Comparative Analysis of the Hemodynamic Effects of Remimazolam and Propofol During General Anesthesia: A Retrospective Study.

PURPOSE: Hypotension is common during anesthesia induction. However, minimal hemodynamic effects of remimazolam anesthesia have been reported. We hypothesized that remimazolam would have weaker hemodynamic effects than would propofol. To test this, we simultaneously evaluated the hemodynamics using the estimated continuous cardiac output (esCCO) system and heart rate variability (HRV) during anesthesia induction. METHODS: This was a single-center, observational, retrospective study of patients undergoing dental surgery under general anesthesia between 2020 and 2022. Seventy patients were divided into two groups: remimazolam (R group; n=34) and propofol (P group; n=36). The information obtained from the anesthesia records, patient information, esCCO system parameters, and HRV were integrated and analyzed. The percentages of various parameters were set to 100% for the pre-induction phase as the baseline. RESULTS: The %MAP (noninvasive mean arterial blood pressure) decreased over a narrower range in the R compared to the P group (-17.8% (-26.3%, -11.9%) vs. -22.6% (-32.9%, -17.0%); P=0.039). The %HR (heart rate) increased significantly in the R group and decreased in the P group (+10.7% (+6.5%, +18.6%) vs. -6.5% (-14.5%, +8.4%); P<0.01). The %SVesCCO (stroke volume calculated using the esCCO system) decreased significantly in both groups, but the R group showed a smaller difference compared to the P group (- 5.1% (-7.7%, -2.1%) vs. -10.0% (-13.8%, -5.6%); P<0.01). The rates of change in %LF nu (normalized unit of low frequency) and %HF nu (normalized unit of high frequency) were lower for the R than for the P group, although the difference was not significant (+6.8% (-14.5%, 32.4%) vs. +9.2% (-7.2%, +59.7%), P=0.30; +7.9% (-51.0%, +66.9%) vs. +22.8% (-26.1%, +61.6%), P=0.57). CONCLUSION: Remimazolam demonstrated a lower MAP reduction rate than propofol. A compensatory increase in HR occurred with a decrease in stroke volume. However, the HR increase was not attributable to the autonomic nervous system.

Exploring Head and Neck Paraganglioma: A Case Report.

Paragangliomas (PGLs) are tumors that are rarely malignant; the majority of them are benign. Similar to pheochromocytoma, they develop from the autonomic nerve system. This system originates from neural crest cells and can undergo neoplastic transformation. PGLs can arise either inside or outside the adrenal glands. Head and neck PGLs are very scarce. The primary locations where this tumor commonly originates within this region are the carotid body, jugular bulb, and vagal body. Hence, in our case report, we attempt to highlight the uncommon presentation of this disease in a 46-year-old female, who initially presented with hypertension and persistent dysphonia. The patient underwent successful external radiotherapy. This case report aims to raise awareness of the characteristics of these rare malignancies.

Unveiling the age-related dynamics in Sjögren's syndrome: Insights from heart rate variability and autonomic function.

BACKGROUND: Sjögren's Syndrome (SS), mainly affecting women in their midlife, is characterized by persistent inflammation in glands producing tears and saliva, often leading to significant complications. This study investigates the differences in autonomic system functioning between individuals with SS and healthy controls. METHODS: From April 2019 to December 2022, 329 diagnosed primary SS (pSS) patients and 30 healthy controls were enrolled at Taipei Veterans General Hospital, Taipei, Taiwan. The study assessed autonomic nervous system functioning using various HRV metrics. Participants were divided based on age and AECG criteria, including salivary gland biopsy and autoantibody status. RESULTS: Significant differences in Heart Rate Variability (HRV) were observed between pSS patients and healthy controls. The total power index was notably lower in pSS patients (4.98 ± 1.29) than in controls (5.54 ± 1.21, p = .022). Additionally, Vagal (VAG) activity was significantly reduced in the pSS group (4.95 ± 1.33) compared to the healthy control group (5.47 ± 1.19, p = .041). Age-stratified analysis highlighted that the ≤50 years pSS group had a higher heart rate (77.74 ± 10.42) compared to the >50 years group (73.86 ± 10.35, p = .005). This group also showed a higher total power index (5.78 ± 1.30) versus the >50 years group (4.68 ± 1.19, p < .001), and significantly lower VAG activity (4.70 ± 1.26, p = .007) compared to healthy controls. Furthermore, the Standard Deviation of Normal-to-Normal Intervals (SDNN) was greater in the ≤50 years SS group (44.45 ± 37.12) than in the >50 years group (33.51 ± 26.18, p = .007). In pSS patients, those positive for both salivary gland biopsy and autoantibodies demonstrated a lower Total Power (4.25 ± 1.32) and R-wave validity (93.50 ± 4.79, p < .05) than other groups, suggesting more severe autonomic imbalance. The R-R interval variation (RRIV) was also significantly higher in this dual-positive group (696.10 ± 975.41, p < .05). Additionally, the ESSPRI for dryness was markedly higher in the dual-positive group (8.10 ± 1.45, p < .05), indicating more severe symptoms. These findings reveal significant variations in autonomic function in SS patients, especially in those with dual-positive biopsy and autoantibody status. CONCLUSION: This study demonstrates significant autonomic dysfunction in pSS patients compared to healthy controls, particularly in those positive for both salivary gland biopsy and autoantibodies. The age-stratified analysis further emphasizes the impact of aging on autonomic system functioning in pSS, suggesting a need for age-specific management approaches in pSS patient care.

Associations between Autonomic and Endocrine Reactivity to Stress in Adolescence: Related to the Development of Anxiety?

Internalizing disorders in adolescence have been associated with disturbances in autonomic and endocrine functioning. Because the prefrontal cortex and the limbic system play a central role in regulating both the autonomic and the endocrine systems, their joint functioning is hypothesized to provide information about the potential development of internalizing symptoms throughout adolescence, notably in the preclinical stage. This hypothesis was tested in a sample of 198 adolescents from the general population. Heart rate variability (HRV) and skin conductance levels (SCLs) were measured before, during, and after a public speaking task. These autonomic parameters were associated with cortisol response to the task in the complete sample as well as in low- and high-anxiety adolescents separately. Self-reported social anxiety, low HRV, and high SCL recovery values were predictive of cortisol response. Importantly, in low-anxiety adolescents, only HRV during the task predicted the cortisol response, whereas, in their highly anxious peers, both HRV and SCL were strongly associated with this response. In the latter finding, age was a prominent factor. Additional analyses supported the idea that the interaction of autonomic and endocrine reactivity is subject to natural development. These findings provide evidence that adolescence might be a period of highly interactive emotional-neurobiological development, particularly with respect to the development of stress management skills.

The Dosage Effect of Laser Acupuncture at PC6 (Neiguan) on Heart Rate Variability: A Pilot Study.

Laser acupuncture (LA) has been more applicated in the clinical practice with good responses, but the dosage and parameter settings are still inconsistent with the arguments. This study is focused on the effect of LA on heart rate variability (HRV) with different energy density (ED). Based on the Arndt-Schulz law, we hypothesized that the effective range should fall within 0.01 to 10 J/cm2 of ED, and settings above 10 J/cm2 would perform opposite or inhibitory results. We recruited healthy adults in both sexes as subjects and choose bilateral PC6 (Neiguan) as the intervention points to observe the HRV indexes changes by an external wrist autonomic nerve system (ANS) watch on the left forearm. The data from the ANS watch, including heart rate, blood pressure, and ANS activity indexes, such as low frequency (LF), high frequency (HF), LF%, HF%, LF/HF ratio, and so on, were analyzed by the one-way ANOVA method to test the possible effect. In this study, every subject received all three different EDs of LA in a randomized order. After analyzing the data of 20 subjects, the index of HF% was upward and LF/HF ratio was downward when the ED was 7.96 J/cm2. Otherwise, the strongest ED 23.87 J/cm2 performed the opposite reaction. Appropriately, LA intervention could affect the ANS activities, with the tendency to increase the ratio of parasympathetic and decrease the ratio of sympathetic nerve system activities with statistically significant results, and different ED interventions are consistent with Arndt-Schulz law with opposite performance below and above 10 J/cm2.

Changes in gap junction proteins Connexin30. 2 and Connexin40 expression in the sinoatrial node of rats with dexmedetomidine-induced sinus bradycardia

Abstract Background Dexmedetomidine (Dex) is widely used, and its most common side effect is bradycardia. The complete mechanism through which Dex induces bradycardia has not been elucidated. This research investigates the expression of gap junction proteins Connexin30.2 (Cx30.2) and Connexin40 (Cx40) within the sinoatrial node of rats with Dex-induced sinus bradycardia. Methods Eighty rats were randomly assigned to five groups. Saline was administered to rats in Group C. In the other four groups, the rats were administered Dex to induce bradycardia. In groups D1and D2, the rats were administered Dex at a loading dose of 30 μg.kg−1 and 100 μg.kg−1 for 10 min, then at 15 μg.kg−1.h−1 and 50 μg.kg−1.h−1 for 120 min separately. The rats in group D1A and D2A were administered Dex in the same way as in group D1and D2; however, immediately after the administration of the loading dose, 0.5 mg atropine was administered intravenously, and then at 0.5 mg.kg−1.h−1 for 120 min. The sinoatrial node was acquired after intravenous infusion was completed. Quantitative real-time polymerase chain reaction and western blot analyses were performed to measure mRNA and protein expression of Cx30.2 and Cx40, respectively. Results The expression of Cx30.2 increased, whereas the expression of Cx40 decreased within the sinoatrial node of rats with Dex-induced sinus bradycardia. Atropine reversed the effects of Dex on the expression of gap junction proteins. Conclusion Dex possibly altered the expression of gap junction proteins to slow down cardiac conduction velocity in the sinoatrial node.

Higher pre-treatment skin sympathetic nerve activity and elevated resting heart rate after chemoradiotherapy predict worse esophageal cancer outcomes.

BACKGROUND: Chemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality. METHODS: Thirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome. RESULTS: We found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA ≥ 0.86 µV) also had poor outcome. CONCLUSIONS: Increased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier: NCT03243448.

Muscarinic receptor regulation of chronic pain-induced atrial fibrillation.

Atrial fibrillation (AF), one of the most common arrhythmias, is associated with chronic emotional disorder. Chronic pain represents a psychological instability condition related to cardiovascular diseases, but the mechanistic linkage connecting chronic pain to AF occurrence remains unknown. Wild-type C57BL/6J male mice were randomly divided into sham and chronic pain groups. Autonomic nerve remodeling was reflected by the increased atrial parasympathetic tension and muscarinic acetylcholine receptor M2 expression. AF susceptibility was assessed through transesophageal burst stimulation in combination with electrocardiogram recording and investigating AERP in Langendorff perfused hearts. Our results demonstrated the elevated protein expression of muscarinic acetylcholine receptor M2 in the atria of mice subjected to chronic pain stress. Moreover, chronic pain induced the increase of atrial PR interval, and atrial effective refractory periods as compared to the sham group, underlying the enhanced susceptibility of AF. Thus, autonomic cholinergic nerve may mediate mice AF in the setting of chronic pain.

Autonomic nervous activity analysis based on visibility graph complex networks and skin sympathetic nerve activity.

Background: Autonomic nerve system (ANS) plays an important role in regulating cardiovascular function and cerebrovascular function. Traditional heart rate variation (HRV) and emerging skin sympathetic nerve activity (SKNA) analyses from ultra-short-time (UST) data cannot fully reveal neural activity, thereby quantitatively reflect ANS intensity. Methods: Electrocardiogram and SKNA from sixteen patients (seven cerebral hemorrhage (CH) patients and nine control group (CO) patients) were recorded using a portable device. Ten derived HRV (mean, standard deviation and root mean square difference of sinus RR intervals (NNmean, SDNN and RMSSD), ultra-low frequency (<0.003 Hz, uLF), very low frequency ([0.003 Hz, 0.04 Hz), vLF), low frequency ([0.04 Hz, 0.15 Hz), LF) and high frequency power ([0.15 Hz, 0.4 Hz), HF), ratio of LF to HF (LF/HF), the standard deviation of instantaneous beat-to-beat R-R interval variability (SD1), and approximate entropy (ApEn)) and ten visibility graph (VG) features (diameter (Dia), average node degree (aND), average shortest-path length (aSPL), clustering coefficient (CC), average closeness centrality (aCC), transitivity (Trans), average degree centrality (aDC), link density (LD), sMetric (sM) and graph energy (GE) of the constructed complex network) were compared on 5-min and UST segments to verify their validity and robustness in discriminating CH and CO under different data lengths. Besides, their potential for quantifying ANS-Load were also investigated. Results: The validation results of HRV and VG features in discriminating CH from CO showed that VG features were more clearly distinguishable between the two groups than HRV features. For effectiveness evaluation of analyzing ANS on UST segment, the NNmean, SDNN, RMSSD, LF, HF and LF/HF in HRV features and the CC, Trans, Dia and GE of VG features remained stable in both activated and inactivated segments across all data lengths. The capability of HRV and VG features in quantifying ANS-Load were evaluated and compared under different ANS-Load, the results showed that most HRV features (SDNN, LFHF, RMSSD, vLF, LF and HF) and almost all VG features were correlated to sympathetic nerve activity intensity. Conclusions: The proposed autonomic nervous activity analysis method based on VG and SKNA offers a new insight into ANS assessment in UST segments and ANS-Load quantification.

Changes in gap junction proteins Connexin30.2 and Connexin40 expression in the sinoatrial node of rats with dexmedetomidine-induced sinus bradycardia.

BACKGROUND: Dexmedetomidine (Dex) is widely used, and its most common side effect is bradycardia. The complete mechanism through which Dex induces bradycardia has not been elucidated. This research investigates the expression of gap junction proteins Connexin30.2 (Cx30.2) and Connexin40 (Cx40) within the sinoatrial node of rats with Dex-induced sinus bradycardia. METHODS: Eighty rats were randomly assigned to five groups. Saline was administered to rats in Group C. In the other four groups, the rats were administered Dex to induce bradycardia. In groups D1 and D2, the rats were administered Dex at a loading dose of 30 µg.kg-1 and 100 µg.kg-1 for 10 min, then at 15 µg.kg-1.h-1 and 50 µg.kg-1.h-1 for 120 min separately. The rats in group D1A and D2A were administered Dex in the same way as in group D1 and D2; however, immediately after the administration of the loading dose, 0.5 mg atropine was administered intravenously, and then at 0.5 mg.kg-1.h-1 for 120 min. The sinoatrial node was acquired after intravenous infusion was completed. Quantitative real-time polymerase chain reaction and western blot analyses were performed to measure mRNA and protein expression of Cx30.2 and Cx40, respectively. RESULTS: The expression of Cx30.2 increased, whereas the expression of Cx40 decreased within the sinoatrial node of rats with Dex-induced sinus bradycardia. Atropine reversed the effects of Dex on the expression of gap junction proteins. CONCLUSION: Dex possibly altered the expression of gap junction proteins to slow down cardiac conduction velocity in the sinoatrial node.

Regulation of the Autonomic Nervous System on Intestine.

Intestine is composed of various types of cells including absorptive epithelial cells, goblet cells, endocrine cells, Paneth cells, immunological cells, and so on, which play digestion, absorption, neuroendocrine, immunological function. Intestine is innervated with extrinsic autonomic nerves and intrinsic enteric nerves. The neurotransmitters and counterpart receptors are widely distributed in the different intestinal cells. Intestinal autonomic nerve system includes sympathetic and parasympathetic nervous systems, which regulate cellular proliferation and function in intestine under physiological and pathophysiological conditions. Presently, distribution and functional characteristics of autonomic nervous system in intestine were reviewed. How autonomic nervous system regulates intestinal cell proliferation was discussed. Function of autonomic nervous system on intestinal diseases was extensively reviewed. It might be helpful to properly manipulate autonomic nervous system during treating different intestinal diseases.

The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: a literature review and perspectives.

Acupuncture is used in the treatment of a variety of inflammatory conditions and diseases. However, the mechanisms of its anti-inflammatory action are complex and have not been systematically investigated. Macrophages are key components of the innate immune system, thus, balancing the M1/M2 macrophage ratio and modulating cytokine levels in the inflammatory environment may be desirable therapeutic goals. Evidence has shown that acupuncture has anti-inflammatory actions that affect multiple body systems, including the immune, locomotory, endocrine, nervous, digestive, and respiratory systems, by downregulating pro-inflammatory M1 and upregulating anti-inflammatory M2 macrophages, as well as by modulating associated cytokine secretion. Macrophage polarization is controlled by the interlocking pathways of extrinsic factors, the local tissue microenvironment, and the neural-endocrine-immune systems. It has been suggested that polarization of T lymphocytes and cytokine secretions resulting in modulation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, may be upstream mechanisms of acupuncture-induced macrophage polarization. We further propose that macrophage polarization could be the principal pathway involved in acupuncture immune regulation and provide the scientific basis for the clinical application of acupuncture in inflammatory conditions.

Positive effects of music therapist's selected auditory stimulation on the autonomic nervous system of patients with disorder of consciousness: a randomized controlled trial.

The current randomized controlled trial was performed at the China Rehabilitation Science Institute, China to test the hypothesis that musical auditory stimulation has positive effects on the autonomic nervous system of patients with disorder of consciousness. Although past studies have recommended that patients with disorder of consciousness listen to patient-preferred music, this practice is not universally accepted by researchers. Twenty patients with severe disorder of consciousness listened to either therapist-selected (n = 10, 6 males and 4 females; 43.33 ± 18.76 years old) or patient-preferred (n = 10, 5 males and 5 females, 48.83 ± 18.79 years old) musical therapy, 30 minutes/day, 5 times/week for 6 weeks. The results showed no obvious differences in heart rate variability-related parameters including heart rate, standard deviation of normal-to-normal R-R intervals, and the root-mean-square of successive heartbeat interval differences of successive heartbeat intervals between the two groups of patients. However, percentage of differences exceeding 50 ms between adjacent normal number of intervals, low-frequency power/high-frequency power, high-frequency power norm, low-frequency power norm, and total power were higher in patients receiving therapist-selected music than in patients receiving their own preferred music. In contrast, this relationship was reversed for the high-frequency power and very-low-frequency band. These results suggest that compared with preferred musical stimulation, therapist-selected musical stimulation resulted in higher interactive activity of the autonomic nervous system. Therefore, therapist-selected musical stimulation should be used to arouse the autonomic nervous system of patients with disorder of consciousness. This study was approved by the Institutional Ethics Committee of China Rehabilitation Research Center, China (approval No. 2018-022-1) on March 12, 2018 and registered with the Chinese Clinical Trial Registry (registration number ChiCTR1800017809) on August 15, 2018.

Association between urinary function and resected pattern of the autonomic nerve system after transanal total mesorectal excision for rectal cancer.

AIM: Transanal total mesorectal excision (TaTME) is expected to improve the quality of total mesorectal excision as well as preserve urinary function. We aimed to study the frequency and risk factors of urinary dysfunction in rectal cancer patients after TaTME. Moreover, we analysed the association between urinary function and resected pattern of the autonomic nerve system (ANS) in TaTME. METHOD: We retrospectively analysed 231 patients who underwent TaTME at our hospital from 2013 to 2018. Independent risk factors for urinary dysfunction were assessed by multivariate analysis. Urinary dysfunction was defined as a condition that requires urethral catheterisation. We intraoperatively judged and classified the preserved or resected pattern of ANS into four categories. RESULTS: The rate of urinary dysfunction after TaTME was 12.1% at discharge. Multivariate analysis revealed that beyond TME and ANS resection were the two major independent risk factors for urinary dysfunction. Total ANS preservation had reduced rates of urinary dysfunction, and all patients were free from catheterisation 6 months post-surgery. There was a higher rate of urinary dysfunction in total ANS resection than in partial ANS resection at 6 months post-surgery. CONCLUSION: This study showed that urinary function after TaTME was associated with resection of the ANS. Furthermore, the rate of urinary dysfunction and recovery time were closely related to the pattern of ANS resection.

Application of the Variance Delay Fuzzy Approximate Entropy for Autonomic Nervous System Fluctuation Analysis in Obstructive Sleep Apnea Patients.

Obstructive sleep apnea (OSA) is a fatal respiratory disease occurring in sleep. OSA can induce declined heart rate variability (HRV) and was reported to have autonomic nerve system (ANS) dysfunction. Variance delay fuzzy approximate entropy (VD_fApEn) was proposed as a nonlinear index to study the fluctuation change of ANS in OSA patients. Sixty electrocardiogram (ECG) recordings of the PhysioNet database (20 normal, 14 mild-moderate OSA, and 26 severe OSA) were intercepted for 6 h and divided into 5-min segments. HRV analysis were adopted in traditional frequency domain, and nonlinear HRV indices were also calculated. Among these indices, VD_fApEn could significantly differentiate among the three groups (p < 0.05) compared with the ratio of low frequency power and high frequency power (LF/HF ratio) and fuzzy approximate entropy (fApEn). Moreover, the VD_fApEn (90%) reached a higher OSA screening accuracy compared with LF/HF ratio (80%) and fApEn (78.3%). Therefore, VD_fApEn provides a potential clinical method for ANS fluctuation analysis in OSA patients and OSA severity analysis.

Severe bradycardia at the termination of seizure during electroconvulsive therapy.

BACKGROUND: Few cases of asystole or severe bradycardia occurring after the termination of seizure in the third phase with the dominance of parasympathetic nervous system activity during electroconvulsive therapy (ECT) have been reported. We describe a case of severe bradycardia occurring at the termination of seizure. CASE PRESENTATION: The patient had been diagnosed with bipolar disorder more than 9 years earlier. No adverse hemodynamic events had been observed in over 100 sessions of ECT performed during a 9-year period. ECT was usually induced by propofol and suxamethonium. On this ECT, the heart rate gradually decreased before seizure termination, and severe bradycardia (5-6 beats/min) was identified lasting 15-20 s. Atropine administration immediately before electrical stimulus prevented any further bradycardia during the next session of ECT. CONCLUSIONS: This case report indicates that attention should be paid to adverse cardiac events related to autonomic nerve activity even before such events occur during ECT.

Headache and Left Ventricular Efficiency After Transcatheter Closure of Atrial Septal Defect.

OBJECTIVE/BACKGROUND: This study aimed to clarify the relationship between migraine-like headache and ventriculo-arterial coupling after transcatheter closure of the atrial septal defect in children. We hypothesized that migraine headache after defect closure would be related to an abnormal hemodynamic response against an increased left ventricular filling. DESIGN: A retrospective cohort study. METHODS: We calculated the end-ventricular systolic elastance (Ees), effective arterial elastance (Ea), and ventricular energy efficiency approximated based on echocardiography before and after defect closure, and compared these parameters between the subjects with and without headache after defect closure. RESULTS: A total of 167 subjects were studied. Age at the procedure, defect diameter, and pulmonary to systemic blood flow ratio were 11 (9-17) years, 12.8 (9.2-16.0) mm, and 1.8 (1.6-2.3), respectively. We identified 47 (28%) subjects with migraine headache after defect closure. Although there was no significant difference in the Ees, Ea, and ventricular energy efficiency before defect closure between the groups, the Ees (4.0 [3.4-4.9] vs 4.8 [3.7-6.1], P = .014) and ventricular energy efficiency (0.79 [0.76-0.82] vs 0.83 [0.79-0.85], P = .001) after defect closure in subjects with headache were significantly lower than those in subjects without headache. Migraine headache after defect closure was significantly associated with age (odds ratio: 0.97, 95% confidential interval: 0.94-1.00, P = .036) and a decrease in the ventricular energy efficiency after defect closure (odds ratio: 6.42, 95% confidential interval: 2.76-14.90, P < .001). CONCLUSION: A loss of ventricular energy efficiency was common in pediatric subjects with migraine-like headache after transcatheter closure of the atrial septal defect, which suggested that the left ventricular function maladaptation was related to headache development after defect closure. We advocate that an impaired ventriculo-arterial coupling may be one of the mechanisms for developing attacks in not only this population but also in other patients with migraine.

Phosphorylated Alpha-Synuclein Within Cutaneous Autonomic Nerves of Patients With Parkinson's Disease: The Implications of Sample Thickness on Results.

The detection of cutaneous phosphorylated alpha-synuclein (P-syn) in patients with Parkinson's disease (PD) has ranged from 30% to 100% across different studies. We hypothesize that part of the variability in P-syn detection is due to methodological differences using sections of different tissue thickness. Three skin biopsies were obtained from 29 individuals with PD and 21 controls. Tissues were cut into 10-, 20-, and 50-µm-thick sections and double-stained with protein gene product (PGP) 9.5 and P-syn. We quantified the deposition of P-syn with and without PGP 9.5 in sweat glands, pilomotor muscle, and blood vessels using confocal digital images of autonomic structures. Overall, the P-syn-positive rates with PGP 9.5 colocalization in subjects with PD were 100% using 50 µm sections, 90% using 20 µm sections, and 73% using 10 µm sections with 100% specificity. (No P-syn was detected within control subjects.) Without PGP 9.5, colocalization of the P-syn-positive rates was 100% for all samples, but specificity dropped below 70%. In this study, double-immunostained 50 µm skin biopsy tissue sections are superior to 20 and 10 µm tissue sections at detecting P-syn in subjects with PD. The increased sensitivity is likely secondary to a combination of greater volume of tissue analyzed and improved visualization of nerve fiber architecture.

Identification of Cardiac Expression Pattern of Transient Receptor Potential Vanilloid Type 1 (TRPV1) Receptor using a Transgenic Reporter Mouse Model.

Transient receptor potential vanilloid type 1 (TRPV1) channels are structurally related, non-selective cation channels that exhibit a high permeability to calcium. Sensory nerve endings expressing TRPV1 channels play a prominent role in regulating the cardiac sympathetic afferent reflex and contribute to cardiac remodeling and dysfunction in chronic heart failure. However, the precise expression of TRPV1 channels in cardiomyocytes vs. non-cardiomyocytes remains debated. Here we utilized a tdTomato-GFP reporter mouse crossed with a mouse line expressing Cre recombinase under the control of the TRPV1 promoter to map the TRPV1 expression pattern in heart. In this model, TRPV1-negative cells express tdTomato protein (red), whereas TRPV1-positive cells express GFP protein (green). As we expected, substantial GFP expression was found in many small and medium diameter dorsal root ganglia neurons in heterozygous TRPV1-Cre +/-, tdTomato flox/flox +/- male mice, suggesting that this heterozygous model is sufficient for labeling TRPV1-positive cells. Furthermore, these results showed that GFP green staining was not detectable in cardiomyocytes. Instead, we found strong GFP green staining in cardiac blood vessels-thought to be arterioles-in the heart. We also observed strong GFP signals on PGP9.5-positive cardiac nerve endings in the epicardium. In summary, this study does not support the concept that TRPV1 channels are strongly expressed in mouse cardiomyocytes. We conclude that TRPV1 channels in mouse heart are mostly expressed on non-cardiomyocyte cells including cardiac nerve endings and vessels. These data have important implications for the modulations of cardiogenic reflexes.