Stimulation Of Autonomic Nervous System Research Articles

Burst Stimulation Evokes Increased Bladder and Urethral Pressure in Patients With Sacral Neuromodulation, Indicating Potential Activation of the Autonomic Nervous System: A Pilot Study

ObjectivesCurrently, sacral neuromodulation (SNM) outcomes are often suboptimal, and changing stimulation parameters might improve SNM efficacy. Burst stimulation mimics physiological burst firing of the nervous system and might therefore benefit patients treated with SNM. The purpose of the present pilot study was to evaluate the effect of various Burst SNM paradigms on bladder and urethral pressure in patients with overactive bladder (OAB) or nonobstructive urinary retention (NOUR). Materials and MethodsThe bladder was filled to 50% of its capacity under general anesthesia in six patients with an implanted sacral lead for SNM purposes. Bladder pressure, and mid- and proximal urethral pressure were measured using conventional (Con-) SNM and various Burst SNM paradigms (10-20-40 Hz interburst frequency) with increasing amplitudes up to 5 mA for Con-SNM and 4 mA for Burst SNM. ResultsBurst SNM caused a substantial increase in both bladder and urethral pressure. In contrast, Con-SNM caused a milder increase in urethral pressure, and only one patient showed a modest increase in bladder pressure. Furthermore, the pressure increase was higher in the proximal urethra than in the midurethra using Burst-SNM, whereas Con-SNM caused comparable increases in proximal and midurethra pressure. ConclusionsBurst SNM induces bladder contraction compared with Con-SNM and induces higher pressure increases in bladder and proximal urethra than does Con-SNM in patients with OAB or NOUR, indicating a higher degree of autonomic nervous system stimulation. The observed responses could not be fully explained by the total charge of the Burst SNM paradigms, which suggests the importance of individual Burst SNM parameters, such as frequency and amplitude. Future studies should assess the feasibility and efficacy of Burst SNM in awake patients.

Acute Effect of Vertebral Manipulation Technique on the Autonomic Nervous System

The term "stress" refers to the state induced by perceiving stimuli that trigger emotional and hormonal responses in the body's balance. In acute stress situations, adrenaline, neurotransmitters, and cortisol are released, causing systemic changes and physiological disruptions, keeping the body alert. Heart rate variability assesses the autonomic nervous system. Joint manipulation, involving high-speed, low-amplitude movements, was chosen based on the patient's dysfunction. The study aimed to assess the immediate effects of this technique on the sympathetic and parasympathetic systems, analyzing heart rate variability in university students in Fortaleza. This cross-sectional, randomized, quantitative study at the Ateneu University Center involved 20 participants divided into two groups: G1 – vertebral manipulation application and G2 – a control group with positioning only. Autonomic nervous system evaluation used a sensor connected to the earlobe and the Inner Balance app. Data was processed by Em Wave and Kubios software before and after manipulation. Range of motion was assessed using Kinovea software. Both groups experienced increased range of motion, with greater improvement in the manipulation group. Both groups showed increased parasympathetic activity and reduced sympathetic stress levels, possibly influenced by manipulation and touch, providing either nerve decompression or direct autonomic nervous system stimulation through touch.

Acute Effect of Vertebral Manipulation Technique on the Autonomic Nervous System

The term "stress" refers to the state induced by perceiving stimuli that trigger emotional and hormonal responses in the body's balance. In acute stress situations, adrenaline, neurotransmitters, and cortisol are released, causing systemic changes and physiological disruptions, keeping the body alert. Heart rate variability assesses the autonomic nervous system. Joint manipulation, involving high-speed, low-amplitude movements, was chosen based on the patient's dysfunction. The study aimed to assess the immediate effects of this technique on the sympathetic and parasympathetic systems, analyzing heart rate variability in university students in Fortaleza. This cross-sectional, randomized, quantitative study at the Ateneu University Center involved 20 participants divided into two groups: G1 – vertebral manipulation application and G2 – a control group with positioning only. Autonomic nervous system evaluation used a sensor connected to the earlobe and the Inner Balance app. Data was processed by Em Wave and Kubios software before and after manipulation. Range of motion was assessed using Kinovea software. Both groups experienced increased range of motion, with greater improvement in the manipulation group. Both groups showed increased parasympathetic activity and reduced sympathetic stress levels, possibly influenced by manipulation and touch, providing either nerve decompression or direct autonomic nervous system stimulation through touch.

Abstract 17126: Role of Aldehydes, Transient Receptor Potential Ankyrin 1, and Catecholamines in Electronic Cigarette-Induced Endothelial Dysfunction in Mice

Although Electronic Nicotine Delivery Systems (ENDS)-derived aerosols induce endothelial dysfunction (ED), the mechanisms and constituents responsible for ED are unknown. Because ENDS use propylene glycol and vegetable glycerin (PG:VG) that thermally decompose into aldehydes, we hypothesized that acrolein and formaldehyde stimulate ED via the sensory transient receptor potential ankyrin-1 (TRPA1) receptor and the autonomic nervous system (ANS). To test this, female wild-type (WT) and TRPA1-null mice were exposed to either filtered air, PG:VG-derived aerosol, acrolein (AC; 1 ppm), or formaldehyde (FA, 5 ppm). Biomarkers of exposure (AC: 3HPMA; FA: 4TCA) and of harm (aortic ED; urinary catecholamines) were measured. The PG:VG and AC exposures significantly increased urinary 3HPMA levels; and the PG:VG and FA exposures significantly increased urinary 4TCA levels vs air controls. Both PG:VG and FA exposures (6h/d x 4d) in WT mice led to aortic ED (-64.6±3.8; –66.7±5.5 % ACh, respectively) vs air control (-81.5±1.5 % ACh); yet AC exposure did not induce ED (-76±2.9 % ACh). Exposures in TRPA1-null mice to PG:VG, AC, or FA did not lead to ED (-93.0±3.6; –82.8±3.1; -86.6±2.8 % ACh; respectively). As an index of ANS activation and a potential mediator of ED, urinary catecholamines (dopamine, DA; norepinephrine, NE; epinephrine, EPI; serotonin, 5HT) and metabolites were measured by UPLC-MS/MS in early (0-3h) and late (3-18h) post-exposure (PE) samples. In WT mice, PG:VG significantly increased early PE urine levels of NE (and two NE metabolites; +1.5-2.5x), DA metabolite (+1.5x), but not EPI nor 5HT; FA exposure increased DA (+3x), EPI (+2.5x), NE and NE metabolites (+1.2-2.5x), 5HT and 5HT metabolite (+2.5x) only in late PE; while AC exposure decreased early PE DA (-73%) and 5HT (-42%) levels. In TRPA1-null mice, PG:VG and AC exposures increased early PE levels of NE (+2x) and depressed EPI and 5HT levels (-40%); whereas FA exposure increased NE (+2x), EPI (+4x), and 5HT (+1.5) levels in late PE. Aldehydes induce ED through time-dependent mechanisms mediated in part by TRPA1 activation and ANS stimulation. These data indicate that ENDS use may increase cardiovascular disease risk via aldehydes generated by PG:VG independent of nicotine and flavorants.

Remote but not Distant: a Review on Experimental Models and Clinical Trials in Remote Ischemic Conditioning as Potential Therapy in Ischemic Stroke.

Stroke is one of the main causes of neurological disability worldwide and the second cause of death in people over 65 years old, resulting in great economic and social burden. Ischemic stroke accounts for 85% of total cases, and the approved therapies are based on re-establishment of blood flow, and do not directly target brain parenchyma. Thus, novel therapies are urgently needed. In this review, limb remote ischemic conditioning (RIC) is revised and discussed as a potential therapy against ischemic stroke. The review targets both (i) fundamental research based on experimental models and (ii) clinical research based on clinical trials and human interventional studies with healthy volunteers. Moreover, it also presents two approaches concerning RIC mechanisms in stroke: (i) description of the underlying cerebral cellular and molecular mechanisms triggered by limb RIC that promote neuroprotection against stroke induced damage and (ii) the identification of signaling factors involved in inter-organ communication following RIC procedure. Limb to brain remote signaling can occur via circulating biochemical factors, immune cells, and/or stimulation of autonomic nervous system. In this review, these three hypotheses are explored in both humans and experimental models. Finally, the challenges involved in translating experimentally generated scientific knowledge to a clinical setting are also discussed.

The unexplored relationship between urinary tract infections and the autonomic nervous system.

Urinary tract infections (UTIs), the majority of which are caused by uropathogenic E. coli (UPEC), are extremely common infections that preferentially effect women. Additional complicating factors, such as catheterization, diabetes, and spinal cord injuries can increase the frequency and severity of UTIs. The rise of antimicrobial resistant uropathogens and the ability of this disease to chronically recur make the development of alternative preventative and therapeutic modalities a priority. The major symptoms of UTIs, urgency, frequency, and dysuria, are readouts of the autonomic nervous system (ANS) and the majority of the factors that lead to complicated UTIs have been shown to impact ANS function. This review summarizes the decades' long efforts to understand the molecular mechanisms of the interactions between UPEC and the host, with a particular focus on the recent findings revealing the molecular, bacteriological, immunological and epidemiological complexity of pathogenesis. Additionally, we describe the progress that has been made in: i) generating vaccines and anti-virulence compounds that prevent and/or treat UTI by blocking bacterial adherence to urinary tract tissue and; and ii) elucidating the mechanism by which anti-inflammatories are able to alleviate symptoms and improve disease prognosis. Finally, the potential relationships between the ANS and UTI are considered throughout. While these relationships have not been experimentally explored, the known interactions between numerous UTI characteristics (symptoms, complicating factors, and inflammation) and ANS function suggest that UTIs are directly impacting ANS stimulation and that ANS (dys)function may alter UTI prognosis.

Anesthesia for electroconvulsive therapy: A Noble approach

Electroconvulsive therapy (ECT) has always proved to be an effective mode of therapy in the field of Psychiatry. Modified ECT is applied in the form of electrical stimulus to the central nervous system; it is associated with acute physiologic response leading to autonomic nervous system stimulation with an initial parasympathetic stimulation followed by a more prominent sympathetic response as well as post-ictal effects like confusion and delirium. The factors governing the efficacy of Modified ECT are the strength of electrical current applied and the duration of the seizure activity. Modified ECT requires the use of general anesthesia and many of the anesthetic drugs also have an effect on the duration of seizure and could adversely affect the efficacy of the Modified ECT treatments. Therefore, there has to be a delicate balance between achieving an adequate anesthetic state and optimal duration of seizure activity.

Low level tragus nerve stimulation is a non-invasive approach for anti-atrial fibrillation via preventing the loss of connexins

Atrial fibrillation (AF) is the most common cardiac arrhythmia, but the mechanism of AF maintenance remains unclear. It has been found that gap junctional remodeling (connexin expression is downregulated and distributed) is closely associated with AF maintenance [ [1] Van der Velden H.M. Ausma J. Rook M.B. Hellemons A.J. van Veen T.A. Allessie M.A. Jongsma H.J. Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. Cardiovasc. Res. 2000; 46: 476-486 Crossref PubMed Scopus (214) Google Scholar ]. Autonomic nervous system stimulation can exert anti-arrhythmia effects [ 2 Thunsiri K. Shinlapawittayatorn K. Chinda K. Palee S. Surinkaew S. Chattipakorn S.C. KenKnight B.H. Chattipakorn N. Application of vagus nerve stimulation from the onset of ventricular fibrillation to post-shock period improves defibrillation efficacy. Int. J. Cardiol. 2014; 176: 1030-1032 Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar , 3 He B. Lu Z. He W. Huang B. Jiang H. Similar effects of vagus nerve stimulation and atrial ganglionated plexi stimulation on ventricular effective refractory period and action potential duration in canine. Int. J. Cardiol. 2013; 168: 5116-5118 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ]. Recently, we reported that cervical low level vagal nerve stimulation (LL-VNS) could suppress AF induced high-frequency stimulation [ [4] Yu L. Scherlag B.J. Li S. Sheng X. Lu Z. Nakagawa H. Zhang Y. Jackman W.M. Lazzara R. Jiang H. Po S.S. Low-level vagosympathetic nerve stimulation inhibits atrial fibrillation inducibility: direct evidence by neural recordings from intrinsic cardiac ganglia. J. Cardiovasc. Electrophysiol. 2011; 22: 455-463 Crossref PubMed Scopus (104) Google Scholar ] and then we developed a non-invasive approach, low level tragus nerve stimulation (LL-TS), and found that it had the same effect on suppressing AF [ [5] Yu L. Scherlag B.J. Li S. Fan Y. Dyer J. Male S. Varma V. Sha Y. Stavrakis S. Po S.S. Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve: a noninvasive approach to treat the initial phase of atrial fibrillation. Heart Rhythm. 2013; 10: 428-435 Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar ]. However, whether LL-TS could regulate Cx40 and Cx43 to suppress AF remains unknown. We hypothesized that LL-TS exerted anti-atrial fibrillatory effect via the downregulation of atrial Cx40 and Cx43.

Cold Pressor Response in First M.B.B.S Students a Month Before Send-Up Examinations

Psychological stressors like examinations lead to stimulation of autonomic nervous system resulting in effects in heart, blood pressure, respiratory rate etc. Cold pressor test (CPT) is a validated test for sympathetic activity. The objective of the study was to study the sympathetic activity using CPT, 5 months prior and 1 month prior to send- up examination in first professional MBBS students. 90 first professional MBBS students (55 females, 35 males) in the age group of 18-22 years were subjected to CPT at two instances, 5 months before and 1 month before their send-up examinations. The collected data was statistically analysed. In male as well as female students, resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) did not show significant change both 5 months and 1 months prior to examinations. The value of both SBP and DBP after CPT in males showed a highly significant increase but while comparing the two time periods, the increase was not significant. The value of SBP and DBP in females increased significantly after CPT in both instances and while comparing the values, i.e, 5 months prior and 1 month prior to examinations, the increase was highly significant. There does occur increase in sympathetic activity in students who were to appear in their send up examination consequent to the psychological stress faced by them. This change was more evident in female subjects as compared to male subjects. This test can also be used as a screening test for hypertension amongst the subjects.

Acute electrophysiological modulation of the atria and pulmonary veins: Effects of sympathetic and parasympathetic interaction on atrial fibrillation inducibility

IntroductionAtrial fibrillation (AF) is a complex disease with multiple mechanisms, including the interaction with the autonomic nervous system (ANS), electrophysiological properties of the atria and pulmonary veins (PVs), and vulnerability for AF. We assessed the effects of acute vagal (vagus_stim) and sympathetic stimulation (symp_stim) on atrial conduction, atrial and PV refractoriness and inducibility of AF in an in vivo rabbit model with preserved autonomic innervation. MethodsAn open-epicardial approach was used in 17 anesthetized and artificially ventilated New Zealand white rabbits. The ECG was recorded with bipolar subcutaneous electrodes placed in the four limbs. Electrograms were obtained with four monopolar electrodes placed epicardially along the atria, and an electrode adapted to the proximal PVs. The cervical vagus nerve and thoracic sympathetic trunk were stimulated with bipolar electrodes. Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs) and conduction times from the high-lateral right atrium (RA) to the high-lateral left atrium (LA) and PVs were quantified at baseline and during vagus_stim, symp_stim, or combined vagal and sympathetic stimulation (dual_stim). Burst pacing (50Hz, 10s), alone or combined with vagus_stim, symp_stim or dual_stim, was performed in the right (RAA) and left atrial appendage (LAA) and PVs to test for AF inducibility. ResultsAt baseline, ERPs were higher in the LAA and there was a delay in the conduction time from RA to PV, compared to the mean activation time from RA to LA. During vagus_stim or dual_stim, ERP decreased significantly at all sites, and baseline interatrial activation times changed from 20±4ms to 30±10ms and from 21±5ms to 31±11ms, respectively (p<0.05). Symp_stim resulted in a significant decrease in ERPs only in the LAA, and a reduction of the interatrial interval to 16±11ms (p<0.05 vs. baseline). AF inducibility ranged from 35% to 53% with baseline 50Hz pacing, 65–76% during vagus_stim or symp_stim, and 75–100% with dual_stim (p<0.05). AF duration increased significantly during ANS stimulation. In two-thirds of the animals with longer inducible AF, the arrhythmia ceased immediately after cessation of vagus_stim. ConclusionsIn the fully innervated rabbit heart in vivo, acute ANS stimulation shortens atrial and PV refractoriness, and significantly changes atrial conduction times, promoting AF induction and prolonging the arrhythmia. This underscores the importance of acute variations in ANS tone and its interactions in the pathophysiology of AF.

Modulação eletrofisiológica das aurículas e veias pulmonares: interação da estimulação simpática e parassimpática na inducibilidade de fibrilhação aguda auricular num modelo experimental in vivo

Atrial fibrillation (AF) is a complex disease with multiple mechanisms, involving the interaction between the autonomic nervous system (ANS), electrophysiological properties of the atria and pulmonary veins (PVs), and vulnerability for AF. AimWe assessed the effects of acute vagal (vagus_stim) and sympathetic stimulation (symp_stim) on atrial conduction, atrial and PV refractoriness and inducibility of AF in an in vivo rabbit model with preserved autonomic innervation. MethodsAn open-epicardial approach was used in 17 anesthetized and artificially ventilated New Zealand white rabbits. The ECG was recorded with bipolar subcutaneous electrodes placed in the four limbs. Electrograms were obtained with four monopolar electrodes placed epicardially along the atria, and a circular electrode adapted to the proximal PVs. The cervical vagus nerve and thoracic sympathetic trunk were stimulated with bipolar electrodes. Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs) and conduction times from the high-lateral right atrium (RA) to the high-lateral left atrium (LA) and PVs were quantified at baseline and during vagus_stim, symp_stim, or combined vagal and sympathetic stimulation (dual_stim). Burst pacing (50Hz, 10s), alone or combined with vagus_stim, symp_stim or dual_stim, was performed in the right (RAA) and left atrial appendage (LAA) and PVs to test for AF inducibility. ResultsAt baseline, ERPs were higher in the LAA and there was a delay in the conduction time from RA to PV, compared to the mean activation time from RA to LA. During vagus_stim or dual_stim, ERP decreased significantly at all sites, and baseline interatrial activation times changed from 20±4ms to 30±10ms and 31±11ms, respectively (p<0.05). Symp_stim resulted in a significant decrease in ERPs only in the LAA, and a reduction of the interatrial interval to 16±11ms (p<0.05 vs baseline). AF inducibility ranged from 35% to 53% with baseline 50Hz pacing, 65% to 76% during vagus_stim or symp_stim, and 75% to 100% with dual_stim (p<0.05). AF duration increased significantly during ANS stimulation. In two-thirds of the animals with longer inducible AF, the arrhythmia ceased immediately after cessation of vagus_stim. ConclusionsIn the fully innervated rabbit heart in vivo, acute ANS stimulation shortens atrial and PV refractoriness, and significantly changes atrial conduction times, promoting AF induction and prolonging the arrhythmia. This underscores the importance of acute variations in ANS tone and its interactions in the pathophysiology of AF.

Effects of acute autonomic modulation on atrial conduction delay and local electrograms duration in paroxysmal atrial fibrillation

Slowed atrial conduction may contribute to reentry circuits and vulnerability for atrial fibrillation (AF). The autonomic nervous system (ANS) has modulating effects on electrophysiological properties. However, complex interactions of the ANS with the arrhythmogenic substrate make it difficult to understand the mechanisms underlying induction and maintenance of AF. Aim To determine the effect of acute ANS modulation in atrial activation times in patients (P) with paroxysmal AF (PAF). Methods and results 16P (9 men; 59 ± 14 years) with PAF, who underwent electrophysiological study before AF ablation, and 15P (7 men; 58 ± 11 years) with atrioventricular nodal reentry tachycardia, without documentation or induction of AF (control group). Each group included 7P with arterial hypertension but without underlying structural heart disease. The study was performed while off drugs. Multipolar catheters were placed at the high right atrium (HRA), right atrial appendage (RAA), coronary sinus (CS) and His bundle area (His). At baseline and with HRA pacing (600 ms, shortest propagated S2) we measured: i) intra-atrial conduction time (IACT, between RAA and atrial deflection in the distal His), ii) inter-atrial conduction time (interACT, between RAA and distal CS), iii) left atrial activation time (LAAT, between atrial deflection in the distal His and distal CS), iv) bipolar electrogram duration at four atrial sites (RAA, His, proximal and distal CS). In the PAF group, measurements were also determined during handgrip and carotid sinus massage (CSM), and after pharmacological blockade of the ANS (ANSB). AF was induced by HRA programmed stimulation in 56% (self-limited — 6; sustained — 3), 68.8% (self-limited — 6; sustained — 5), and 50% (self-limited — 5; sustained — 3) of the P, in basal, during ANS maneuvers, and after ANSB, respectively ( p = NS). IACT, interACT and LAAT significantly lengthened during HRA pacing in both groups (600 ms, S2). P with PAF have longer IACT ( p < 0.05), a higher increase in both IACT, interACT ( p < 0.01) and electrograms duration ( p < 0.05) with S2, and more fragmented activity, compared with the control group. Atrial conduction times and electrograms duration were not significantly changed during ANS stimulation. Nevertheless, ANS maneuvers increased heterogeneity of the local electrograms duration. Also, P with sustained AF showed longer interACT and LAAT during CSM. Conclusion Atrial conduction times, electrograms duration and fractionated activity are increased in PAF, suggesting a role for conduction delays in the arrhythmogenic substrate. Acute vagal stimulation is associated with prolonged interACT and LAAT in P with inducible sustained AF and ANS modulation may influence the heterogeneity of atrial electrograms duration.

Enhanced Cholinergic Response in Pancreata of Nonhuman Primates with Impaired Glucose Tolerance Shown on [18F]Fluorobenzyltrozamicol Positron Emission Tomography

Islet cell adaptation to insulin resistance in type 2 diabetes mellitus may be due in part to increased stimulation of beta cells by the autonomic nervous system. The parasympathetic neurotransmitter acetylcholine (ACh) mediates insulin release via M3 muscarinic receptors on islet beta cells. The vesicular ACh transporter (VAChT) receptor correlates with cholinergic activity in vivo. The positron emission tomography (PET) radiotracer (+)-4-[18F]fluorobenzyltrozamicol ([18F]FBT) binds to the VAChT receptor on presynaptic cholinergic neurons and can be quantified by PET. In this study, we utilize [18F]FBT PET to demonstrate pancreatic cholinergic activity before and after dextrose infusion in nonhuman primates with normal (NGT) and impaired (IGT) glucose tolerance. Seven adult female vervet (Chlorocebus aethiops) monkeys were maintained on an atherogenic Western diet. They were divided into two groups: four with NGT and three with IGT. Each subject underwent [18F]FBT PET twice: first, a baseline PET under fasting conditions; and second, PET under fasting conditions but after intravenous infusion of dextrose solution. Quantitative analysis of pancreatic uptake at 60 min post-injection was performed. There was no difference in pancreatic uptake of [18F]FBT on baseline scans between the two groups. Pancreatic uptake of [18F]FBT increased in every subject after dextrose infusion (P = 0.03). On post-dextrose PET scans, pancreatic uptake of [18F]FBT was significantly higher in IGT subjects compared with NGT subjects (P = 0.03). The post-dextrose to pre-dextrose uptake ratios were higher in IGT subjects (P = 0.08). Acute increases in pancreatic cholinergic activity in vivo were detected in the pancreata of nonhuman primates with NGT and IGT after intravenous dextrose infusion on [18F]FBT PET. In subjects with IGT, this activity was significantly higher, suggesting increased autonomic nervous system stimulation of the pancreatic islets in insulin-resistant subjects.

The expression and functional role of nicotinic acetylcholine receptors in rat adipocytes.

To clarify whether nicotine has a direct effect on the function of adipocytes, we evaluated nicotinic acetylcholine receptor (nAChR) expression in adipocytes by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry and the direct effects of nicotine on the production of adipocytokines by enzyme-linked immunosorbent assay and Western blot analysis. Receptor binding assays were performed using [3H]nicotine. RT-PCR studies revealed that alpha1-7, 9, 10, beta1-4, delta, and epsilon subunit mRNAs are expressed in adipocytes. Immunocytochemical experiments also suggested the presence of alpha7 and beta2 subunits. The receptor binding assay revealed a binding site for nicotine (Kd = 39.2 x 10(-9) M) on adipocytes. Adipocytes incubated with nicotine for 12 and 36 h released tumor necrosis factor-alpha (TNF-alpha), adiponectin, and free fatty acid (FFA) into the medium in a dose-dependent manner with increasing nicotine concentration from 6 x 10(-8) to 6 x 10(-4) M. However, TNF-alpha protein levels in adipocytes incubated for 12 and 36 h decreased in a dose-dependent manner with increasing nicotine concentration from 6 x 10(-8) to 6 x 10(-4) M. These results show that adipocytes have functional nAChRs and suggest that nicotine reduces TNF-alpha protein production in adipocytes through the activation of nAChRs. Nicotine may temporarily lower insulin sensitivity by stimulating the secretion of TNF-alpha and FFA, whereas long-term direct stimulation of nAChRs by nicotine in addition to autonomic nervous system stimulation may contribute to better insulin sensitivity in vivo through a modulated secretion of adipocytokines.

Abnormal blood pressure in prepubertal children with sleep-disordered breathing.

The purpose of this study was to investigate the association between low blood pressure (BP) with mild symptoms of orthostatism, sleep-disordered breathing (SDB) and tilt test results in 7- to 12-y-old children. A retrospective chart review of 301 children, ages 7 to 12 y, was initially performed to evaluate the frequency of abnormal BP measurements. Then a prospective study was performed on 7- to 12-y-old prepubertal children with SDB, looking for both abnormal BP and mild orthostatism. All children had polysomnography. Those identified with abnormal (high or low) BP measurements (called "BP outliers") were studied with a new polysomnogram followed by a head-up tilt test as an indicator of autonomic activity. Four of the children with low BP were treated with nasal continuous positive airway pressure and received a second head-up tilt test 3.5 to 7 mo after starting treatment. The prospective study included 78 children, eight of whom were BP outliers. Seven of these outliers had low BP. Compared with all of the SDB subjects, SDB subjects with low BP and indicators of mild orthostatic hypotension had a significantly higher incidence of craniofacial dysmorphism, symptoms of SDB early in life, chronically cold extremities, and dizziness on standing up (chi2, p = 0.01 to 0.0001). They had a significantly greater drop in BP without evidence of autonomic neuropathy than all other children on head-up tilt testing (Kruskal-Wallis ANOVA with Bonferroni adjustment, p = 0.001 to 0.0001). However, the normotensive SDB controls also had significantly different BP drops than the normal controls (p = 0.0001). The four children placed on nasal continuous positive airway pressure had a nonsignificant trend toward normalization of tilt test response. SDB in prepubertal children can lead to different abnormal stimulation of the autonomic nervous system, with different impacts on BP. The severity and frequency of oxygen saturation drops during sleep, nonhypoxic increases in respiratory effort, and the duration of abnormal breathing are suspected of playing a role in the difference in autonomic nervous system stimulation.

Anesthesia for electroconvulsive therapy.

Anesthesia for electroconvulsive therapy.

THE EFFECTS OF A PSYCHOLOGICAL PREPARATION PROGRAM ON ANXIETY IN CHILDREN AND ADOLESCENTS UNDERGOING GASTROINTESTINAL ENDOSCOPY

Purpose: To investigate the effects of a psychological preparation program prior to gastrointestinal endoscopy on: patient self-reported anxiety, parental self-reported anxiety, observed patient anxiety, patient autonomic nervous system stimulation and dosage of medication required for procedural sedation. Methods: Sixty patients ages 5-19 yrs (mean=12.2 yrs) were randomized into one of two groups. Group 1 received routine preparation prior to endoscopy. Group 2 received psychologic preparation provided by a Child Life Specialist. Preparation consisted of demonstration of materials that would be encountered during the procedure, use of a doll as a model or book with photographs of a child who had previously undergone endoscopy. Patients in both groups completed the Spielberger State Anxiety Inventory (STAI) at the time of their clinic appointment and just prior to endoscopy. The Observational Scale of Behavioral Distress was completed by the same blinded observer during each procedure. Vital signs were recorded in clinic and just prior to endoscopy. The attending physician (blinded) assessed patient cooperation. Parents and patients completed post-endoscopy questionnaires. Results: Analysis of the STAI showed patients in Group 2 were significantly less anxious prior to endoscopy (p<0.0001). They also required less mg/kg of meperidine (p=0.04) and were more cooperative during the exam (p=0.042). There was significantly less autonomic nervous system stimulation just prior to the procedure compared to baseline in patients who had undergone psychologic intervention (change in heart rate:p<0.001; change in systolic blood pressure: p=0.040). There was no significant difference between Group 1 and Group 2 with respect to observed behavioral distress during the procedure or mg/kg of midazolam administered. Statistically significant differences were found in the patients' response to post-endoscopy questions regarding perceived procedural anxiety (p=0.003) and the parents' response to questions regarding their own condition (p=0.026) and their children's (p<0.001). Conclusion: We conclude that psychological preparation prior to endoscopy significantly decreases patient and parental anxiety. Such preparation may allow for a reduction in sedative medications and thereby enhance procedural safety.

Anesthetic Considerations in Porphyrias

Anesthetic Considerations in Porphyrias

Gastric mucosal injury: microcirculation and Helicobacter pylori.

The integrity of gastric mucosa is well-balanced by an array of defensive mechanisms which protect the mucosa against external aggressive factors. When excessive stimulation of autonomic nervous system (irritation) is induced, microcirculatory disturbances easily lead to the gastric mucosal damage due to the formation of vasoactive mediators and oxygen radicals. In this review, our discussion has been focused on the co-ordinating function of the autonomic nervous system as well as the microcirculation as an important defense bastion. In this context, Helicobacter pylori represents an important pathogenic factor. In particular, we have discussed the contribution of monochloramine, and active oxidant, which is formed by neutrophils in the presence of ammonia derived from H. pylori to the gastric mucosal injury. Microcirculatory disturbances may be also involved in the pathogenesis of H. pylori-induced mucosal injury. On the basis of these considerations, we should not depend solely on the use of anti-acid secretory drugs for the treatment of gastric mucosal injury, but also should be aware of beneficial effect of mucosal protective drugs which may act on microcirculation and the autonomic nervous system.

Anesthetic considerations for electroconvulsive therapy.

Electrically induced seizures have been used widely to treat psychiatric disease since their introduction in 1938. Seizure activity is the therapeutic aspect of this form of treatment, but it is accompanied by untoward physiologic consequences. Cardiovascular responses consist of generalized autonomic nervous system stimulation with initial parasympathetic outflow, followed immediately by a sympathetic response. In certain patients the sequence described may result in an initial bradycardia or even asystole, followed by tachycardia, dysrhythmia, and hypertension. The cerebrovascular system responds with a marked increase in cerebral blood flow in response to increased cerebral oxygen consumption, and dramatic elevation of intracranial pressure. General anesthesia for electroconvulsive therapy (ECT) must be administered only in locations equipped for support of the unconscious patient and treatment of complications. Intravenous access is mandatory in all patients, as is monitoring of blood pressure, and ECG, as well as pulse oximetry. Appropriate oxygen supplementation and ventilatory support are essential as they are during any procedure necessitating general anesthesia. Methohexital, 0.75 to 1.0 mg/kg intravenously, is the most frequently used agent for induction of anesthesia for ECT; muscle relaxation usually is accomplished with succinylcholine, 0.5 to 1.0 mg/kg. In patients at risk for ill effects from the tachycardia and hypertension that may accompany sympathetic nervous system response to ECT, nitroglycerin, propranolol, hydralazine, or other sympatholytic agents should be used to attenuate the potentially harmful sequelae of ECT. The efficacy of ECT requires a knowledge of anesthetic precepts, an understanding of the interaction between anesthetic drugs and seizure activity, and an awareness of the physiologic effects of ECT as well as the treatment of those effects.