Skin Sympathetic Nerve Activity and the Short-Term QT Interval Variability in Patients With Electrical Storm

Background: Skin sympathetic nerve activity (SKNA) and QT interval variability are known to be associated with ventricular arrhythmias. However, the relationship between the two remains unclear.Objective: The aim was to test the hypothesis that SKNA bursts are associated with greater short-term variability of the QT interval (STVQT) in patients with electrical storm (ES) or coronary heart disease without arrhythmias (CHD) than in healthy volunteers (HV).Methods: We simultaneously recorded the ECG and SKNA during sinus rhythm in patients with ES (N = 10) and CHD (N = 8) and during cold-water pressor test in HV (N = 12). The QT and QTc intervals were manually marked and calculated within the ECG. The STVQT was calculated and compared to episodes of SKNA burst and non-bursting activity.Results: The SKNA burst threshold for ES and HV was 1.06 ± 1.07 and 1.88 ± 1.09 μV, respectively (p = 0.011). During SKNA baseline and burst, the QT/QTc intervals and STVQT for ES and CHD were significantly higher than those of the HV. In all subjects, SKNA bursts were associated with an increased STVQT (from 6.43 ± 2.99 to 9.40 ± 5.12 ms, p = 0.002 for ES; from 9.48 ± 4.40 to 12.8 ± 5.26 ms, p = 0.016 for CHD; and from 3.81 ± 0.73 to 4.49 ± 1.24 ms, p = 0.016 for HV). The magnitude of increased STVQT in ES (3.33 ± 3.06 ms) and CHD (3.34 ± 2.34 ms) was both higher than that of the HV (0.68 ± 0.84 ms, p = 0.047 and p = 0.020).Conclusion: Compared to non-bursting activity, SKNA bursts were associated with a larger increase in the QTc interval and STVQT in patients with heart disease than in HV.

The effect of temperature on the activity of the trigeminal nerve in the rat meningeal sheath

Migraine is a debilitating neurological disorder that affects approximately 1 billion people worldwide. It is known that migraine is associated with the activity of the trigeminal nerve, therefore, many studies are aimed at studying changes in the activity of the meningeal nerve fibers. It is known that inflammatory processes accompanied by temperature rise are often accompanied by headaches. Therefore, we investigated the effect of temperature increase on trigeminal nerve activity. It turned out that temperature increase leads to a significant increase in the frequency of action potentials in the trigeminal nerve. Key words: migraine, trigeminal nerve, cluster analysis, action potential.

The Role of Central Command in the Increase in Muscle Sympathetic Nerve Activity to Contracting Muscle During High Intensity Isometric Exercise

We previously demonstrated that muscle sympathetic nerve activity (MSNA) increases to contracting muscle as well as to non-contracting muscle, but this was only assessed during isometric exercise at ∼10% of maximum voluntary contraction (MVC). Given that high-intensity isometric contractions will release more metabolites, we tested the hypothesis that the metaboreflex is expressed in the contracting muscle during high-intensity but not low-intensity exercise. MSNA was recorded continuously via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve in 12 participants, performing isometric dorsiflexion of the right ankle at 10, 20, 30, 40, and 50% MVC for 2 min. Contractions were immediately followed by 6 min of post-exercise ischemia (PEI); 6 min of recovery separated contractions. Cross-correlation analysis was performed between the negative-going sympathetic spikes of the raw neurogram and the ECG. MSNA increased as contraction intensity increased, reaching mean values (± SD) of 207 ± 210 spikes/min at 10% MVC (P = 0.04), 270 ± 189 spikes/min at 20% MVC (P < 0.01), 538 ± 329 spikes/min at 30% MVC (P < 0.01), 816 ± 551 spikes/min at 40% MVC (P < 0.01), and 1,097 ± 782 spikes/min at 50% MVC (P < 0.01). Mean arterial pressure also increased in an intensity-dependent manner from 76 ± 3 mmHg at rest to 90 ± 6 mmHg (P < 0.01) during contractions of 50% MVC. At all contraction intensities, blood pressure remained elevated during PEI, but MSNA returned to pre-contraction levels, indicating that the metaboreflex does not contribute to the increase in MSNA to contracting muscle even at these high contraction intensities.

Low-Dose Fentanyl Does Not Alter Muscle Sympathetic Nerve Activity, Blood Pressure, or Tolerance During Progressive Central Hypovolemia

Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a pre-syncopal limited progressive lower-body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg•min), which was compared between trials using a paired, two-tailed t-test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model (time [LBNP stage] x trial). LBNP tolerance was not different between trials (Fentanyl: 647 ± 386 vs. Placebo: 676 ± 295 mmHg•min, P=0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: p<0.01, trial: p=0.29, interaction: p=0.94) and reductions in mean BP (time: p<0.01, trial: p=0.50, interaction: p=0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.

Temporal Clustering of Skin Sympathetic Nerve Activity Bursts in Acute Myocardial Infarction Patients

Backgrounds: Acute myocardial infarction (AMI) affects the autonomic nervous system (ANS) function. The aim of our study is to detect the particular patterns of ANS regulation in AMI. We hypothesize that altered ANS regulation in AMI patients causes synchronized neural discharge (clustering phenomenon) detected by non-invasive skin sympathetic nerve activity (SKNA).Methods: Forty subjects, including 20 AMI patients and 20 non-AMI controls, participated in the study. The wide-band bioelectrical signals (neuECG) were continuously recorded on the body surface for 5 min. SKNA was signal processed to depict the envelope of SKNA (eSKNA). By labeling the clusters, the AMI subjects were separated into non-AMI, non-cluster appearing (AMINCA), and cluster appearing (AMICA) groups.Results: The average eSKNA was significantly correlated with HRV low-frequency (LF) power (rho = −0.336) and high-frequency power (rho = −0.372). The cross-comparison results demonstrated that eSKNA is a valid surrogate marker to assess ANS in AMI patients. The frequency of cluster occurrence was 0.01–0.03 Hz and the amplitude was about 3 μV. The LF/HF ratio of AMICA (median: 1.877; Q1–Q3: 1.483–2.413) revealed significantly lower than AMINCA (median: 3.959; Q1–Q3: 1.840–6.562). The results suggest that the SKNA clustering is a unique temporal pattern of ANS synchronized discharge, which could indicate the lower sympathetic status (by HRV) in AMI patients.Conclusion: This is the first study to identify SKNA clustering phenomenon in AMI patients. Such a synchronized nerve discharge pattern could be detected with non-invasive SKNA signals. SKNA temporal clustering could be a novel biomarker to classify ANS regulation ability in AMI patients.Clinical and Translational Significance: SKNA is higher in AMI patients than in control and negatively correlates with parasympathetic parameters. SKNA clustering is associated with a lower LF/HF ratio that has been shown to correlate with sudden cardiac death in AMI. The lack of SKNA temporal clustering could indicate poor ANS regulation in AMI patients.

Autonomic Regulation of Kidney Function

A potential role for the renal innervation was first described in 1859 by Claude Bernard, who observed an increase in urine flow following section of the greater splanchnic nerve, which included the renal nerves. Subsequent studies provided little further clarity, leading Homer Smith in 1951 to declare that the renal innervation had little or no significance in controlling kidney hemodynamic or excretory function. However, since the 1960s, there has been increased attention to how the renal nerves may contribute to the deranged control of blood pressure and heart function cardiovascular diseases. The efferent (sympathetic) nerves have neuroeffector junctions which provide close contact with all vascular and tubular elements of the kidney. Activation of the sympathetic nerves at the resistance vessels, that is, the interlobular arteries afferent and even arterioles, modulates both renal blood flow and glomerular filtration rate; at the juxtaglomerular granular cells, they cause renin release and subsequent angiotensin II generation, and at the tubules there is a neurally stimulated increase in epithelial cell sodium transport. Less is known of the role of the afferent nerves, which primarily innervate the renal pelvis, and to a lesser degree the cortex and medulla. Their role is uncertain but sensory information passing to the brain can influence renal efferent nerve activity, forming the basis of both inhibitory and excitatory reno-renal reflexes. Increasingly, it is perceived that in a range of cardiovascular diseases such as cardiac failure, chronic renal disease, and hypertension, there is an inappropriate sympatho-excitation related to alterations in afferent renal nerve activity, which exacerbates the disease progression. The importance of the renal innervation in these disease processes has been emphasized in clinical studies where renal denervation in humans has been found to reduce blood pressure in resistant hypertensive patients and to ameliorate the progression of cardiac and kidney diseases, diabetes, and obesity and hypertension. The importance of both systemic and renal inflammatory responses in activating the neurohumoral control of the kidney is a continuing source of investigation.