Min Period Research Articles

Transcutaneous vagal nerve stimulation during lower body negative pressure

BackgroundPara-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular branch of the vagus nerve would attenuate the normal sympathetic response to central blood volume reduction by lower body negative pressure (LBNP). Method10 healthy volunteers (6 female; age 21 ± 2 years; weight 62 ± 13 kg; height 167 ± 12 cm) were included in this cross-over design trial. After 15 min rest in supine position, subjects underwent three 15-min periods of 30 mmHg LBNP intervention with and without cyclic tVNS stimulation. Continuous cardiovascular parameters (Nexfin) were recorded. ResultsOverall tVNS did not convincingly attenuate sympathetic response to central hypovolemia. Deactivation of the tVNS during LBNP resulted in increased MAP at 2.3 ± 0.5 mmHg (P < 0.001). Comparing the cyclic actual active stimulation periods to periods with pause during tVNS intervention showed a decrease in HR by 72.9 ± 11.2 to 70.2 ± 11.6 bpm (mean ± SD; P < 0.05), and concomitant increases in SV (86.0 ± 12.1 to 87.2 ± 12.6 mL; P < 0.05), MAP (82.9 ± 6.3 to 84.0 ± 6.2 mmHg; P < 0.05) and TPR (1116.0 ± 111.1 to 1153 ± 104.8 dyn*s/cm5; P < 0.05). ConclusiontVNS in 30 s cycles during LBNP can selectively attenuate HR, prompting a compensatory augmented sympathetic response. It would appear the method used in this study at least, has an isolated cardiac inhibitory effect probably mediated by augmented vagal activity on the sinoatrial or atrio-ventricular node, possibly in combination with reduced activity in the sympathetic cardiac nerve.

Transcranial magnetic stimulation in the assessment of acupuncture effect on exercise-induced fatigue.

Acupuncture as a traditional Chinese medicine therapy relies on unique theories to alleviate fatigue. The aim of this study is to evaluate the effect of acupuncture on exercise-induced fatigue utilizing transcranial magnetic stimulation (TMS). A total of 20 participants with regular exercise habits were recruited for this study. All participants were randomly assigned to receive either acupuncture or sham acupuncture intervention for exercise-induced fatigue. TMS and a heart rate monitor were used to measure the amplitude and latency of motor evoked potential (MEP) as well as heart rate every 5min over a 30-min period. The blood lactic acid (BLA) levels were measured using Lactate Scout+ at baseline, 0min, and 30min after fatigue. Two-way repeated measures analysis of variance was utilized to compare the differences between the effects of acupuncture method and time. Bonferroni post hoc tests were conducted to compare specific differences. Statistical significance was set at p<.05. Interaction effect was observed between acupuncture method and time effect in terms of amplitude (F(1, 38)=5.40, p<.001, η2=0.12) and latency (F(1, 38)=3.78, p=.008, η2=.09) of MEP. The application of acupuncture can promote the recovery of heart rate especially at 30min (p<.05), but which seem insufficient to generate significant difference in BLA (F(1, 38)=0.067, p=.797, η2=0.002). Acupuncture can promote the increase of MEP amplitude, shorten MEP latency, and restore heart rate. Preliminary findings provide novel insights for individuals with exercise habits to alleviate fatigue and enhance sports performance.

Atmospheric and Ionospheric Responses to Orographic Gravity Waves Prior to the December 2022 Cold Air Outbreak

AbstractMountain waves are known sources of fluctuations in the upper atmosphere. However, their effects over the Continental United States (CONUS) are considered modest as compared to hot spots such as the Southern Andes. Here, we present an observation‐guided case study examining the dynamics of gravity waves (GWs) and their impacts on the ionosphere over the CONUS prior to the cold air outbreak in December 2022, which resulted from a significant distortion of the tropospheric polar vortex. The investigation relies on MERRA‐2 and ERA5 reanalysis data sets for the climatological contextualization, analysis of GWs based on National Aeronautics and Space Administration Aqua satellite's Atmospheric Infrared Sounder, 557.7 and 630.0 nm airglow emission observations, and the measurements of ionospheric disturbances retrieved from Global Navigation Satellite System signal‐based total electron content (TEC) and Super Dual Auroral Radar Network observations. We demonstrate that the tropospheric polar jet stream shifted toward the Rocky Mountains, generated large amplitude GWs (up to 11 K of brightness temperature), which, aided by winter‐time winds over mid‐latitudes, could propagate to mesospheric heights. The breaking of GWs plausibly led to the generation of a plethora of secondary acoustic and GWs that eventually emerged as the sources of extensive ionospheric fluctuations of ∼3–30 min periods and up to 0.7 TECu, observed across the entire CONUS for several days. This case offers a valuable demonstration of the interplay between tropospheric circulation and the ionosphere over CONUS, pointing to the need for a better understanding of wave‐driven deep‐atmosphere coupled dynamics.

Three-dimensional crosslinked structure assembled by novel elemental iodine doped Nb2O5 ultrathin nanosheets for exceptional visible-light photocatalytic performance

The application of Nb2O5 in photocatalysis has sparked interest due to its potent oxidation capabilities and eco-friendly properties. However, challenges such as poor visible light response, limited reactive active sites and rapid charge recombination still hinder its practical use. Herein, a novel approach introduces elemental I-doped Nb2O5 (INO) catalyst with a three-dimensional crosslinked structure formed by ultrathin nanosheets, for the first time. This pioneering approach results in the INO catalyst with a high specific surface area (98.51 m2 g−1), abundant active sites, and enhanced visible light absorption. The dispersion of elemental I within the Nb2O5 lattice promotes the presence of delocalized electrons and improves charge carrier mobility, leading to superior catalytic performance for the degradation of diclofenac (DCF). During a 75-min period, the degradation efficiency of INO catalyst to diclofenac was found to reach 91.5 %, with a corresponding rate constant of 35.0 × 10−3 min−1. Furthermore, the study investigates the DCF degradation pathway and the toxicity changes in its byproducts. This innovative research opens new avenues for enhancing the visible light catalytic activity of Nb2O5 catalysts.

Observations of airflow around a supertall curved building and its impact on temperature and humidity in Houston's urban center

Characterization of realistically shaped skyscrapers embedded in non-uniform neighbourhoods experiencing intricate weather patterns remains inadequately investigated. Aiming to close this gap, the Center for Multiscale Applied Sensing team deployed its mobile observatory in the street canyons around the curved Wells Fargo Plaza skyscraper in downtown Houston, TX. Three deployments allowed airflow observations under different inflow wind and thermodynamic stability conditions. Doppler lidar measurements reveal that when inflow hits the curved wall of the skyscraper, perpendicular canyons experience similar vortex configurations creating two windward and two leeward circulations. Windsond measurements support that buoyancy within the deep street canyons can generate thermal updrafts as strong as 2 m s−1 which is sufficient to overturn the mechanical downwash under gentle wind conditions. Canyons experiencing venting during the daytime were observed to be more thermodynamically stable at night while thermodynamically stable canyons during the day were observed to be more thermodynamically unstable at night owing to the accumulation of heat near street-level. Fourier decomposition of the vertical velocity measurements shows that in all cases flow exhibited high Reynolds numbers and was composed of turbulent eddies of predominantly 6 and 15 min periods. This observational dataset provides insights to assess wind load, pedestrian comfort, urban air mobility, and natural ventilation and may be used as a benchmark for numerical model and wind tunnel studies attempting to represent realistically complex urban conditions.

PET Imaging of Neurofibromatosis Type 1 with a Fluorine-18 Labeled Tryptophan Radiotracer.

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[18F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[18F]FETrp had a comparable tumor uptake with [1⁸F]fluorodeoxyglucose (FDG). However, L-[18F]FETrp showed a significantly higher tumor-to-brain ratio than FDG (n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[18F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan-kynurenine pathway as a therapeutic target for treating NF1.

Quantification of saccadic fatigability and diagnostic efficacy for myasthenia gravis.

The diagnostic challenge of myasthenia gravis (MG) is exacerbated by the variable efficacy of current testing methodologies, necessitating innovative approaches to accurately identify the condition. This study aimed to assess ocular muscle fatigue in patients with MG using video-oculography (VOG) by examining repetitive saccadic eye movements and comparing these metrics to those of healthy control participants. This prospective, cross-sectional study was conducted at a tertiary care center and involved 62 patients diagnosed with MG (48 with ocular MG and 14 with generalized MG) and a control group of 31 healthy individuals, matched for age and sex. The assessment involved recording saccadic eye movements within a ± 15° range, both horizontally and vertically, at a rate of 15 saccades per minute over a 5-min period, resulting in 75 cycles. Participants were afforded a 3-min rest interval between each set to mitigate cumulative fatigue. The primary outcome was the detection of oculomotor fatigue, assessed through changes in saccadic waveforms, range, peak velocity, latency, and the duration from onset to target, with a focus on comparing the second saccade against the average of the last five saccades. In the evaluation of repetitive saccadic movements, patients with MG exhibited a reduced saccadic range and a prolonged duration to reach the target, compared to healthy subjects. Furthermore, a significant elevation in the frequency of multistep saccades was observed among MG patients, with a marked rise observed over consecutive trials. Receiver operating characteristic (ROC) analysis revealed the discriminative performance of multistep saccade frequency, in conjunction with variations in saccadic range and duration from onset to target achievement between the second saccade and the mean of the final five saccades, as effective in distinguishing MG patients from healthy subjects. Although alterations in peak saccadic velocity and latency were less pronounced, they were nevertheless detectable. The utilization of VOG for repetitive saccadic testing in the diagnosis of MG has demonstrated considerable diagnostic precision. This methodology affords significant accuracy in evaluating ocular muscle fatigue in MG patients, providing class III evidence supportive of its clinical application.

Optimizing Resuscitation of the Donation after Circulatory Death Heart by Mitochondrial Protection in a Female Porcine Model.

Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death [DCD]). Using a translational porcine model of DCD, this study developed and evaluated a protocol based on cardioprotection by multidrug postconditioning to optimize resuscitation of DCD hearts during ex situ heart perfusion (ESHP). Hearts of female pigs (45.0 ± 4.5 kg) were procured following a clinically identical DCD protocol, consisting of the termination of ventilator support and confirmation of circulatory arrest, followed by a 15-min standoff period. DCD hearts were randomly allocated to ESHP (38.4°C) in the absence (untreated, N = 5) or presence (treated, N = 5) of a postconditioning treatment added to the perfusate, consisting of Intralipid (1%), sevoflurane (2% v/v), and remifentanil (3 nM). All hearts were perfused with blood and Krebs-Henseleit solution (1:1) for 60 min in Langendorff mode and for an additional 300 min in working mode for a total perfusion time of 6 h. Oxidative capacity and detailed left ventricular mechanical function under an increasing workload (left atrial pressure, 6 to 12 mmHg) were assessed hourly. Left ventricular tissue was snap-frozen at the end of ESHP and used for molecular analyses. Left ventricular inotropy (LVdP/dtmax) did not decline over time in treated DCD hearts and was significantly higher at the end of the protocol as compared with untreated DCD hearts (ΔLVdP/dtmax = 440 mmHg/s; P = 0.009). Treated DCD hearts exhibited persistently higher left ventricular stroke work index during the 6-h period of ESHP, whereas untreated DCD hearts displayed a significant decline (change in left ventricular stroke work index = -3.10 ml · mmHg/g; P(time within untreated group) < 0.001). Treated DCD hearts displayed higher metabolic activity as measured by oxygen consumption (ΔO2 = 3.11 ml O2 · min-1 · 100 g-1; P = 0.004) and released lower amounts of cell-free mitochondrial DNA into the perfusate, a marker of potential graft dysfunction. Treated hearts also used fatty acids from Intralipid as an energy source, whereas untreated DCD hearts showed glyceroneogenesis with triglyceride accumulation and depletion of tricarboxylic acid cycle intermediates; reduced mitochondrial complex I, II, and III activities with accumulation of mitochondrial NADH, and signs of ultrastructural damage. A translationally relevant protective ESHP protocol consisting of treatment with Intralipid, sevoflurane, and remifentanil markedly accelerated functional recovery and improved viability of DCD hearts.

Dual role of ‘Al’ impregnated porous MCM-41/ZSM5 composites for the production of biohydrogen and green liquid hydrocarbons

Bio alternative fuels is the most researched concept due to the exhausting fossils and aggregating pollutants. Fuels of liquid and gaseous types are much in demand due to the high expectations from liquid and gas dependent engines. This report is the first of its kind to establish the effectiveness of the synthesized synergistic composite material of micro and mesoporosity for the simultaneous production of biohydrogen and bioliquid organics from kitchen waste. Optimization of temperature, feed:catalyst ratio, and time of study were studied using AlMCM-41 catalyst. Significant yield of products was obtained at 400 0C, 0.5 g of catalyst and at 40 min period. Core -shell type of composites were synthesized using AlMCM-41 and ZSM-5 zeolite with mesopores and micropores as shell and core respectively. The synthesized materials were characterized using XRD, BET, N2 sorption studies, TPD, SEM and TEM techniques. Composite AlMCM-41/ZSM-5 yielded the highest of 70% GLF and maximum of 26.5% of H2. The synergism was well established and also the catalysts showed remarkable reproducibility.

Cold atmospheric plasma enhances morphological and biochemical attributes of tomato seedlings

Cold atmospheric plasma (CAP) is a physical technology with notable effects on living organisms. In the present study, tomato seeds (Solanum lycopersicum var. Bassimo Mill.) were exposed to CAP for various time intervals, ranging from 1 to 5 min, in both continuous and intermittent periods, and were compared with a control group that received no CAP treatment. Seedlings grown from treated seeds exhibited improvements in levels of growth traits, photosynthetic pigments, and metabolite contents when compared to the control group. Seedlings from seeds treated with S04 displayed significant increases in shoot and root lengths, by 32.45% and 20.60% respectively, compared to the control group. Moreover, seedlings from seeds treated with S01 showed a 101.90% increase in total protein, whereas those treated with S02 experienced a 119.52% increase in carbohydrate content. These findings highlight the substantial improvements in growth characteristics, photosynthetic pigments, and metabolite levels in seedlings from treated seeds relative to controls. Total antioxidant capacity was boosted by CAP exposure. The activities of enzymes including superoxide dismutase, catalase, and peroxidases were stimulated by S02 and exceeded control treatment by (177.48%, 137.41%, and 103.32%), respectively. Additionally, exposure to S04 increased the levels of non-enzymatic antioxidants like flavonoids, phenolics, saponins, and tannins over the control group (38.08%, 30.10%, 117.19%, and 94.44%), respectively. Our results indicate that CAP-seed priming is an innovative and cost-effective approach to enhance the growth, bioactive components, and yield of tomato seedlings.

HiPSC-CM electrophysiology: impact of temporal changes and study parameters on experimental reproducibility.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are frequently used for preclinical cardiotoxicity testing and remain an important tool for confirming model-based predictions of drug effects in accordance with the comprehensive in vitro proarrhythmia assay (CiPA). Despite the considerable benefits hiPSC-CMs provide, concerns surrounding experimental reproducibility have emerged. We investigated the effects of temporal changes and experimental parameters on hiPSC-CM electrophysiology. iCell cardiomyocytes2 were cultured and biosignals were acquired using a microelectrode array (MEA) system (2-14 days). Continuous recordings revealed a 22.6% increase in the beating rate and 7.7% decrease in the field potential duration (FPD) during a 20-min equilibration period. Location-specific differences across a multiwell plate were also observed, with iCell cardiomyocytes2 in the outer rows beating 8.8 beats/min faster than the inner rows. Cardiac endpoints were also impacted by cell culture duration; from 2 to 14 days, the beating rate decreased (-12.7 beats/min), FPD lengthened (+257 ms), and spike amplitude increased (+3.3 mV). Cell culture duration (4-10 days) also impacted cardiomyocyte drug responsiveness (E-4031, nifedipine, isoproterenol). qRT-PCR results suggest that daily variations in cardiac metrics may be linked to the continued maturation of hiPSC-CMs in culture (2-30 days). Daily experiments were also repeated using a second cell line (Cor.4U). Collectively, our study highlights multiple sources of variability to consider and address when performing hiPSC-CM MEA studies. To improve reproducibility and data interpretation, MEA-based studies should establish a standardized protocol and report key experimental conditions (e.g., cell line, culture time, equilibration time, electrical stimulation settings, and raw data values).NEW & NOTEWORTHY We demonstrate that iCell cardiomyocytes2 electrophysiology measurements are impacted by deviations in experimental techniques including electrical stimulation protocols, equilibration time, well-to-well variability, and length of hiPSC-CM culture. Furthermore, our results indicate that hiPSC-CM drug responsiveness changes within the first 2 wk following defrost.

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care.

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

Low-dose short infusion ketamine as adjunct to morphine for acute long bone fracture in the emergency department: a randomized controlled trial

BackgroundKetamine is recognized as an alternative for pain management; however, concerns about emergent adverse reactions have limited its widespread adoption. This study aimed to assess the efficacy of a short infusion of low-dose ketamine (LDK) compared to intravenous morphine (MOR) as adjunctive analgesia for acute long bone fracture pain.MethodsThis single-blinded, randomized controlled trial was conducted in a single emergency department. Patients with acute long bone fractures and numerical rating scale (NRS) pain scores ≥ 6 following an initial dose of intravenous morphine were assigned to receive either a LDK (0.3 mg/kg) over 15 min or intravenous MOR at a dose of 0.1 mg/kg administered over 5 min. Throughout a 120-min observation period, patients were regularly evaluated for pain level (0–10), side effects, and the need for additional rescue analgesia.ResultsA total of 58 subjects participated, with 27 in the MOR group and 31 in the LDK group. Demographic variables and baseline NRS scores were comparable between the MOR (8.3 ± 1.3) and LDK (8.9 ± 1.2) groups. At 30 min, the LDK group showed a significantly greater mean reduction in NRS scores (3.1 ± 2.03) compared to the MOR group (1.8 ± 1.59) (p = 0.009). Similarly, at 60 min, there were significant differences in mean NRS score reductions (LDK 3.5 ± 2.17; MOR mean reduction = 2.4, ± 1.84) with a p-value of 0.04. No significant differences were observed at other time intervals. The incidence of dizziness was higher in the LDK group at 19.4% (p = 0.026).ConclusionShort infusion low-dose ketamine, as an adjunct to morphine, is effective in reducing pain during the initial 30 to 60 min and demonstrated comparability to intravenous morphine alone in reducing pain over the subsequent 60 min for acute long bone fractures. However, it was associated with a higher incidence of dizziness.Trial registrationNMRR17318438970 (2 May 2018;www.nmrr.gov.my).

Emissions and exposure to NOx, CO, CO2 and PM2.5 from a gas stove using reference and low-cost sensors

Gas stoves and cooking are significant sources of indoor pollution. Using a combination of regulatory and calibrated low-cost sensors (LCS) we measured NO, NO2, CO and CO2 emission rates (g hr−1) and emission factors (g J−1) from a natural-gas stove and oven. The emission rates for gaseous pollutants were significantly higher, by factors of 2.6–29, from the oven compared to the stove for every pollutant measured.To evaluate the indoor air concentrations, we used a calibrated low-cost sensor (TSI Inc, AirAssure) to examine indoor concentration of CO, CO2, NO2 and PM2.5 for one month in one U.S. home with a gas stove during normal activities, including cooking. Indoor concentrations of one or more pollutants exceeded the U.S. EPA's Air Quality Index (AQI) level of 100 (for CO, NO2, and PM2.5) or 2000 ppm (for CO2) for an average of 99 min per day. The AirAssure, with only the manufacturer's calibration, was an excellent indicator of times when indoor concentrations of CO, CO2, and NO2 exceeded these reference levels. Without in-situ calibration, the AirAssure underestimated in-home PM2.5 concentrations. After in-situ calibration, the AirAssure correctly identified 1-min periods when the AQI was >100 85% of the time (up from 46% of the time without calibration).

Effect of peak intensity periods on temporary fatigue and recovery kinetics in professional male football

ABSTRACT We analysed peak 1-, 2- and 5-min periods and the associated 5-min recovery period in matches from three consecutive seasons in the Danish Superliga. A semi-automatic multicamera system was used to collect high-speed running distance (≥5.5 m/s; HSRD), sprint distance (≥7.0 m/s; SpD) and distance covered during intense acceleration (≥3 m/s2; AccD). Analysis included 479 players and 6042 to 9671 match observations using rolling average. Distances covered per minute during the peak periods were significantly higher than match averages: HSRD (207–772%), SpD (447–1793%), and AccD (383–1096%). Distances covered per min were lower during 1-min recovery periods than match average for HSRD following peak 1-, 2- and 5-min period (29%, 6%, 3%, 2%, 2%; 35%, 11%, 0%, 2%, 3%; and 45%, 29%, 13%, 8%, 4%; p < 0.05, respectively), and for SpD (20%, 3%, 7%, 3% (4% higher in the 5th min); 24%, 12%, 3%, 0%, 7%; and 39%, 29%, 18%, 17%, 12%; p < 0.05, respectively). Opposite, AccD increased in the following 1-min recovery periods following peak 1-, 2- and 5-min periods (68%, 89%, 94%, 88%, 90%; 47%, 86%, 93%, 90%, 88%; 23%, 56%, 76%, 85%, 87%; p < 0.05) compared to match averages. Intensity was higher during shorter periods, whereas performance decrements were largest after longer peak periods for HSRD and SpD, whereas no decrement was observed in AccD.

Impact of Peripheral Versus Central Insulin on Cerebrovascular Compliance in Healthy Young Adults

Objective: Vascular compliance is an essential component of cerebral blood flow regulation. Prior work has shown cerebral vasodilation (elicited by hypercapnia) reduces cerebrovascular compliance (Ci); however, this work has yet to be translated to other vasoactive compounds. Insulin has important vasodilatory effects in the peripheral circulation, but less is known about the role of insulin in cerebrovascular control. Herein, we hypothesized both peripheral (intravenous) and central (intranasal) insulin administration would increase indices of cerebral blood flow and reduce Ci in healthy young adults. Methods: Twenty-five healthy young adults (8 female; 26±7 yrs, 25±3 kg/m2) were assigned to two separate protocols (NCT05244694, NCT05153395). Middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound) was measured at baseline and under two study conditions: 1) at the end of a 60 min hyperinsulinemic euglycemic infusion, and 2) 60 min following 160 IU of intranasal insulin. Indices of Ci were calculated using a modified Windkessel model applied to blood pressure (finger photoplethysmography) and corresponding MCAv waveforms collected over a 5-min period (10 waveforms) at baseline and during the aforementioned insulin conditions. Results: Blood glucose remained unchanged throughout both protocols (both p&gt;0.05). MCAv was maintained over time under both insulin conditions (protocol 1: 60±13 to 62±17 cm/s, p=0.635; protocol 2: 58±9 to 53±14 cm/s, p=0.146). In contrast, Ci decreased (0.00028±0.00010 to 0.00021±0.00007 cm/s/mmHg, p=0.010) from baseline during peripheral (intravenous) insulin administration. No change in Ci (0.00049±0.00025 to 0.00040±0.00018 cm/s/mmHg, p=0.189) were observed following intranasal insulin administration. Conclusions: Contrary to our hypothesis, there was no effect of peripheral or central insulin administration on resting MCAv in healthy young adults. However, intravenous (but not intranasal) insulin reduced Ci by approximately 25% from baseline values. These findings advance our understanding of cerebrovascular control mechanisms during insulin exposure and provide the opportunity to extend this work to diseased states characterized by insulin resistance, including diabetes. CAFNR Joy of Discovery (JKL, JP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evaluation of Thermal Support during Anesthesia Induction on Body Temperature in C57BL/6 and Nude Mice.

Heat supplementation during surgery is a common practice; however, thermal support is not commonly used during anesthesia induction. Mice lose body temperature quickly, and air movement can exacerbate this, potentially putting mice at a thermal deficit before surgery. Whether the method of warming during induction affects overall heat loss during anesthesia is unknown. We hypothesized that the method of heating would affect body temperature (Tb) during anesthesia induction, maintenance, recovery, and once placed back on the rack. Mice (C57BL/6NHsd-6M/6F [C57BL/6]; Hsd:Athymic Nude-Foxn1nu [Nude]; N = 24;12M/12F) were assigned to a treatment in a factorial design: thermal chamber (TC; ambient temperature [Ta] = 28.8°C); heating pad (HP; induction chamber placed on an electric heating pad;Ta = 28.4°C); and control (Ctrl; Ta = 21.6°C). During induction, one mouse at a time was anesthetized with isoflurane over a 3min period and then maintained under anesthesia for 10min on a hot water heating pad (33 °C). Then isoflurane was stopped and time to ambulation was recorded. Tb and activity were tracked in the home cage on the rack before and after anesthesia. During induction, Ctrl mice lost significantly more heat (-2.8 °C) than did TC (+0.2 °C) and HP mice (+0.1 °C) but TC and HP were not different. During anesthesia maintenance, Ctrl mice regained 1 °C, but their Tb was still lower than that of the treated groups. Nude mice consistently had a lower Tb than C57BL/6 mice, regardless of treatment or anesthesia phase. C57BL/6 Ctrl mice took longer to ambulate than either HP or TC mice, but the method of heating did not differentially affect Nude mice. In general, C57BL/6 as compared with Nude and females as compared with males were comparatively more active and had higher Tb during certain times of day, regardless of the heating methods. Overall, our findings support the provision of heat during anesthesia induction, regardless of method, to reduce overall Tb loss during a short anesthesia event.

Orexin 1 Receptors in The Paraventricular Nucleus of The Hypothalamus (PVN) Facilitate The Peripheral Chemoreflex

Increased sensitivity of the peripheral chemoreflex (PCR) to hypoxia is associated with cardiovascular-related diseases such as hypertension and heart failure. We previously showed that systemic blockade of both orexin 1 (Ox1R) and orexin 2 receptors reduced the PCR-mediated hypoxic ventilatory response (HVR), and that hypoxia activates PVN-projecting orexin neurons. The effect of OxR blockade on the HVR was strongest in the active phase of the circadian cycle and was associated with decreased numbers of activated neurons in the nucleus of the solitary tract (nTS) and nTS-projecting corticotropin-releasing neurons in the PVN. While the projection from the PVN to the nTS contributes to the PCR, the neuronal mechanism(s) activating this projection are unclear. We hypothesized that orexin acting at Ox1R in the PVN facilitates the PCR. To test this hypothesis, we first performed IHC to confirm the expression of Ox1R in the PVN. We then assessed the degree to which specific Ox1R blockade reduced the HVR (n=6; tested first with vehicle (100% DMSO), then Ox1R antagonist SB-334867, 1 mg/kg, i.p). To assess the contribution of PVN Ox1Rs to the PCR as well as the associated activation of neurons in the PVN and nTS, we specifically knocked down Ox1R expression in the PVN via nanoinjection of an Ox1R shRNA-GFP expressing AAV vector. Rats were exposed to graded hypoxia during the active phase, with inspired O2 taken from 21% to 11% over a ~5 min period. Rats were kept near-isocapnic by slightly increasing the inspired CO2. Subsets of rats were exposed to hypoxia to assess the effects of Ox1R on neuronal activation using c-Fos expression as a surrogate marker. Systemic Ox1R blockade significantly reduced the HVR compared to the control response (by ~30%; p=0.0027). Knockdown of Ox1R in the PVN also reduced the HVR (by ~20%; p=0.049) and reduced the number of c-Fos expressing PVN neurons in response to hypoxia (p=0.0232). More specifically, hypoxia induced c-Fos expression in fewer PVN neurons transfected with Ox1R shRNA (confirmed by GFP expression) than neurons from control rats transfected with scrambled RNA (p=0.0083). Ox1R knockdown in the PVN also significantly reduced the hypoxia-induced increase in number of c-Fos expressing tyrosine-hydroxylase (TH) nTS neurons (p=0.0303), suggesting that PVN Ox1Rs mediate hypoxia-induced activation of TH neurons in the nTS. These findings suggest that in the PVN, orexin acting at Ox1Rs mediate the facilitation of the PCR and the associated activation of the PVN and nTS neurons. Ox1R in the PVN could be a novel target to treat diseases associated with increased PCR sensitivity. Grants: 5R01HL098602 (to DK, EH and KC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lipolysis and fat oxidation decrease during postprandial lactatemia

Circulating glycerol ([glycerol]) and free fatty acid ([FFA]) concentrations decrease and lactate concentration ([lactate]) increases in response to oral glucose consumption, but the effect of increased [lactate] on the rate of lipolysis is not known. We hypothesized that whole-body lipolytic (i.e., glycerol rate of appearance, Ra) and fat oxidation (FOx) rates would decrease following oral glucose consumption and inversely correlate with an increase in [lactate] above baseline levels (i.e., lactatemia) during both enteric (0–30 min) and systemic (60–120 min) phases of the postprandial lactate shuttle (PLS). Young, healthy men and women (n=15) reported to the lab following a 12-hour overnight fast and had the forearm vein catheterized for primed continuous infusion of [1,1,2,3,3-2H]glycerol. The contralateral hand vein was warmed and catheterized for arterialized blood sampling. After a 90-min equilibration period, participants underwent a 75 g oral glucose tolerance test (OGTT). Glycerol Ra was significantly lower at 5 min (1.92 ± 0.12 μmol·kg−1·min−1) and 30–120 min during the OGTT compared to baseline (2.06 ± 0.12 μmol·kg−1·min−1). [Glycerol] was significantly lower from baseline (69.19 ± 2.50 μM) at 30 min (50.58 ± 3.01 μM) after glucose consumption, then continued to decline thereafter. Similarly, [FFA] was significantly lower from baseline (464.71 ± 27.01 μM) at 30 min (247.14 ± 32.78 μM), then continued to decline. FOx was significantly lower from baseline (0.89 ± 0.05 kcal∙min−1) at 60 min (0.58 ± 0.05 kcal∙min−1) and remained steady from then on. Concurrently, [lactate] increased from baseline (0.59 ± 0.06 mM) and was significantly higher at 5 min (0.71 ± 0.06 mM) after glucose consumption, peaked at 15 min (1.09 ± 0.01 mM), reached a nadir at 30 min, then continued to rise thereafter. There was an overall inverse correlation (r = -0.71, p = 0.07) between glycerol Ra and [lactate] during the OGTT that was also present during the enteric phase (r = -0.45, p = 0.55). Similarly, there was overall an inverse correlation between FOx and [lactate] (r = -0.57, p = 0.17), but it was not present during the enteric phase (r = 0.93, p = 0.07). However, the correlations of both glycerol Ra and FOx with [lactate] approached linearity during the systemic phase (r = 0.99, p = 0.06). The reduction in glycerol Ra at 5 min indicates a rapid decrease in the rate of lipolysis following oral glucose consumption. The correlations suggest that lactatemia may influence both glycerol Ra and FOx by exerting an inhibitory effect, particularly during the systemic phase of the PLS. However, the lag in the decrease in FOx and opposing responses of glycerol Ra and [lactate] at 5 min suggests that lactatemia may have a greater role in inhibiting whole-body lipolysis in the postprandial period. Supported by NIH grant R01 AG059715 to GAB. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Vascular responses during handgrip exercise in healthy postmenopausal females and older males

Introduction: Aerobic exercise interventions improve peripheral endothelial function in healthy older males. However, this effect is not always observed in healthy postmenopausal females and possible mechanisms underlying this sex-related difference remain unknown. Greater vascular shear stress during acute exercise is a key stimulus mediating longer-term improvements in vascular function. It remains unknown if postmenopausal females display a reduced endothelial sensitivity to exercise-induced shear stress relative to males of similar age. Objective and hypothesis: The objective of this study is to test the hypothesis that healthy postmenopausal females exhibit a lower endothelial sensitivity to exercise-induced shear stress relative to males. Methods: Fourteen healthy postmenopausal females (67 ± 8 years) not under hormone replacement therapy and 9 males of similar age (65 ± 7 years) performed handgrip exercise for 4 minutes at 20%, 40%, 60%, and 80% of their maximal voluntary contraction. Each exercise bout was separated by a 10-min recovery period. Brachial artery diameter and blood velocity were continuously measured using high-resolution ultrasound and analyzed using edge-detection software. Endothelial sensitivity to shear rate was quantified as the slope of the linear regression between brachial artery dilation (% change from baseline) and shear stress and compared between groups with an independent t-test. Workload, vascular conductance, diameter dilation, and shear stress were analyzed with mixed-effects models. Results: Males exercised at greater workloads relative to females across all exercise bouts (M: 17 ± 11 vs. F: 9 ± 5 kg, p&lt;0.01). Forearm vascular conductance was greater in males throughout each exercise intensity (M: 2.23 ± 1.70 vs. F: 1.03 ± 0.51 ml/min/mmHg, p=0.02). Despite these differences, arterial dilation (M: 5.32 ± 5.55 vs. F: 5.20 ± 4.80%, p=0.96) and shear stress (M: 142 ± 80 vs. F: 171 ± 86 s−1, p=0.27) did not differ between groups across exercise intensities. Endothelial sensitivity to exercise-induced shear stress did not differ between males (0.02 ± 0.05%/s−1) and females (0.03 ± 0.01%/s−1, p=0.67). Conclusion: These data suggest that a reduced endothelial sensitivity to exercise-induced shear stress may not explain why aerobic exercise interventions do not consistently improve peripheral endothelial function in healthy postmenopausal females. Montreal Heart Institute Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.