Sympathetic Disruption Research Articles

Cardiovagal baroreflex gain relates to sensory but not neurological level of spinal cord injury

The arterial baroreflex is a primary regulator of autonomic outflow to effectively regulate acute blood pressure changes. After a spinal cord injury (SCI), damage to the autonomic nervous system results in cardiovascular dysregulation. Higher level of injury results in greater loss of sympathetic control, while cardiac parasympathetic control remains intact regardless of injury level. Thus, it is possible that those with high level SCI, and hence extensive sympathetic disruption, will require greater cardiac parasympathetic compensation to control blood pressure. However, the effect of an SCI on cardiovagal baroreflex gain remains unclear. Baroreflex control of blood pressure in those with SCI has been reported to be greater, lesser, and no different compared to able‐bodied individuals. Moreover, the effect of injury level on baroreflex gain remains unclear as most studies that examined the effect of lesion level treated it as a discrete variable – high, usually cervical level lesions, and low, usually thoracic level lesions. Therefore, we assessed baroreflex sensitivity using the neck chamber techniques in those with SCI (N = 29) across a range of injury levels (neurological level of injury C1 – T10, sensory score C4 – S4/5), within 2 years of injury, and compared them to able‐bodied (N = 14). Injury level was assessed by both neurological level of injury and sensory score. We assessed baroreflex gain during 5 trials of 4 levels of neck chamber pressure (corresponding to −15, −25, −35, and −45 mmHg). We found no difference in baroreflex gain between those with SCI and able‐bodied (p>0.1). Neurological level of injury was not correlated to baroreflex gain, but sensory score and resting RR‐interval were (r = 0.47, p<0.01; r = 0.57, p<0.01). Multiple regression showed that both sensory score and resting RR‐interval were strongly predictive of baroreflex gain (r2 = 0.47, p<0.01): gain increased with lower sensory score and higher resting RR‐interval. Moreover, baroreflex gain was not different between those with high and low neurological level of injury; but higher in those with lower compared to higher sensory score (both p<0.01). Hence, sensory score is more predictive of baroreflex gain than the widely used neurological level of injury. This might be understood in the context of vagal‐sympathetic accentuated antagonism: those with high level injuries have the lowest likelihood of intact cardiac sympathetic innervation depressing cardiac vagal responsiveness.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Expression and cellular localization of the transcription factor NeuroD1 in the developing and adult rat pineal gland.

Circadian rhythms govern many aspects of mammalian physiology. The daily pattern of melatonin synthesis and secretion is one of the classic examples of circadian oscillations. It is mediated by a class of neuroendocrine cells known as pinealocytes which are not yet fully defined. An established method to evaluate functional and cytological characters is through the expression of lineage-specific transcriptional regulators. NeuroD1 is a basic helix-loop-helix transcription factor involved in the specification and maintenance of both endocrine and neuronal phenotypes. We have previously described developmental and adult regulation of NeuroD1 mRNA in the rodent pineal gland. However, the transcript levels were not influenced by the elimination of sympathetic input, suggesting that any rhythmicity of NeuroD1 might be found downstream of transcription. Here, we describe NeuroD1 protein expression and cellular localization in the rat pineal gland during development and the daily cycle. In embryonic and perinatal stages, protein expression follows the mRNA pattern and is predominantly nuclear. Thereafter, NeuroD1 is mostly found in pinealocyte nuclei in the early part of the night and in cytoplasm during the day, a rhythm maintained into adulthood. Additionally, nocturnal nuclear NeuroD1 levels are reduced after sympathetic disruption, an effect mimicked by the in vivo administration of α- and β-adrenoceptor blockers. NeuroD1 phosphorylation at two sites, Ser(274) and Ser(336) , associates with nuclear localization in pinealocytes. These data suggest that NeuroD1 influences pineal phenotype both during development and adulthood, in an autonomic and phosphorylation-dependent manner.

Pathophysiology of takotsubo syndrome: Acute cardiac sympathetic disruption (ACSD) syndrome

Pathophysiology of takotsubo syndrome: Acute cardiac sympathetic disruption (ACSD) syndrome

Acute cardiac sympathetic disruption in the pathogenesis of the takotsubo syndrome: A systematic review of the literature to date

Takotsubo syndrome (TS), also known as broken heart syndrome and neurogenic stunned myocardium, is an acute cardiac disease entity characterized by a clinical picture mimicking that of an acute coronary syndrome. The pathogenesis of TS has not been established yet. Among the most often debated pathologic mechanisms of TS are as follows: first, multi-vessel coronary spasm; second, myocardial microvascular dysfunction; third, aborted myocardial infarction caused by transient thrombotic occlusion of a long wrap-around left anterior descending artery; fourth, left ventricular outflow tract obstruction; fifth, blood-borne catecholamine cardiac toxicity; and sixth, cardiac sympathetic disruption and norepinephrine seethe and spillover. The aim of this review is to provide a thorough analysis of the literature data coming mainly from the neurological literature and dealing with the pathogenesis of TS. Substantial evidence challenging the first five hypotheses and arguing in favor of the hypothesis that acute cardiac sympathetic eruption and norepinephrine seethe and spillover is causing TS in predisposed patients is presented.

Insights into the pathogenesis of takotsubo syndrome, which with persuasive reasons should be regarded as an acute cardiac sympathetic disease entity.

The pathogenesis of takotsubo syndrome (TS) has not been established yet. The literature data dealing with the pathogenesis of TS are abundant but scattered among different medical specialities. Subarachnoid hemorrhage and other acute intracranial diseases and injuries are among the important and currently well-recognized trigger factors for TS. In both induced and spontaneous subarachnoid hemorrhages, signs suggestive of increased cardiac sympathetic overactivity have been documented. Surgical and pharmacological sympathectomy has shown to have protective cardiac effects in both animal and human studies. Increase in local release of norepinephrine from the heart of patients with TS has been measured. Signs of both cardiac sympathetic denervation and myocardial lesions adjacent to the cardiac nerve terminals have been seen. Furthermore, the systematized and typically circumferential pattern of ventricular wall motion abnormality is incongruent with the coronary artery supply region and appears most likely to follow the cardiac sympathetic nerve distribution. In conclusion, compelling literature data support the hypothesis that acute cardiac sympathetic disruption and norepinephrine seethe and spillover is causing TS in predisposed patients. TS is most probably an acute cardiac sympathetic disease entity causing myocardial stunning in which takotsubo is one among other cardiac image study findings.

Loss of facial sweating and flushing in Holmes‐Adie syndrome

We investigated pupillary responses to parasympathetic (pilocarpine) and sympathetic agents (tyramine, cocaine, and phenylephrine) in a 51-year-old woman with tonic pupils, loss of muscle stretch reflexes in the limbs, and hemifacial loss of sweating and flushing (Ross' syndrome). A smaller pupillary response to tyramine and cocaine eyedrops on the symptomatic side indicated that outflow was disrupted in the postganglionic section of the ocular sympathetic pathway. A greater response to phenylephrine eyedrops on this side was consistent with denervation supersensitivity to adrenergic agents. Loss of thermoregulatory sweating and flushing and emotional blushing in the forehead, cheek, and chin indicated that sympathetic disruption was proximal to the bifurcation of the common carotid artery, probably in the superior cervical ganglion. A similar degenerative process may be responsible for loss of muscle stretch reflexes, tonic pupils, and other autonomic disturbances in Ross' syndrome.