Sympathetic Noradrenergic System Research Articles

The possible association between COVID-19 and postural tachycardia syndrome

The possible association between COVID-19 and postural tachycardia syndrome

Autonomic uprising: the tilt table test in autonomic medicine.

This perspective piece on head-up tilt table testing is part of a series on autonomic function testing. The tilt table can be a useful diagnostic test, but methodologies vary, and the results are sometimes misinterpreted. The intent here is not to review comprehensively the utility of various tilt table testing protocols but to convey a number of general points that may give perspective and have practical clinical value, based on an understanding of autonomic physiology and our long clinical and research experience in the evaluation of autonomic disorders. The goals of tilt table testing are to assess orthostatic hypotension (OH), chronic orthostatic intolerance (COI), and unexplained syncope. The testing is useful for distinguishing neurogenic from non-neurogenic OH, identifying failure of the sympathetic noradrenergic system in autonomic neuropathies and ganglionopathies, and assessing baroreflex-sympathoneural function in α-synucleinopathies. For COI, the testing can provide objective data related to the patient's symptoms, diagnose postural tachycardia syndrome (POTS), and distinguish POTS from other causes of tachycardia. Provocative tilt table testing can help understand bases for recurrent transient loss of consciousness in patients with syncope, distinguish neurally mediated syncope from psychogenic pseudosyncope, and separate syncope-related convulsion from epileptic seizures. For each of these purposes, the goals, formats, endpoints, and clinical utility are different. As for any autonomic test, tilt table findings must be interpreted in the context of the patient's clinical presentation.

Autonomic Dysfunction in Cancer Cachexia Coincides With Large Fiber Polyneuropathy

ContextCancer cachexia occurs in most patients suffering from solid malignancies. Recent works suggest paraneoplastic mechanisms. Empirical studies also found autonomic dysfunction in cancer patients, but comprehensive evaluation of the peripheral nervous system is lacking. ObjectivesTo further understand the role of the autonomic and peripheral nervous system in cancer cachexia to guide treatment. MethodsWe prospectively investigated cachectic cancer patients for parasympathetic autonomic dysfunction with a time-domain–based analysis of heart rate variability (breathing at rest, deep breath, and in response to the Valsalva maneuver). Blood pressure changes after the Valsalva maneuver were used as a marker of the sympathetic noradrenergic system. Orthostatic hypertension was investigated in response to active standing. We used a noninvasive continuous beat-to-beat heart rate assessment and blood pressure monitoring. The sympathetic cholinergic nervous system was evaluated with the sympathetic skin response. A detailed neurological examination, nerve conduction studies, and electromyography also were conducted. ResultsA total of 13 patients were enrolled (median age 66 years). Median time from inclusion until death was 3.5 months. About 12 of the 13 patients showed abnormal results in at least one autonomic test. Sympathetic noradrenergic and cholinergic abnormalities were discovered in six patients each and five patients had orthostatic hypotension. Only one patient showed abnormal results in parasympathetic cholinergic tests. Asymptomatic large fiber polyneuropathy was detected in eight patients. ConclusionLarge fiber polyneuropathy coincides with autonomic dysfunction in cachectic cancer patients. Our findings suggest a relevant role of sympathetic impairment in cancer cachexia.

Asparagus racemosus modulates the hypothalamic–pituitary–adrenal axis and brain monoaminergic systems in rats

ObjectivesAsparagus racemosus (AR) is classified as an adaptogen, an important medicinal plant and food. Even though AR is widely used as food and nutraceutical, it has only been evaluated in the context of experimental disorders. Hence, the present study was designed to evaluate the effect of standardized methanolic extract of AR (MAR) on experimentally un-manipulated animals to observe the per se effects on stress pathways.MethodsMAR (50, 100, and 200 mg/kg, per oral) was administered for 7 days. Lorazepam (0.5 mg/kg, intraperitoneal) was used as a positive control. On the seventh day, plasma was collected for the estimation of corticosterone (CORT) and norepinephrine (NE), and brain was microdissected into hippocampus, hypothalamus (HYP), pre-frontal cortex, amygdala, and nucleus accumbens to estimate tissue level of monoamines (serotonin, dopamine, and NE), their metabolites, and turnover.ResultsMAR dose-dependently decreased the plasma CORT and NE levels, indicating its effects on the hypothalamic–pituitary–adrenal cortex axis and the sympathetic-noradrenergic system, respectively. MAR increased the levels of all monoamines in the HYP. However, MAR showed region-specific changes in monoamines and their metabolites, and turnover in other brain regions.DiscussionMAR showed a physiological modulation of the stress pathways. Interestingly, in most brain regions the change in monoaminergic systems was limited by a ceiling effect at a dose of 100 mg/kg. These observations could explain the traditional use of AR as an adaptogen and a functional food.

Impaired glucose tolerance after endurance exercise is associated with reduced insulin secretion rather than altered insulin sensitivity

Paired frequently sampled intravenous glucose tolerance tests (FSIGT) were performed on five highly trained athletes within 2 hours of completing a 6-day ultramarathon run (E) and after 2 weeks of complete rest (R). Severe exercise increased free fatty acid (FFA) levels (E 1.2 ± 0.16 v 0.42 ± 0.07 mmol/L, P < .01) and norepinephrine levels (E 573 ± 141 v 224 ± 33 pg/mL, P < .01), with only moderate reductions in glucose tolerance (glucose disappearance [K g] E 1.06 ± 0.2 v R 1.7 ± 0.3 min −1 × 10 2, P < .05). The minimal model analysis of FSIGT data using the method of Bergman et al (Endocr Rev 6:45–86, 1985) showed a reduced second-phase insulin secretion ([Φ 2] E 5.2 ± 1.3 v 13 ± 2.2 μU/mL · min −2 per mg/dL, P < .05) and glucose disposition index ([SI × Φ 2] E 33.8 ± 10 v 73.9 ± 11 mg −1 · dL · min −3 × 10 4, P < .02). Insulin sensitivity (SI) and glucose-mediated glucose disposal (SG) were unchanged (SI E 6.9 ± 1.0 v 6.0 ± 0.6 min −1 per μU/mL × 10 4; SG E 1.8 ± 0.6 v 1.4 ± 0.3 min −1 × 10 2). Reduced glucose tolerance after prolonged extreme physical exercise was accompanied by reduced Φ 2 and not by alterations of SI or SG, despite the marked increase of FFA levels. Elevated norepinephrine levels, reflecting activation of the sympathetic noradrenergic system, was also associated with the reduction in K g. The reduction in Φ 2 would promote mobilization of FFA, the predominant metabolic substrate in these endurance events.

Effects of intraluminal nutrients on intestinal myoelectric activity in rabbits.

In the unanesthetized rabbit, intraluminal infusions of D- and L-methionine, L-tryptophan, D-glucose, D-xylose, and lactulose had a biphasic effect on small intestinal myoelectric activity. A phase of enhanced activity was followed by a phase of inhibition. The excitatory phase was mimicked by saline solutions equiosmolar to the test solutions. The subsequent inhibition was does dependent and significantly (P less than 0.01) longer for the passively absorbed D-methionine than for the L-stereoisomer. The inhibitory action of 10 mM D-glucose, 10 mM L-methionine, and 5 mM L-tryptophan was blocked by propranolol on the jejunum and by phenoxybenzamine on the ileum. We conclude that the initial excitatory phase induced by luminal amino acids and sugars may be dependent on an action on osmoreceptors, whereas the subsequent inhibitory phase may involve the sympathetic noradrenergic system.

Factors affecting vascular tone

This chapter conveys several concepts and points of view about the scientific and medical significance of differential alterations in activities of components of the autonomic nervous system in stress and disease. The use of terms such as “the autonomic nervous system,” “autonomic failure,” “dysautonomia,” and “autonomic dysfunction” imply the existence of a single entity; however, the autonomic nervous system has functionally and neurochemically distinctive components, which are reflected in differential responses to stressors and differential involvement in pathophysiologic states. One can conceptualize the autonomic nervous system as having at least five components: the sympathetic noradrenergic system, the sympathetic cholinergic system, the parasympathetic cholinergic system, the sympathetic adrenergic system, and the enteric nervous system. Evidence has accumulated for differential noradrenergic vs. adrenergic responses in various situations. The largest sympathetic adrenergic system responses are seen when the organism encounters stressors that pose a global or metabolic threat. Sympathetic noradrenergic system activation dominates the responses to orthostasis, moderate exercise, and exposure to cold, whereas sympathetic adrenergic system activation dominates those to glucoprivation and emotional distress. There seems to be at least as good a justification for the concept of coordinated adrenocortical–adrenomedullary responses as for coordinated adrenomedullary–sympathoneural responses in stress. Fainting reactions involve differential adrenomedullary hormonal vs. sympathetic noradrenergic activation. Parkinson disease entails relatively selective dysfunction of the sympathetic noradrenergic system, with prominent loss of noradrenergic nerves in the heart, yet normal adrenomedullary function. Allostatic load links stress with degenerative diseases, and Parkinson disease may be a disease of the elderly because of allostatic load.