Autonomic Neuroscience-Basic & Clinical最新文献

{"title":"Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and postural orthostatic tachycardia syndrome: A retrospective study","authors":"Jeffrey P. Moak ,&nbsp;Carolyn B. Ramwell ,&nbsp;Heather Gordish-Dressman ,&nbsp;Sangeeta D. Sule ,&nbsp;Elizabeth Bettini","doi":"10.1016/j.autneu.2024.103163","DOIUrl":"10.1016/j.autneu.2024.103163","url":null,"abstract":"<div><h3>Purpose</h3><p>To determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of neuropathic discomfort (pain, paresthesia and/or allodynia): 1) the incidence of small fiber neuropathy, and 2) assess if there was serologic evidence for an underlying inflammatory or autoimmune state.</p></div><div><h3>Methods</h3><p>A cohort of 109 CAYA patients with the above symptoms underwent epidermal skin biopsy for nerve fiber density. Blood biomarkers for inflammation were tested (CRP, ESR, ANA, complement (C3), thyroid function testing with antibodies (thyroid peroxidase antibody and thyroglobulin antibody), and cytokine panel 13). Patients completed a Quality of Health questionnaire. Statistical analysis was performed using Wilcoxon rank sum tests.</p></div><div><h3>Results</h3><p>In CAYA patients with OI or POTS and neuropathic symptoms, skin biopsy for small fiber neuropathy was abnormal in 53 %. The sample population was predominantly female and Caucasian with moderately decreased perceived quality of health. OI /POTS patients with small fiber neuropathy had a 3-fold probability of having a positive ANA or anti-thyroid antibody, suggesting an underlying autoimmune or inflammatory process.</p></div><div><h3>Conclusion</h3><p>Our data suggest a link between OI and POTS and small fiber neuropathy. Small fiber neuropathy was found by skin biopsy in over half of the patients tested. OI and Postural orthostatic tachycardia patients with small fiber neuropathy expressed multiple markers suggesting an underlying autoimmune or inflammatory process. Future research will be done to evaluate the symptomatic implication of SFN and whether immune or pharmacologic manipulation can alter patient symptoms.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"253 ","pages":"Article 103163"},"PeriodicalIF":2.7,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140076920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vagus nerve stimulation alleviates cardiac dysfunction and inflammatory markers during heart failure in rats","authors":"Misty M. Owens ,&nbsp;Suman Dalal ,&nbsp;Aleksandra Radovic ,&nbsp;Luciano Fernandes ,&nbsp;Hassan Syed ,&nbsp;Mary-Katherine Herndon ,&nbsp;Coty Cooper ,&nbsp;Krishna Singh ,&nbsp;Eric Beaumont","doi":"10.1016/j.autneu.2024.103162","DOIUrl":"10.1016/j.autneu.2024.103162","url":null,"abstract":"<div><p>Vagus nerve stimulation (VNS) is under clinical investigation as a therapy for heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate its therapeutic effects on three main components of heart failure: cardiac function, cardiac remodeling and central neuroinflammation using a pressure overload (PO) rat model. Male Sprague-Dawley rats were divided into four groups: PO, PO + VNS, PO + VNS sham, and controls. All rats, except controls, underwent a PO surgery to constrict the thoracic aorta (~50 %) to induce HFrEF. Open loop VNS therapy was continuously administered to PO + VNS rats at 20 Hz, 1.0 mA for 60 days. Evaluation of cardiac function and structure via echocardiograms showed decreases in stroke volume and relative ejection fraction and increases in the internal diameter of the left ventricle during systole and diastole in PO rats (<em>p</em> &lt; 0.05). However, these PO-induced adverse changes were alleviated with VNS therapy. Additionally, PO rats exhibited significant increases in myocyte cross sectional areas indicating hypertrophy, along with significant increases in myocardial fibrosis and apoptosis, all of which were reversed by VNS therapy (<em>p</em> &lt; 0.05). Furthermore, VNS mitigated microglial activation in two central autonomic nuclei: the paraventricular nucleus of the hypothalamus and locus coeruleus. These findings demonstrate that when VNS therapy is initiated at an early stage of HFrEF progression (&lt;10 % reduction in relative ejection fraction), the supplementation of vagal activity is effective in restoring multi organ homeostasis in a PO model.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"253 ","pages":"Article 103162"},"PeriodicalIF":2.7,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140087947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal dysfunction in the valproic acid induced model of social deficit in rats","authors":"Ashley N. Varley ,&nbsp;Kirsteen N. Browning","doi":"10.1016/j.autneu.2024.103161","DOIUrl":"10.1016/j.autneu.2024.103161","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD) has increased in incidence over the past several decades, and is associated with a range of co-morbidities including gastrointestinal (GI) dysfunctions including gastroesophageal reflux, abdominal pain, bloating, constipation and/or diarrhea. Several animal models have been used that replicate several aspects of ASD but no single model has been able to replicate the entire disease pathophysiology. In humans, prenatal exposure to valproic acid (VPA) has been identified as a significant risk factor and rodent models have shown that in utero VPA exposure leads to behavioral deficits in offspring. The present study aimed to investigate whether in utero exposure to VPA induces GI dysfunction in rats. Timed pregnant Sprague-Dawley rats were injected with a single dose of VPA at embryonic day 12.5. Both male and female offspring subsequently underwent behavioral studies and assessment of GI function in adulthood. In utero VPA treatment induced social deficits in both male and female offspring, decreasing sociability and social novelty. Histological examination showed that VPA treated offspring had decreased thickness of GI muscle and mucosa, while immunohistochemical studies showed a decrease in myenteric neuron number in the fundus. Functional studies showed that both male and female VPA offspring had a delay in gastric emptying compared to vehicle treated offspring. Results of the current study suggest that the rat VPA model of behavioral deficits may be a convenient model by which both mechanistic and functional insights into GI dysfunction may be studied.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"253 ","pages":"Article 103161"},"PeriodicalIF":2.7,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical localization of P2Y12 purinoceptors in the rat carotid body","authors":"Takuya Yokoyama ,&nbsp;Tomoyuki Saino ,&nbsp;Nobuaki Nakamuta ,&nbsp;Yoshio Yamamoto","doi":"10.1016/j.autneu.2024.103158","DOIUrl":"10.1016/j.autneu.2024.103158","url":null,"abstract":"<div><p>The present study investigated the localization of the adenosine 5′-diphosphate (ADP)-selective P2Y12 purinoceptors in the rat carotid body using multilabeling immunofluorescence. Punctate immunoreactive products for P2Y12 were distributed in chemoreceptive type I cells immunoreactive to vesicular nucleotide transporter (VNUT) or dopamine beta-hydroxylase, but not in S100B-immunoreactive glial-like type II cells. P2Y12 immunoreactivity was localized in cell clusters containing VNUT-immunoreactive type I cells surrounded by the perinuclear cytoplasm and cytoplasmic processes of type II cells immunoreactive for ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2) and NTPDase3, which hydrolyze extracellular nucleotide tri- and/or di-phosphates. In ATP bioluminescence assays using carotid bodies, the degradation of extracellular ATP was attenuated in the presence of the selective NTPDases inhibitor ARL67156, suggesting ATP-degrading activity by NTPDases in the tissue. These results suggest that ATP released from type I cells is degraded into ADP and adenosine 5′-monophosphate by NTPDases expressed in type II cells, and that ADP modulates type I cells via P2Y12 purinoceptors.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"252 ","pages":"Article 103158"},"PeriodicalIF":2.7,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139957285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of cardiovascular functioning following sport-related concussion: A physiological perspective","authors":"Chase J. Ellingson ,&nbsp;M. Abdullah Shafiq ,&nbsp;Cody A. Ellingson ,&nbsp;J. Patrick Neary ,&nbsp;Payam Dehghani ,&nbsp;Jyotpal Singh","doi":"10.1016/j.autneu.2024.103160","DOIUrl":"10.1016/j.autneu.2024.103160","url":null,"abstract":"<div><p>There is still much uncertainty surrounding the approach to diagnosing and managing a sport-related concussion (SRC). Neurobiological recovery may extend beyond clinical recovery following SRC, highlighting the need for objective physiological parameters to guide diagnosis and management. With an increased understanding of the connection between the heart and the brain, the utility of assessing cardiovascular functioning following SRC has gained attention. As such, this review focuses on the assessment of cardiovascular parameters in the context of SRC. Although conflicting results have been reported, decreased heart rate variability, blood pressure variability, and systolic (ejection) time, in addition to increased spontaneous baroreflex sensitivity and magnitude of atrial contraction have been shown in acute SRC. We propose that these findings result from the neurometabolic cascade triggered by a concussion and represent alterations in myocardial calcium handling, autonomic dysfunction, and an exaggerated compensatory response that attempts to maintain homeostasis following a SRC. Assessment of the cardiovascular system has the potential to assist in diagnosing and managing SRC, contributing to a more comprehensive and multimodal assessment strategy.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"252 ","pages":"Article 103160"},"PeriodicalIF":2.7,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1566070224000146/pdfft?md5=658904375d0f0abfd152b22ec4f63d99&pid=1-s2.0-S1566070224000146-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139957284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate and adaptive immune system consequences of post-traumatic stress disorder","authors":"Tatlock H. Lauten ,&nbsp;Tamara Natour ,&nbsp;Adam J. Case","doi":"10.1016/j.autneu.2024.103159","DOIUrl":"10.1016/j.autneu.2024.103159","url":null,"abstract":"<div><p>In the field of psychiatry, biological markers are rarely, if ever, used in the diagnosis of mental health disorders. Clinicians rely primarily on patient histories and behavioral symptoms to identify specific psychopathologies, which makes diagnosis highly subjective. Moreover, therapies for mental health disorders are aimed specifically at attenuating behavioral manifestations, which overlooks the pathophysiological indices of the disease. This is highly evident in posttraumatic stress disorder (PTSD) where inflammation and immune system perturbations are becoming increasingly described. Further, patients with PTSD possess significantly elevated risks of developing comorbid inflammatory diseases such as autoimmune and cardiovascular diseases, which are likely linked (though not fully proven) to the apparent dysregulation of the immune system after psychological trauma. To date, there is little to no evidence that demonstrates current PTSD therapies are able to reverse the increased risk for psychological trauma-induced inflammatory diseases, which suggests the behavioral and somatic consequences of PTSD may not be tightly coupled. This observation provides an opportunity to explore unique mechanisms outside of the brain that contribute to the long-term pathology of PTSD. Herein, we provide an overview of neuroimmune mechanisms, describe what is known regarding innate and adaptive immunity in PTSD, and suggest new directions that are needed to advance the understanding, diagnosis, and treatment of PTSD moving forward.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"252 ","pages":"Article 103159"},"PeriodicalIF":2.7,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1566070224000134/pdfft?md5=e8c08ef2836156e21035ddd37e6c48ce&pid=1-s2.0-S1566070224000134-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139947098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use and effectiveness of exercise for managing postural orthostatic tachycardia syndrome in young adults with joint hypermobility and related conditions: A scoping review","authors":"Karen C. Peebles,&nbsp;Charl Jacobs,&nbsp;Logan Makaroff,&nbsp;Verity Pacey","doi":"10.1016/j.autneu.2024.103156","DOIUrl":"10.1016/j.autneu.2024.103156","url":null,"abstract":"<div><h3>Purpose</h3><p>Postural Orthostatic Tachycardia Syndrome (POTS) is a form of dysautonomia. It may occur in isolation, but frequently co-exists in individuals with hypermobile variants of Ehlers-Danlos Syndrome (EDS) and related conditions (chronic fatigue syndrome [CFS] and fibromyalgia). Exercise is recommended for non-pharmacological POTS management but needs to be individualised. This scoping review explores the current literature on use and effectiveness of exercise-based management for POTS, with specific focus on individuals with joint hypermobility and related conditions who experience hypermobility, and/or pain, and/or fatigue.</p></div><div><h3>Methods</h3><p>A systematic search, to January 2023, of Medline, EMBASE, AMED, CINAHL and the Cochrane library was conducted. Studies that reported on adolescents and adults who had been diagnosed with POTS using standard criteria and underwent an exercise-based training intervention were included.</p></div><div><h3>Results</h3><p>Following full-text screening, 10 articles were identified (2 randomised control trials, 4 comparative studies and 4 case reports). One comparative study reported a small subset of participants with EDS and one case report included an individual diagnosed with CFS; the remainder investigated a wider POTS population. Overall, 3 months of endurance followed by resistance exercise, graduating from the horizontal-to-upright position reduced POTS symptoms and improved quality-of-life.</p></div><div><h3>Conclusion</h3><p>The findings highlight a paucity of higher-level studies documenting exercise for POTS management in people with joint hypermobility and related conditions. Results from the wider POTS population demonstrate exercise is safe and effective. Large, well-designed clinical studies exploring exercise for POTS management adapting to meet the complex musculoskeletal and non-musculoskeletal features of symptomatic joint hypermobility are needed.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"252 ","pages":"Article 103156"},"PeriodicalIF":2.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1566070224000109/pdfft?md5=60a1cd5a11d88fef288c89915ff84ef4&pid=1-s2.0-S1566070224000109-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139877948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring quality of life in postural orthostatic tachycardia syndrome: A conceptual analysis","authors":"William S. Frye ,&nbsp;Brooke Greenberg","doi":"10.1016/j.autneu.2024.103157","DOIUrl":"https://doi.org/10.1016/j.autneu.2024.103157","url":null,"abstract":"<div><p>Postural Orthostatic Tachycardia Syndrome (POTS) is a complex autonomic disorder characterized by an abnormal increase in heart rate upon orthostatic change. While primarily described in its effect on the autonomic and cardiovascular system, it can cause significant functional impairment, leading to a diminished quality of life (QoL). This review paper aims to delve into the multifaceted dimensions of QoL in individuals with POTS by providing a conceptual model to discuss factors influencing QoL. Current QoL assessments used in the POTS population and their findings are described for each domain in this conceptual model. Limitations to this body of research include the literature having no consensus in the most appropriate measure of QoL to use for individuals with POTS, the absence of a POTS-specific measure of QoL, and current measures not assessing concerns germane to this population. The authors emphasize the necessity of a POTS-specific measure to be developed to improve our assessment and understanding of how living with POTS impacts QoL.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"252 ","pages":"Article 103157"},"PeriodicalIF":2.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139744080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional and 123I-MIBG scintigraphy assessment of cardiac adrenergic dysfunction in diabetes","authors":"Thorsten K. Rasmussen ,&nbsp;Per Borghammer ,&nbsp;Nanna B. Finnerup ,&nbsp;Troels S. Jensen ,&nbsp;John Hansen ,&nbsp;Karoline Knudsen ,&nbsp;Wolfgang Singer ,&nbsp;Guillaume Lamotte ,&nbsp;Astrid J. Terkelsen","doi":"10.1016/j.autneu.2024.103155","DOIUrl":"https://doi.org/10.1016/j.autneu.2024.103155","url":null,"abstract":"<div><h3>Objectives</h3><p>To assess the agreement between clinical cardiovascular adrenergic function and cardiac adrenergic innervation in type 2 diabetes patients (T2D).</p></div><div><h3>Methods</h3><p>Thirty-three patients with T2D were investigated bimodally through (1) a standardized clinical cardiovascular adrenergic assessment, evaluating adequacy of blood pressure responses to the Valsalva maneuver and (2) ¹²³I-meta-iodobenzylguanidine (MIBG) scintigraphy assessing myocardial adrenergic innervation measured as early and delayed heart heart/mediastinum (H/M) ratio, and washout rate (WR).</p></div><div><h3>Results</h3><p>T2D patients had significantly lower early and delayed H/M-ratios, and lower WR, compared to laboratory specific reference values. Thirteen patients had an abnormal adrenergic composite autonomic severity score (CASS &gt; 0). Patients with abnormal CASS scores had significantly higher early H/M ratios (1.76 [1.66–1.88] vs. 1.57 [1.49–1.63], <em>p</em> &lt; 0.001), higher delayed H/M ratios (1.64 [1.51:1.73] vs. 1.51 [1.40:1.61] (<em>p</em> = 0.02)), and lower WR (−0.13(0.10) vs −0.05(0.07), <em>p</em> = 0.01). Lower Total Recovery and shorter Pressure Recovery Time responses from the Valsalva maneuver was significantly correlated to lower H/M early (<em>r</em> = 0.55, <em>p</em> = 0.001 and r = 0.5, <em>p</em> = 0.003, respectively) and lower WR for Total Recovery (<em>r</em> = −0.44, <em>p</em> = 0.01).</p></div><div><h3>Conclusion</h3><p>The present study found impairment of sympathetic innervation in T2D patients based on parameters derived from MIBG cardiac scintigraphy (low early H/M, delayed H/M, and WR). These results confirm prior studies. We found a mechanistically inverted relationship with favourable adrenergic cardiovascular responses being significantly associated unfavourable MIBG indices for H/M early and delayed. This paradoxical relationship needs to be further explored but could indicate adrenergic hypersensitivity in cardiac sympathetic denervated T2D patients.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"252 ","pages":"Article 103155"},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1566070224000092/pdfft?md5=5da3b0719cffb69fbb2126a873752793&pid=1-s2.0-S1566070224000092-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139733023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic involvement of noradrenergic neuronal neurotransmitter release in cutaneous vasoconstriction during autonomic dysreflexia in persons with spinal cord injury","authors":"Michelle Trbovich ,&nbsp;Yubo Wu ,&nbsp;Terry Romo ,&nbsp;Wouker Koek ,&nbsp;Dean Kellogg","doi":"10.1016/j.autneu.2024.103154","DOIUrl":"10.1016/j.autneu.2024.103154","url":null,"abstract":"<div><h3>Introduction</h3><p>Autonomic dysreflexia (AD) is a potentially life-threatening consequence in high (above T6) spinal cord injury that involves multiple incompletely understood mechanisms. While peripheral arteriolar vasoconstriction, which controls systemic vascular resistance, is documented to be pronounced during AD, the pathophysiological neurovascular junction mechanisms of this vasoconstriction are undefined. One hypothesized mechanism is increased neuronal release of norepinephrine and co-transmitters. We tested this by examining the effects of blockade of pre-synaptic neural release of norepinephrine and co-transmitters on cutaneous vasoconstriction during AD, using a novel non-invasive technique; bretylium (BT) iontophoresis followed by skin blood flow measurements via laser doppler flowmetry (LDF).</p></div><div><h3>Methods</h3><p>Bretylium, a sympathetic neuronal blocking agent (blocks release of norepinephrine and co-transmitters) was applied iontophoretically to the skin of a sensate (arm) and insensate (leg) area in 8 males with motor complete tetraplegia. An nearby untreated site served as control (CON). Cutaneous vascular conductance (CVC) was measured (CVC = LDF/mean arterial pressure) at normotension before AD was elicited by bladder stimulation. The percent drop in CVC values from pre-AD vs. AD was compared among BT and CON sites in sensate and insensate areas.</p></div><div><h3>Results</h3><p>There was a significant effect of treatment but no significant effect of limb/sensation or interaction of limb x treatment on CVC. The percent drop in CVC between BT and CON treated sites was 25.7±1.75 vs. 39.4±0.87, respectively (<em>P</em> = 0.004).</p></div><div><h3>Conclusion</h3><p>Bretylium attenuates, but does not fully abolish vasoconstriction during AD. This suggests release of norepinephrine and cotransmitters from cutaneous sympathetic nerves is involved in cutaneous vasoconstriction during AD.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"252 ","pages":"Article 103154"},"PeriodicalIF":2.7,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139588323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}