Vagal Blockade Research Articles

Intraduodenal nutrient infusion differentially alters intestinal nutrient sensing, appetite, and satiety responses in lean and obese subjects

BackgroundIntestinal nutrient sensing regulates food intake and energy metabolism by acting locally and relaying nutritional status to the brain. It is unclear whether these mechanisms are altered in obese humans. ObjectivesWe aimed to investigate differences in duodenal nutrient sensing in humans with or without obesity and the effects of transiently blocking vagal transmission on nutrient sensing, hunger, and appetite. MethodsIn a single-blinded, randomized, cross-over design, subjects with or without obesity (n = 14 and n = 11, respectively) were infused intraduodenally with saline or a combination of glucose and oleic acid for 90 min (glucose load: 22.5 g, 1 kcal/min; oleic acid load: 10 g, 1 kcal/min) in the presence or absence of local anesthetic (benzocaine). Blood was sampled at 10-min intervals (120–240 min) and 15-min intervals until termination of the study for measurements of gut hormones, insulin, leptin, and C-peptide. Hunger and satiety sensations were scored using the visual analog scale, and hepatic glucose production and glucose oxidation rates were measured. ResultsDuodenal nutrient infusion in lean subjects led to a 65% drop in acyl ghrelin release and robustly increased cholecystokinin 8 (CCK-8) release (65%; P = 0.023); benzocaine infusion delayed this response (2-factor repeated-measures analysis of variance, P = 0.0065). In contrast, subjects with obesity had significantly blunted response to nutrient infusion, and no further effects were observed with benzocaine. Additionally, significant delays were observed in peptide YY (3-36), pancreatic polypeptide, glucose inhibitory peptide, and glucagon-like peptide 1 (7-36) response. No significant interactions were found between body mass index (BMI) or baseline hormone levels and areas under the curve for hormones except CCK-8 (BMI, P = 0.018; baseline CCK, P = 0.013). Nutrient-induced hunger and satiety sensations were impeded by benzocaine only in the lean cohort. Hunger and satiety sensations in subjects with obesity were not responsive to nutrient entry into the duodenum, and no additional effects were observed by blocking neural signaling. ConclusionNutrient-induced gut hormone release and response to transient vagal blockade are significantly blunted in subjects with obesity.This trial was registered at clinicaltrials.org as NCT02537314.

Metabolic effects of truncal vagotomy when combined with bariatric-metabolic surgery

Bariatric-metabolic surgery (BMS) in patients with obesity frequently leads to remission of concurrent type 2 diabetes mellitus (T2DM), even before body weight loss takes place. This is probably based on the correction of a dysmetabolic cycle in the gastrointestinal physiology of T2DM that includes increased vagus-dependent exocrine pancreatic secretion (EPS) and, hence, amplified digestion and nutrient absorption. The resultant chronic exposure of tissues to high plasma levels of glucose, fatty acids and amino acids causes tissue resistance to the actions of insulin and, at a later stage, β-cell dysfunction and reduction of insulin release. We hypothesize that the addition of a surgical truncal vagotomy (TV) may improve and solidify the beneficial results of BMS on T2DM by stably decreasing EPS, − hence reducing the digestion and absorption of nutrients -, and increasing incretin secretion as a result of increased delivery of unabsorbed nutrients to the distal intestine. This hypothesis is supported by surgical data from gastrointestinal malignancies and peptic ulcer operations that include TV, as well as by vagal blockade studies. We suggest that TV may result in a stable reduction of EPS, and that its combination with the appropriate type of BΜS, may enhance and sustain the salutary effects of the latter on T2DM.

Vagal blockade suppresses the phase I heart rate response but not the phase I cardiac output response at exercise onset in humans

PurposeWe tested the vagal withdrawal concept for heart rate (HR) and cardiac output (CO) kinetics upon moderate exercise onset, by analysing the effects of vagal blockade on cardiovascular kinetics in humans. We hypothesized that, under atropine, the φ1 amplitude (A1) for HR would reduce to nil, whereas the A1 for CO would still be positive, due to the sudden increase in stroke volume (SV) at exercise onset.MethodsOn nine young non-smoking men, during 0–80 W exercise transients of 5-min duration on the cycle ergometer, preceded by 5-min rest, we continuously recorded HR, CO, SV and oxygen uptake ( dot{V} O2) upright and supine, in control condition and after full vagal blockade with atropine. Kinetics were analysed with the double exponential model, wherein we computed the amplitudes (A) and time constants (τ) of phase 1 (φ1) and phase 2 (φ2).ResultsIn atropine versus control, A1 for HR was strongly reduced and fell to 0 bpm in seven out of nine subjects for HR was practically suppressed by atropine in them. The A1 for CO was lower in atropine, but not reduced to nil. Thus, SV only determined A1 for CO in atropine. A2 did not differ between control and atropine. No effect on τ1 and τ2 was found. These patterns were independent of posture.ConclusionThe results are fully compatible with the tested hypothesis. They provide the first direct demonstration that vagal blockade, while suppressing HR φ1, did not affect φ1 of CO.

Cardiac vagal tone: a neurophysiological mechanism that evolved in mammals to dampen threat reactions and promote sociality.

Cardiac vagal tone: a neurophysiological mechanism that evolved in mammals to dampen threat reactions and promote sociality.

Leptin signaling in vagal afferent neurons supports the absorption and storage of nutrients from high-fat diet

Objective:Activation of vagal afferent neurons (VAN) by postprandial gastrointestinal signals terminates feeding and facilitates nutrient digestion and absorption. Leptin modulates responsiveness of VAN to meal-related gastrointestinal signals. Rodents with high-fat diet (HF) feeding develop leptin resistance that impairs responsiveness of VAN. We hypothesized that lack of leptin signaling in VAN reduces responses to meal-related signals, which in turn decreases absorption of nutrients and energy storage from high-fat, calorically dense food.Methods:Mice with conditional deletion of the leptin receptor from VAN (Nav1.8-Cre/LepRfl/fl; KO) were used in this study. Six-week-old male mice were fed a 45% HF for 4 weeks; metabolic phenotype, food intake, and energy expenditure were measured. Absorption and storage of nutrients were investigated in the refed state.Results:After 4 weeks of HF feeding, KO mice gained less body weight and fat mass that WT controls, but this was not due to differences in food intake or energy expenditure. KO mice had reduced expression of carbohydrate transporters and absorption of carbohydrate in the jejunum. KO mice had fewer hepatic lipid droplets and decreased expression of de novo lipogenesis-associated enzymes and lipoproteins for endogenous lipoprotein pathway in liver, suggesting decreased long-term storage of carbohydrate in KO mice.Conclusions:Impairment of leptin signaling in VAN reduces responsiveness to gastrointestinal signals, which reduces intestinal absorption of carbohydrates and de novo lipogenesis resulting in reduced long-term energy storage. This study reveals a novel role of vagal afferents to support digestion and energy storage that may contribute to the effectiveness of vagal blockade to induce weight loss.

Gastroesophageal reflux disease and atrial fibrillation: Insight from autonomic cardiogastric neural interaction.

The relationship between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF) has been previously reported. However, the detailed mechanism remains unknown. In this study, we investigated the effects of acid reflux on the intrinsic cardiac autonomic nervous system, atrial/ventricular electrophysiology, and AF inducibility. Eighteen rabbits were randomized into three groups: acid reflux (group 1, n = 6), control (group 2, n = 6), and acid reflux with periesophageal vagal blockade (group 3, n = 6). Atrial and ventricular effective refractory periods (ERPs) and AF inducibility were checked at baseline and then hourly until 5 hours after the experiment. Three hours after the experiment, atrial ERP prolongation was noted in groups 2 and 3 (P < .05), whereas shortening of the atrial ERPs was observed in group 1, compared with the baseline. However, no changes were observed in ventricular ERPs in the three groups. The AF inducibility was higher in group 1 than in groups 2 and 3. Pathological examination showed clear esophageal mucosal breaks in groups 1 and 3. In this study, we found that the antimuscarinic blockade prevents GERD induced changes to atrial electrophysiology and susceptibility to AF-making it highly likely that autonomic activity is important in mediating this effect.

Phase synchronization of baroreflex oscillations of blood pressure and pulse interval in rats: the effects of cardiac autonomic blockade and gradual blood loss

Objective: Phase synchronization of arterial pressure (AP) and pulse interval (PI) oscillations in the low-frequency band (around 0.4 Hz in rats) is governed by baroreflex activity. In long-term stationary data recordings, such synchronization can be estimated by the coherence. The phase synchronization index (PSI) can be used as well. The aim of this study was to correlate PSI and the coherence of AP and PI under stationary conditions and to estimate the informativity of PSI as a measure of baroreflex activity during transient processes. Approach: AP and PI were recorded in conscious Wistar rats using femoral artery catheters. To study the hemodynamics during hemorrhage, blood was gradually withdrawn (20 ml × kg−1 over 30 min) through a catheter in the carotid artery. Main results: PSI and coherence spectra calculated from 30-minute AP and PI recordings demonstrated distinct peaks at the frequency of 0.4 Hz; these indicators correlate well with each other (Pearson r = 0.920, p < 0.0001). Both PSI and coherence were markedly suppressed by vagal blockade (methylatropine) and tended to reduce after sympathetic blockade (atenolol). Importantly, PSI demonstrated dynamic alterations during gradual hemorrhage. During the initial approx. 10 min of hemorrhage, AP did not change but PI was noticeably shortened, and PSI increased, which indicates the activation of the baroreflex. With further blood loss, baroreflex influences were not enough to prevent blood pressure from falling, and under such conditions PSI decreased. Significance: PSI, like coherence, is an informative measure of baroreflex activity under stationary conditions. In addition, PSI permits us to follow the coupling between the baroreflex oscillations of AP and PI during transient processes, which strengthens its informative value.

Laparoscopic vagal nerve blocking device explantation: case series and report of operative technique.

Vagal nerve blockade with the vBloc device (ReShape Lifesciences, St. Paul, MN) has been shown to provide durable 2-year weight loss in patients with moderate obesity. These devices may require removal. We present a series of patients and report our technique for laparoscopic removal of this device. From December 2009 to December 2016, the medical records of patients who underwent laparoscopic explantation of a vagal blocking device at our institution were retrospectively reviewed. All patients initially underwent device placement as part of a multi-center, randomized, controlled trial. The device leads were removed with the application of firm traction in order to safely dissect them away from the stomach and esophagus as the body tended to form a fibrotic capsule surrounding the leads. Operative details, length of stay, 30-day post-operative complications, demographics and reasons for device removal were reported. Thirty patients were identified. Median age was 54 (37-65)years. Average operative time was 227.63 (± 100.21)min. Median time from implantation to removal was 41 (11-96)months. Removal reasons included device malfunction (7 patients, 23.3%), pain at the neuroregulator site (5 patients, 16.7%), retrosternal or epigastric pain (11 patients, 36.7%), weight regain or dissatisfaction with weight loss (15 patients, 50%), and severe nausea (2 patients, 6.7%). Two patients (6.7%) had Clavien-Dindo grade II complications following explantation. Thirteen patients (43.3%) had dense adhesions noted at the time of operation. Seroma formation at the neuroregulator site was the most common complication (7 patients, 23.3%). The vagal nerve blocking device can be safely removed laparoscopically with a low 30-day complication rate. Surgeons should be familiar with the details of the device appearance, the typical lead location, and should anticipate dense adhesions surrounding the leads. In addition, experience operating in the region of the gastroesophageal junction is imperative.

Nonintubated Uniportal Video-Assisted Thoracoscopic Surgery: A Single-Center Experience.

BackgroundWe report our surgical technique for nonintubated uniportal video-assisted thoracoscopic surgery (VATS) pulmonary resection and early postoperative outcomes at a single center.MethodsBetween January and July 2017, 40 consecutive patients underwent nonintubated uniportal VATS pulmonary resection. Multilevel intercostal nerve block was performed using local anesthesia in all patients, and an intrathoracic vagal blockade was performed in 35 patients (87.5%).ResultsTwenty-nine procedures (72.5%) were performed in patients with lung cancer (21 lobectomies, 6 segmentectomies, and 2 wedge resections), and 11 (27.5%) in patients with pulmonary metastases, benign lung disease, or pleural disease. The mean anesthesia time was 166.8 minutes, and the mean operative duration was 125.9 minutes. The mean postoperative chest tube duration was 3.2 days, and the mean hospital stay was 5.8 days. There were 3 conversions (7.5%) to intubation due to intraoperative hypoxemia and 1 conversion (2.5%) to multiportal VATS due to injury of the segmental artery. There were 7 complications (17.5%), including 3 cases of prolonged air leak, 2 cases of chylothorax, 1 case of pleural effusion, and 1 case of pneumonia. There was no in-hospital mortality.ConclusionNonintubated uniportal VATS appears to be a feasible and valid surgical option, depending on the surgeon’s experience, for appropriately selected patients.

Regulation of maternal-fetal heart rates and coupling in mice fetuses.

The aim of this preliminary study is to investigate if there is any evidence of maternal-fetal heart rate coupling in mice fetuses and how the coupling patterns are regulated by vagal nervous system on beat by beat. Total of 6 pregnant female mice were divided into two groups [control (N=3) and vagal blockade (N=3)]. On 17.5-day beat-to-beat heart rates of mothers and fetuses (MHR and FHR) were simultaneously measured for 20 minutes (10 minutes under normal condition and 10 minutes with saline (to control group) and atropine (to the vagal blockade group)) solution by using an invasive maternal and fetal electrocardiogram techniques with needle electrodes. Results show that occasional strong maternal-fetal heart rate coupling (strength was measured by $\lambda$) appeared and its patterns changed with atropine infusion (no change with saline). Additionally, fisher's exact test shows that changes (increase/decrease from pre to post injection values) in mean, rmssd and power spectral density (PSD) (2~4 Hz) of MHR, rmssd FHR and PSD (2~4 Hz) of${\lambda }$were found to be significantly (p<0.05) associated with treatment types (saline/ atropine). The presented results and protocol allow for the first time in the assessment of autonomic regulation of maternal and fetal heart and their interactions, which will further enhance the value of the mouse as a murine model of heritable human pregnancy and perinatal complications due to maternal conditions.

Influence of vagal control on sex-related differences in left ventricular mechanics and hemodynamics.

Left ventricular (LV) twist mechanics differ between men and women during acute physiological stress, which may be partly mediated by sex differences in autonomic control. While men appear to have greater adrenergic control of LV twist, the potential contribution of vagal modulation to sex differences in LV twist remains unknown. Therefore, the present study examined the role of vagal control on sex differences in LV twist during graded lower body negative pressure (LBNP) and supine cycling. On two separate visits, LV mechanics were assessed using two-dimensional speckle-tracking echocardiography in 18 men (22 ± 2 yr) and 17 women (21 ± 4 yr) during -40- and -60-mmHg LBNP and 25% and 50% of peak supine cycling workload with and without glycopyrrolate (vagal blockade). LV twist was not different at baseline but was greater in women during -60 mmHg in both control (women: 16.0 ± 3.4° and men: 12.9 ± 2.3°, P = 0.004) and glycopyrrolate trials (women: 17.7 ± 5.9° and men: 13.9 ± 3.3°, P < 0.001) due to greater apical rotation during control (women: 11.9 ± 3.6° and men: 7.8 ± 1.5°, P < 0.001) and glycopyrrolate (women: 11.6 ± 4.9° and men: 7.1 ± 3.6°, P = 0.009). These sex differences in LV twist consistently coincided with a greater LV sphericity index (i.e., ellipsoid geometry) in women compared with men. In contrast, LV twist did not differ between the sexes during exercise with or without glycopyrrolate. In conclusion, women have augmented LV twist compared with men during large reductions to preload, even during vagal blockade. As such, differences in vagal control do not appear to contribute to sex differences in the LV twist responses to physiological stress, but they may be related to differences in ventricular geometry. NEW & NOTEWORTHY This is the first study to specifically examine the role of vagal autonomic control on sex-related differences in left ventricular (LV) mechanics. Contrary to our hypothesis, vagal control does not appear to primarily determine sex differences in LV mechanical or hemodynamic responses to acute physiological stress. Instead, differences in LV geometry may be a more important contributor to sex differences in LV mechanics.

Role of the vagus nerve in the development and treatment of diet-induced obesity.

This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie-rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high-fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade-induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity.

Video-assisted thoracoscopic surgery segmentectomy by non-intubated or intubated anesthesia: a comparative analysis of short-term outcome.

The aim of this study was to reveal the short-term outcomes of video-assisted thoracoscopic surgery (VATS) segmentectomy without tracheal intubation compared with intubated general anesthesia with one-lung ventilation (OLV). We performed a retrospective review of our institutional database of consecutive 140 patients undergoing VATS anatomical segmentectomy from July 2011 to June 2015. Among them, 48 patients were treated without tracheal intubation using a combination of thoracic epidural anesthesia (TEA), intrathoracic vagal blockade, and sedation (non-intubated group). The other 92 patients were treated with intubated general anesthesia (intubated group). Safety and feasibility was evaluated by comparing the perioperative profiles and short-term outcomes of these two groups. Two groups had comparable surgical durations, intraoperative blood loss, postoperative chest tube drainage volume, and numbers of dissected lymph nodes (P>0.05). Patients who underwent non-intubated segmentectomy had higher peak end-tidal carbon dioxide (EtCO2) during operation (44.81 vs. 33.15 mmHg, P<0.001), less white blood cell changes before and after surgery (△WBC) (6.08×10(9) vs. 7.75×10(9), P=0.004), earlier resumption of oral intake (6.76 vs. 17.58 hours, P<0.001), shorter duration of postoperative chest tube drainage (2.25 vs. 3.16 days, P=0.047), less cost of anesthesia (¥5,757.19 vs. ¥7,401.85, P<0.001), and a trend toward shorter postoperative hospital stay (6.04 vs. 7.83 days, P=0.057). One patient (2.1%) in the non-intubated group required conversion to intubated OLV since a significant mediastinal movement. In the intubated group, there was one patient (1.1%) required conversion to thoracotomy due to uncontrolled bleeding. The incidence difference of postoperative complications between groups was not significant (P=0.248). There was no in-hospital death in either group. Compared with intubated general anesthesia, non-intubated thoracoscopic segmentectomy is a safe, technically feasible and economical alternative with comparable short-term outcomes. Patients underwent non-intubated thoracoscopic segmentectomy could gain a prompt recovery.

Limits of permutation-based entropies in assessing complexity of short heart period variability

The study compares permutation-based and coarse-grained entropy approaches for the assessment of complexity of short heart period (HP) variability recordings. Shannon permutation entropy (SPE) and conditional permutation entropy (CPE) are computed as examples of permutation-based entropies, while the k-nearest neighbor conditional entropy (KNNCE) is calculated as an example of coarse-grained conditional entropy. SPE, CPE and KNNCE were applied to ad-hoc simulated autoregressive processes corrupted by increasing amounts of broad band noise and to real HP variability series recorded after complete vagal blockade obtained via administration of a high dose of atropine (AT) in nine healthy volunteers and during orthostatic challenge induced by 90° head-up tilt (T90) in 15 healthy individuals. Over the simulated series the performances of SPE and CPE degraded more rapidly with the amplitude of the superimposed broad band noise than those of KNNCE. Over real data KNNCE identified the expected decrease of the HP variability complexity both after AT and during T90. Conversely SPE and CPE detected the decrease of HP variability complexity solely during T90 as a likely result of the more favorable signal-to-noise ratio during T90 than after AT. Results derived from both simulations and real data indicated that permutation-based entropies had a larger susceptibility to broad band noise than KNNCE. We recommend caution in applying permutation-based entropies in presence of short HP variability series characterized by a low signal-to-noise ratio.

Intra-Abdominal Vagal Nerve Blockade Doesn't Result in Substantial Weight Loss

In the continuing search for effective approaches to weight loss, vagal nerve blockade has been explored because of this nerve's influence on satiety. A subgroup analysis in a recent study suggested that blockade ≥12 hours daily was effective (Obes Surg 2012; 22:1771). In a new U.S. and Australian study, researchers …

Increased cardiac output, not pulmonary artery systolic pressure, increases intrapulmonary shunt in healthy humans breathing room air and 40% O2.

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) has been demonstrated to increase in healthy humans during a variety of conditions; however, whether or not this blood flow represents a source of venous admixture (Q̇ VA /Q̇T) that impairs pulmonary gas exchange efficiency (i.e. increases the alveolar-to-arterial PO2 difference (A-aDO2)) remains controversial and unknown. We hypothesized that blood flow through IPAVAs does provide a source of Q̇ VA /Q̇T. To test this, blood flow through IPAVAs was increased in healthy humans at rest breathing room air and 40% O2: (1) during intravenous adrenaline (epinephrine) infusion at 320ngkg(-1)min(-1) (320ADR), and (2) with vagal blockade (2mg atropine), before and during intravenous adrenaline infusion at 80ngkg(-1)min(-1) (ATR+80ADR). When breathing room air the A-aDO2 increased by 6±2mmHg during 320ADR and by 5±2mmHg during ATR+80ADR, and the change in calculated Q̇ VA /Q̇T was +2% in both conditions. When breathing 40% O2, which minimizes contributions from diffusion limitation and alveolar ventilation-to-perfusion inequality, the A-aDO2 increased by 12±7mmHg during 320ADR, and by 9±6mmHg during ATR+80ADR, and the change in calculated Q̇ VA /Q̇T was +2% in both conditions. During 320ADR cardiac output (Q̇T) and pulmonary artery systolic pressure (PASP) were significantly increased; however, during ATR+80ADR only Q̇T was significantly increased, yet blood flow through IPAVAs as detected with saline contrast echocardiography was not different between conditions. Accordingly, we suggest that blood flow through IPAVAs provides a source of intrapulmonary shunt, and is mediated primarily by increases in Q̇T rather than PASP.

Abraham Guz (1929-2014).

How do you describe a giant? As a person of abnormally great stature; above the usual size; or someone with much greater powers than the average person? Abraham Guz (‘Abe’) was not a tall man, but he was a scientific giant with an absolute desire to understand and find the scientific truth. This drive led him to make many original contributions in respiratory and cardiovascular physiology. Indeed, a simple literature search produces over 250 peer reviewed papers spanning some 50 years, the top 25 of which have been quoted over 2500 times. Moreover, most of his outstanding work was published in The Journal of Physiology, and we received it with gratitude because it was always insightful and ahead of its time. Many will argue that counting citations is a poor measure of scientific endeavour and I suspect Abe himself would certainly agree. However, this approach did provide us with a place to start when faced with the task of bringing together Abe's huge and varied scientific contributions.

The effect of vagal nerve blockade using electrical impulses on glucose metabolism in nondiabetic subjects.

PurposeVagal interruption causes weight loss in humans and decreases endogenous glucose production in animals. However, it is unknown if this is due to a direct effect on glucose metabolism. We sought to determine if vagal blockade using electrical impulses alters glucose metabolism in humans.Patients and methodsWe utilized a randomized, cross-over study design where participants were studied after 2 weeks of activation or inactivation of vagal nerve blockade (VNB). Seven obese subjects with impaired fasting glucose previously enrolled in a long-term study to examine the effect of VNB on weight took part. We used a standardized triple-tracer mixed meal to enable measurement of the rate of meal appearance, endogenous glucose production, and glucose disappearance. The 550 kcal meal was also labeled with 111In-diethylene triamine pentaacetic acid (DTPA) to measure gastrointestinal transit. Insulin action and β-cell responsivity indices were estimated using the minimal model.ResultsIntegrated glucose, insulin, and glucagon concentrations did not differ between study days. This was also reflected in a lack of effect on β-cell responsivity and insulin action. Furthermore, fasting and postprandial endogenous glucose production, integrated meal appearance, and glucose disposal did not differ in the presence or absence of VNB. Similarly, gastric emptying and colonic transit were unchanged by VNB.ConclusionIn this pilot study in nondiabetic humans, electrical vagal blockade had no acute effects on glucose metabolism, insulin secretion and action, or gastric emptying. It remains to be determined if more pronounced effects would be observed in diabetic subjects.

Oxidative stress and autonomic dysregulation contribute to the acute time-dependent myocardial depressant effect of ethanol in conscious female rats.

The molecular mechanisms of the acute hypotensive and indirectly assessed cardiac depressant effect of ethanol (EtOH)-evoked myocardial depression and hypotension in female rats are not known. We tested the hypothesis that a time-dependent myocardial depression caused by EtOH is initiated by its direct and indirect (cardiac vagal dominance) effects and is exacerbated by gradual development of oxidative stress. In conscious female rats, we directly measured left ventricular developed pressure (LVDP), the maximal rise of ventricular pressure over time (dP/dtmax ), blood pressure (BP), heart rate (HR), and sympathovagal activity following intragastric EtOH (1 g/kg) or water over 90 minutes. Catalytic activity of acetaldehyde (ACA)-generating (alcohol dehydrogenase [ADH] and catalase) and eliminating aldehyde dehydrogenase [ALDH2] enzymes along with mediators of oxidative stress were measured in myocardial tissues collected at 30, 60, or 90 minutes after EtOH or water. EtOH reduced myocardial function (LVDP and dP/dtmax ) within 5 to 10 minutes before the steady fall in BP in conscious proestrus rats. Further, EtOH shifted the sympathovagal balance, analyzed by spectral analysis of high frequency and low frequency of interbeat intervals, toward vagal dominance. Prior vagal blockade (atropine) or antioxidant (tempol) treatment attenuated EtOH-evoked myocardial depression and hypotension. Ex vivo studies revealed time-dependent: (i) enhancement of ADH, but not ALDH2 activity (indicative of elevated ACA levels), (ii) increases in phosphorylated Akt and ERK1/2, NADPH-oxidase activity, reactive oxygen species, malondialdehyde, and 4-hydroxy-2-nonenal-modified proteins. These molecular responses along with reduced myocardial catalase activity were most evident at 90 minutes post-EtOH when the reductions in cardiac function and BP reached their nadir. Vagal dominance and time-dependent myocardial oxidative stress along with the accumulation of cardiotoxic aldehydes mediate EtOH-evoked myocardial dysfunction and hypotension in conscious proestrus female rats.

Nonintubated thoracoscopic segmentectomy-left upper lobe trisegmentectomy.

Enhanced computed tomography screening protocols have recently identified increasing numbers of small lung tumors in patients with high surgical risks (1). Consequently there has been increasing interest in minimally invasive surgical approaches, including thoracoscopic approaches, parenchyma-sparing resection, and less invasive anesthesia for management of lung tumors (2). The role of thoracoscopic segmentectomy is therefore increasingly reevaluated, not only as a traditional parenchyma-sparing procedure in high-risk patients with compromised medical conditions but also in patients with non-small cell lung cancer less than 2.0 cm (1). From 2009, we started a nonintubated thoracoscopic surgery program for patients who were reluctant or unsuitable to have a conventional intubated single lung ventilation during thoracic surgery (3). With a combination of target-controlled sedation and regional anesthesia—either by thoracic epidural anesthesia or intercostal nerve blocks with intrathoracic vagal blockade—the results of nonintubated thoracoscopic surgery are encouraging (2-5). In the current video, we demonstrate how a nonintubated technique was applied in thoracoscopic segmentectomy and mediastinal lymphadenectomy to treat a patient with early stage lung cancer (Video 1). Video 1 Nonintubated thoracoscopic segmentectomy—left upper lobe trisegmentectomy. Clinical vignette A 74-year-old man, who had undergone a total gastrectomy for gastric cancer in a different institution in 2003, was transferred to our hospital for management of an incidentally discovered left upper lobe lung nodule. Computed tomography-guided biopsy of the tumor revealed a primary pulmonary adenocarcinoma. Preoperative pulmonary function tests showed that he had a mild obstructive defect with forced expiratory volume in one second being 84.9% of predicted. Considering his age and reduced lung function, lingual-preserving left upper lobectomy (left upper lobe tri-segmentectomy) was planned instead of left upper lobectomy to preserve more lung parenchyma after surgery.