regions between the PVFP and the SAN. Changes in SAN rate with stimulation were measured, and the anatomic location was identified on a 150-point grid fitted to conform to size and shape of the atrium. Mapping was performed before and after local (PVFP) and systemic ganglionic blockade (hexamethonium). Data reveal that the primary vagal postganglionic pathways to the sinoatrial nodal region are subepicardial and adjacent to the SAN artery along the sulcus terminalis. Hexamethonium in the PVFP abolishes SAN inhibition during preganglionic vagal excitation, without interrupting vagal suppression of atrioventricular conduction. However, SAN slowing (with varying attenuation) continued to occur after hexamethonium (either PVFP or systemically) when the exploring electrode was applied directly over intramural postganglionic fibers between PVFP and sinus node. Attention is directed to existence of a very few synapses closer to SAN, probably in isolated ganglia immersed in fatty connective tissues along the sulcus terminalis.

Functional and anatomical variability of canine cardiac sympathetic efferent pathways: implications for regional denervation of the left ventricle.

To further elucidate the functional anatomy of canine cardiac innervation as well as to assess the feasibility of producing regional left ventricular sympathetic denervation, the chronotropic and (or) regional left ventricular inotropic responses produced by stellate or middle cervical ganglion stimulation were investigated in 22 dogs before and after sectioning of individual major cardiopulmonary or cardiac nerves. Sectioning the right or left subclavian ansae abolished all cardiac responses produced by ipsilateral stellate ganglion stimulation. Sectioning a major sympathetic cardiopulmonary nerve, other than the right interganglionic nerve, usually reduced, but seldom abolished, regional inotropic responses elicited by ipsilateral middle cervical ganglion stimulation. Sectioning the dorsal mediastinal cardiac nerves consistently abolished the left ventricular inotropic responses elicited by right middle cervical ganglion stimulation but minimally affected those elicited by left middle cervical ganglion stimulation. In contrast, cutting the left lateral cardiac nerve decreased the inotropic responses in lateral and posterior left ventricular segments elicited by left middle cervical ganglion stimulation but had little effect on the inotropic responses produced by right middle cervical ganglion stimulation. In addition, the ventral mediastinal cardiac nerve was found to be a significant sympathetic efferent pathway from the left-sided ganglia to the left ventricle. These results indicate that the stellate ganglia project axons to the heart via the subclavian ansae and thus effective sympathetic decentralization can be produced by cutting the subclavian ansae; the right-sided cardiac sympathetic efferent innervation of the left ventricle converges intrapericardially in the dorsal mediastinal cardiac nerves; and the left-sided cardiac sympathetic efferent innervation of the left ventricle diverges to innervate the left ventricle by a number of nerves including the dorsal mediastinal, ventral mediastinal, and left lateral cardiac nerves. Thus consistent denervation of a region of the left ventricle can not be accomplished by sectioning an individual cardiopulmonary or cardiac nerve because of the functional and anatomical variability of the neural components in each nerve, as well as the fact that overlapping regions of the left ventricle are innervated by these different nerves.

Electrical stimulation of the salivatory nucleus in the rat.

Unilateral electrical stimulation of the salivatory nucleus evoked a secretion from the ipsilateral parotid gland which was well maintained. Flow rate was not affected by sympathetic decentralization or by adrenoceptor antagonists but was abolished by atropine. Protein secretion was reduced by beta-adrenoceptor antagonists but not by sympathetic decentralization or adrenalectomy. In support of previous histochemical findings it is concluded that the cells of the reticular formation are the origin of the preganglionic parasympathetic fibres to the salivary glands but that a beta-adrenoceptor mechanism as yet unidentified is also involved in the protein secretion.

Degeneration activity of the pineal gland after sympathetic denervation.

After removal of the superior cervical ganglia the pineal gland of the rat showed a period of transient increase in activity of serotonin-N-acetyltransferase. This degeneration activity was preceded by a decline of the levels of endogenous noradrenaline and an impairment of the 3H-metaraminol uptake. Twenty-seven hours after sympathetic denervation the levels of the endogenous neurotransmitter were almost completely depleted, while either 24 h or 21 days after denervation total uptake of the tritiated amine decreased to only about 50% of the control values. Previous chronic sympathetic decentralization elicited in the pineal gland post-junctional supersensitivity, as judged by the enhanced degeneration activity observed in decentralized glands after sympathetic denervation. The present findings confirm that, in endocrine glands and similarly to other autonomically innervated organs, acute denervation induces degeneration activity.

Preponderance for either alpha- or beta-adrenoceptor mediated sensitization in the rat submaxillary gland.

The sensitivity of the rat submaxillary gland was examined 3-4 weeks after either parasympathetic decentralization or sympathetic decentralization or denervation. The threshold doses for secretion of saliva of parasympathomimetic (methacholine) and sympathomimetic (noradrenaline, adrenaline, phenylephrine and isoprenaline) drugs were estimated and the amount of saliva secreted in response to supraliminal doses of these drugs was measured. Each type of operation caused the development of a supersensitivity that involved all three types of receptors, i.e. muscarinic cholinoceptors, alpha-adrenoceptors and beta-adrenoceptors. Following parasympathetic decentralization the sensitization was predominantly mediated via alpha-adrenoceptors, and also via cholinoceptors. Following sympathetic decentralization or denervation the postjunctional sensitization was predominantly mediated via beta-adrenoceptors; most of the supersensitivity to noradrenaline, adrenaline and phenylephrine found after sympathetic denervation was of the prejunctional type. An increase in receptor density and an intracellular arrangement where the response of cholinoceptors and alpha-adrenoceptors is mediated via one pathway and the response of beta-adrenoceptors via another are suggested as factors that may be of importance for the development of the postjunctional supersensitivity. The present study shows that the traffic of secretory impulses in the sympathetic nerve is of importance for the level of sensitivity of the secretory cells. Since postjunctional supersensitivity following sympathetic denervation did not exceed that following sympathetic decentralization it is suggested that under normal conditions a continuous release of noradrenaline from the nerve endings is of little importance for the level of sensitivity.