Yohimbine in neurally mediated syncope. Pathophysiological implications.

In this study, we evaluated if increased sympathetic stimulation is an essential requirement for the development of neurally mediated syncope (NMS) by manipulating overall sympathetic outflow in subjects susceptible to tilt-induced syncope. Eight previously characterized patients with recurrent NMS (five females and three males; 34+/-2 yr) were recruited from the Vanderbilt Syncope Unit and eight age-matched controls underwent initial administration of clonidine (CLO) or yohimbine (YHO). This was done, prospectively, to determine doses of these agents that would increase or decrease plasma norepinephrine levels by >/= 30%. On a different day, in all subjects we determined intraarterial blood pressure, EKG and muscle sympathetic nerve activity (MSNA) both supine and during upright tilt. After this, subjects randomly received either CLO or YHO, and 3 h later another tilt was performed. After 1 wk, a similar procedure with the other drug was performed. During the two basal tilts, all the control subjects completed the study, whereas all the NMS patients developed syncope. Reduction in sympathetic tone by CLO resulted in a decreased tolerance to tilt in three out of eight controls and in all the NMS patients. In contrast, YHO not only increased basal plasma NorEpi levels and MSNA, but also prevented syncope in seven out of eight patients. In a selected population of patients, increased sympathetic activity is not a prerequisite for the development of syncope. Yohimbine-induced enhancement of sympathetic tone in patients with NMS improves orthostatic tolerance and raises the possibility that this drug may be a useful agent in the treatment of NMS.     

Brain perfusion assessed by 99mTc-ECD SPECT imaging in pediatric patients with neurally mediated reflex syncope

BACKGROUND: The involvement of cardiogenic and neurogenic mechanisms in neurally mediated reflex syncope is well documented. In our previous studies in patients with neurally mediated reflex syncope, we have found evidence for differential regulation of the noradrenergic receptors in tilt-positive and tilt-negative patients. The present work concentrates on the observations of differences in regional brain perfusion using brain SPECT via injecting the patient at the completion of the tilt test. METHODS AND RESULTS: The following study was designed to assess the reduction and regional differences in cerebral blood flow by means of SPECT using technetium-99m labeled V-oxo-1,2-N1ethylenedylbisl-cysteine diethylester (ECD) in patients with an injection during tilt testing. Twenty patients with NMS were included in the study with a mean age of 12.2 years (age range; 8-16 years). HUT was positive in 10 patients and negative in 10 patients. When tilt (+) and tilt (-) were evaluated together, regional cortical/cerebellum ratios were ranging from 0.85 to 1.25 in different cortical areas with highest variability of perfusion index in left frontoparietal cortex. The lowest perfusion index values were observed in the left anterior frontal region followed by the left prefrontal-frontoparietal-anterior, parietal-orbito frontal, and anterior temporal regions where perfusion is predominantly supplied via the anterior and middle cerebral arteries, while these differences did not reach statistical significance in a single dominant region compared to the other regions examined using ANOVA (P > 0.05) with this sample size. Decreases in [99mTc]ECD uptake were more widespread regionally on the left hemisphere than were decreases in right side of the brain. However when tilt- and tilt+ groups were compared, perfusion was significantly lower in the right periinsular posterior parietal and temporal regions (P < 0.05) in tilt + group. CONCLUSION: These tilt induced regional differences in brain perfusion suggest the distinct roles of middle cerebral artery dominant territory-related vasodepressor compensation mechanisms in neurally mediated reflex syncope phenomena where cerebral lateralization of cardiac control and insular ischemia may play an important role.     

Understanding and managing neurally mediated syncope in the adolescent.

Syncope and near-syncopal symptoms are common events in the adolescent population. Syncope is defined as the transient loss of postural tone and consciousness with spontaneous recovery. Although most syncopal events are benign, they can generate extreme anxiety in the adolescent and his or her family. The re-occurrence of these events can have a negative impact on an adolescent's participation in daily activities. Understanding the process of assessment, diagnosis, and management of these teens can enable the school nurse to augment initial assessment and to support the prescribed treatment plan. This knowledge then can be used to help allay the adolescent's anxiety and to support efforts at self-management. This article explores current literature in regards to etiology, diagnosis, and medical treatment, and advocates a self-management protocol for neurally mediated syncope in the adolescent population with support of that plan by the school nurse.     

Efficacy and safety of clonazepam in refractory neurally mediated syncope

Neurally mediated syncope is a complex syndrome that is often difficult to manage using currently available treatment strategies. The efficacy and safety of clonazepam was evaluated in 35 patients with refractory neurally mediated syncope. All patients had syncope (n = 33) or disabling presyncope (n = 2) and a positive head-up tilt table test (HUTT) despite treatment with one or more of the following therapies: beta-blocker, high-salt diet, fludrocortisone, elastic compression stockings, and disopyramide. Clonazepam was initiated at 0.5 mg/day and titrated in 0.25-0.5 mg/day increments for symptom control. Early (first 8 weeks) symptomatic response was achieved in 31 of 35 (89%) patients. Early HUTT reverted to negative in 29 of 35 (83%) patients. Two patients discontinued clonazepam during early follow-up due to side effects. Thirty-three patients received long-term clonazepam therapy. Twenty-five patients had late HUTT with 21 remaining negative. Of the eight patients who did not have late HUTT, one patient discontinued clonazepam prior to HUTT due to side effects. Seven patients refused late HUTT. All seven patients achieved symptomatic control on clonazepam with two requiring dose titration. Of the 21 patients with a negative late HUTT, 18 achieved symptomatic control with two of these patients requiring dose titration. Two patients who had only partial symptom control despite dose titration achieved total symptomatic control with the addition of disopyramide and beta-blockers. Two patients with a negative late HUTT discontinued clonazepam due to side effects. One patient had been symptomatically controlled while the other had recurrent symptoms with dose limiting side effects occurring after clonazepam dose titration. In the 4 patients with a positive late HUTT, 2 patients were symptomatically controlled, 1 patients required combination therapy with a beta-blocker to achieve symptomatic control, and 1 patient discontinued therapy due to side effects. Overall, 29 of 35 (83%) patients continue to receive clonazepam with symptom control. Based on intention-to-treat HUTT results, 21 of 35 (60%) patients were responders. Four patients required clonazepam dose titration and three required combination therapy with clonazepam plus disopyramide and/or a beta-blocker to achieve control. Clonazepam was discontinued in 6 patients, 5 for side effects and 1 following a transient ischemic attack. Clonazepam appears to be an effective therapeutic alternative in patients with refractory neurally mediated syncope. Based on our preliminary findings, a placebo controlled evaluation of clonazepam in neurally mediated syncope is warranted.     

Evaluation of syncope: focus on diagnosis and treatment of neurally mediated syncope

Syncope, defined as a transient loss of consciousness secondary to global cerebral hypoperfusion, is common in the general population. The single most helpful “test” in the evaluation of patients with syncope is a thoughtful history, with recent evidence that structured histories are remarkably effective in arriving at a diagnosis. In addition to the history, physical examination, and electrocardiogram, arriving at a diagnosis of syncope can involve monitoring and provocative strategies. The majority of patients with syncope have neurally mediated syncope and a favourable prognosis. The management of neurally mediated syncope continues to largely revolve around education, avoidance of triggers, reassurance, and counter-pressure maneuvers. The evidence surrounding medical therapy in vasovagal syncope is not strong to date. Pacemaker therapy is reasonable in older patients with recurrent, unpredictable syncope with pauses, but should be considered as a last resort in younger patients.     

Altered fractal behavior and heart rate variability in daily life in neurally mediated syncope

Autonomic imbalance is thought to play an important role in the pathogenesis of neurally mediated syncope (NMS). Heart rate variability (HRV) indices and fractal dimension derived from 24 h ambulatory electrocardiogram (AECG) reflects the cardiac autonomic activity and provides useful information for understanding the pathogenesis of NMS. In this study, we sought the cardiac autonomic activity and the status of fractal dimension in daily life in patients with NMS. The 24 h ambulatory ECG recordings were performed in 36 NMS patients (NMS group) and in 11 healthy volunteers (CTRL group). Six time domain and frequency domain HRV indices were calculated. The regression of log (power) on log (frequency) was also calculated and the slope of the regression line (β) was analyzed in three different periods such as total 24 h, awake and sleep phases. The values of mean RR, SDNN and SDANN were not significantly different, but the values of S.D. index, rMSSD, pNN50 and all the frequency domain HRV indices were significantly higher in NMS group than in CTRL group. For 24–h period, there was no significant difference in the values of β. For awake phase, the value of β was significantly higher in NMS group than in CTRL group. For sleep phase, the value of β was significantly lower in NMS group than in CTRL group. Augmented autonomic activity and the deterioration of fractal dimension in daily life might contribute to the pathogenesis of NMS.     

Heart rate variability in patients presenting with neurally mediated syncope in an emergency department

BackgroundNeurally mediated syncope (NMS) is a disorder of autonomic nervous system (ANS) regulation. Orthostatic stress is one of the most common causative factors seen in clinical practice. Analysis of heart rate variability (HRV) is a non-invasive method that is used to assess ANS regulation. In this study, we investigated the pathophysiology of NMS using HRV in our emergency department.MethodsThe subjects were 19 patients (age 25.8 ± 6.2 years old) who presented with NMS and 20 healthy individuals (age 26.6 ± 2.7 years old) who served as controls. HRV was measured in supine, sitting and standing positions. Heart rate (HR), low frequency (LF 0.04–0.15 Hz), high frequency (HF > 0.15 Hz), and coefficient of variation of the R-R interval (CVRR) were determined.ResultsLF and HF in the supine position were significantly lower in the patients with NMS (p < 0.05). HR was higher in all positions in patients with NMS than in healthy individuals (p < 0.05). CVRR in the supine position was lower in the patients with NMS (p < 0.001), and it was significantly lower in patients who were positive in an orthostatic test (p = 0.0017). Area under the curve was calculated to be 0.824, and at the cutoff value of 4.997 of CVRR in supine, the sensitivity and the specificity were 78.9% and 85.0%.ConclusionThe sympathetic and parasympathetic nervous systems were both suppressed in patients with NMS. In post-syncope, parasympathetic withdrawal, rather than sympathetic reactivation, was responsible for the increased HR after syncope. CVRR may serve as a new clinical biomarker in the emergency department.     

冠状动脉介入治疗出现神经介导性晕厥的原因分析与护理

冠心病是冠状动脉出现了硬化、狭窄,血流不畅,进而出现心绞痛、心肌梗死,甚至危及生命。冠状动脉介入治疗是打开阻塞血管,重建缺血心肌血运,尽量避免行冠状动脉搭桥术,可以最大限度地减少急性心肌梗死及死亡的发生率[1]。但在介入治疗过程中,病人常可出现面色苍白、出汗、恶心、呕吐、血压下降、     

Psychological and physiological factors associated with tilt table testing for neurally mediated syncopal syndromes

This study investigated psychological and physiological factors in two groups of patients who had tilt table testing for autonomic dysfunction. The first group of 61 patients completed assessments of depression, anxiety, and symptom effects on lifestyle. The 25 patients identified as tilt positive were younger (30.5 years) and had higher mean depression scores (7.6) compared to the tilt-negative response group (n = 36); the latter averaged 40 years of age and had mean depression scores of 4.6. These differences were statistically significant. Women testing tilt positive were significantly more depressed than tilt-negative women (P = 0.02). More severe depressive symptoms were associated with lower blood pressure (BP) (P < 0.05). A second group of 52 patients was monitored during tilt for BP, heart rate (HR), skin temperature (TEMP), skin conductance level (SCL), and forehead muscle tension (EMG). Twenty-seven tested positive and 23 were negative. There were statistically significant group differences in systolic BP and diastolic BP (P < 0.05). There was a significant interaction between tilt status (positive or negative) and time (P = 0.03) in HR. TEMP increased 2 degrees over time in both groups (P < 0.05). The decrease in SCL from 13.7 to 10.4 mu omega in the tilt-positive response group compared to the slight increase in the tilt-negative group was significantly different (P < 0.05). Identification of psychological factors correlated with BP and physiological changes that accompany decreases in BP in tilt-positive response patients could guide management of patients with autonomic dysfunction.     

Respiratory and baroreceptor reflex interactions in man.

Respiratory and arterial baroreceptor reflex interactions were studied in six healthy young adults. Carotid baroreceptors were stimulated with two intensities of neck suction during early inspiration or expiration at 100 or 150% of each subject's normal tidal volume. Sinus node responses to moderate baroreflex stimuli were inhibited by inspiration, but responses to intense stimuli were not influenced by the phase of respiration. Supranormal tidal volume did not diminish responses to inspiratory baroreflex stimuli, but significantly reduced responses to expiratory stimuli. These results provide evidence for a central respiratory baroreceptor reflex interaction in man whose quality is dependent upon the level of afferent baroreceptor activity and the depth of inspiration.     

Selective atrial vagal denervation guided by evoked vagal reflex to treat refractory vasovagal syncope

A 57-year-old woman with refractory vasovagal syncope and a sinus pause of 6.8 seconds during tilt-table test accepted the suggestion of atrial vagal denervation. Radiofrequency pulses were delivered on positive vagal reflex sites according to the standard of heart rate (HR) drop ≥20% after high frequency stimulation (HFS). The endpoint of inexistence of HR decrease at repeating HFS was achieved in 18 sites. No syncope attacked during 12 months and three tilt-table tests performed at 1, 6, and 12 months were negative. Extensive ablation on atrial endocardium for vagal denervation is suggested to be efficient in cardioinhibition type of VVS.     

Diaphragmatic function following cervical cord injury: neurally mediated improvement

Vital capacity measurements from 36 people rendered quadriplegic by traumatic cervical cord injuries generally increased during the first ten months after injury, indicating spontaneous improvement in respiratory muscle function. Reasoning that a renewal of neural supply to the diaphragm would probably be accompanied by a parallel renewal of neural supply to other muscles having adjacent motor pathways, the present study compared vital capacity measurements with concomitant muscle function evaluations from 20 of these people. Qualitatively, increases in vital capacity were invariably accompanied by increases in the function of a group of muscles (primarily of the shoulder and upper arm) having some segmental innervation in common with the diaphragm (C3-C5) but were only sometimes accompanied by increases in the function of a group of muscles (primarily of the forearm and wrist) having segmental innervation below that of the diaphragm (C6-C8). These findings suggest that the spontaneous improvement in vital capacity observed in quadriplegic people is mediated in part by corresponding improvement in the neural supply to the diaphragm. Quantitatively, however, linear regression analysis indicated that neither the rate nor the absolute amount of improvement in vital capacity could be predicted with any reliability from pulmonary function tests, neurologic examinations, or muscle function evaluations performed in the early stage of recovery.     

Psychogenic syncope diagnosed by prolonged head-up tilt testing

Four patients with ‘syncope’ during prolonged headuptilt testing despite normal blood pressure and heart-rate behaviourare described. They represent 5.5% of all positive tilt-testoutcomes from a prospective study of 181 consecutive patientswith unexplained syncope. All four patients were female, andwere both younger and more symptomatic than patients with vasovagalsyncope or orthostatic hypotension. In three of the patients,clinical episodes of syncope were observed which closely resembledthose provoked during tilt. It is suggested that the tilt responseis psychogenic and reveals a psychiatric cause for recurrentsyncope.     

直立倾斜试验对血管迷走性晕厥反复发作的预测价值

目的：探讨直立倾斜试验（HUTT）对血管迷走性晕厥（VVS）反复发作的预测价值。方法：2001年1月-2005年12月在中南大学湘雅二医院晕厥专科门诊就诊或住院的不明原因晕厥患者共429例。根据临床症状分为偶发晕厥组（晕厥发作仅1次，n=112）与反复晕厥组（晕厥发作超过1次，n=317）。HUTT采用基础直立倾斜试验（BHUT）及舌下含服硝酸甘油倾斜试验（SNHUT），观察两组的阳性率与晕厥发作频次的关系。结果：①BHUT＋SNHUT阳性率与晕厥发作频次关系：偶发晕厥组阳性率与反复晕厥组未见差异（36．61％比37．22％），各组男女性别分布亦未见差异（P均〉0.05）。②BHUT或SNHUT阳性率与晕厥发作频次关系：在BHUT时偶发晕厥组阳性率低于反复晕厥组（15．09％比33．33％，P〉0．05），女性〉男性（34．25％比14．15％，P〈0．01）；在SNHUT时偶发晕厥组阳性率亦低于反复晕厥组（10．69％比40．88％，P〉0．05），男女性别未见差异（50．88％比62．35％，P〉0．05）。结论：BHUT和（或）SNHUT与晕厥发作频次无明显关系，HUTT阳性率不能预测VVS反复晕厥发作。     

Complex regional pain syndrome. Sympathetic reflex dystrophy and causalgia

Complex regional pain syndromes (CRPS) occur as the inadequate response to painful trauma in a distal extremity. With CRPS I (sympathetic reflex dystrophy), no lesion of the nerve is present. Aside from sensory disturbances, burning deep spontaneous pain and mechanical allodynia are characteristic. Disturbances in the skin blood circulation,sweating,edema,and trophic disturbances of the skin, joints, and bones are typical. Reduction in muscle strength, tremor, and late dystonic changes comprise the motor disturbances. All symptoms are distributed in the distal extremity and not limited to the region of the peripheral nerves. Complex regional pain syndrome II (causalgia),develops following a partial peripheral nerve lesion. The distally generalized symptoms are identical. Successful therapy depends on an early start of interdisciplinary treatment. In addition to the pain therapy,physiotherapy plays a decisive role in rehabilitation. During the acute phase, freedom from pain at rest and retrogression of the edema must be achieved. With slight spontaneous pain, a conservative therapeutic method may be applied (analgesics, rest, raised position). In case of insufficient improvement and in difficult cases, the effect of intervention (sympathetic blockade) should be tested and possibly a blockade series performed. After reduced spontaneous pain,physiotherapy should be increased stepwise.