Control Of Mean Arterial Pressure Research Articles

Adaptive Drug Delivery to Control Mean Arterial Blood Pressure by Reinforcement Fuzzy Q-Learning

Adaptive Drug Delivery to Control Mean Arterial Blood Pressure by Reinforcement Fuzzy Q-Learning

Coronary and Systemic Vasodilator Responsiveness of Patients Receiving Conventional Intermittent or Nocturnal Hemodialysis.

Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown. We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin. Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P<0.03) but attenuated, relative to controls (4.80±0.63; P=0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort (P<0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P<0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P<0.05, all comparisons). Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis.

Computer-controlled closed-loop norepinephrine infusion system for automated control of mean arterial pressure in dogs under isoflurane-induced hypotension: a feasibility study.

Intra-operative hypotension is a common complication of surgery under general anesthesia in dogs and humans. Computer-controlled closed-loop infusion systems of norepinephrine (NE) have been developed and clinically applied for automated optimization of arterial pressure (AP) and prevention of intra-operative hypotension in humans. This study aimed to develop a simple computer-controlled closed-loop infusion system of NE for the automated control of the mean arterial pressure (MAP) in dogs with isoflurane-induced hypotension and to validate the control of MAP by the developed system. NE was administered via the cephalic vein, whereas MAP was measured invasively by placing a catheter in the dorsal pedal artery. The proportional-integral-derivative (PID) controller in the negative feedback loop of the developed system titrated the infusion rate of NE to maintain the MAP at the target value of 60 mmHg. The titration was updated every 2 s. The performance of the developed system was evaluated in six laboratory Beagle dogs under general anesthesia with isoflurane. In the six dogs, when the concentration [median (interquartile range)] of inhaled isoflurane was increased from 1.5 (1.5-1.5)% to 4 (4-4)% without activating the system, the MAP was lowered from 95 (91-99) to 41 (37-42) mmHg. In contrast, when the concentration was increased from 1.5 (1.0-1.5)% to 4 (4-4.8)% for a 30-min period and the system was simultaneously activated, the MAP was temporarily lowered from 92 (89-95) to 47 (43-49) mmHg but recovered to 58 (57-58) mmHg owing to the system-controlled infusion of NE. If the acceptable target range for MAP was defined as target MAP ±5 mmHg (55 ≤ MAP ≤65 mmHg), the percentage of time wherein the MAP was maintained within the acceptable range was 96 (89-100)% in the six dogs during the second half of the 30-min period (from 15 to 30 min after system activation). The median performance error, median absolute performance error, wobble, and divergence were - 2.9 (-4.7 to 1.9)%, 2.9 (2.0-4.7)%, 1.3 (0.8-1.8)%, and - 0.24 (-0.34 to -0.11)%·min-1, respectively. No adverse events were observed during the study period, and all dogs were extubated uneventfully. This system was able to titrate the NE infusion rates in an accurate and stable manner to maintain the MAP within the predetermined target range in dogs with isoflurane-induced hypotension. This system can be a potential tool in daily clinical practice for the care of companion dogs.

Spiritual Meaning Impacts Psychological Distress and Control of Mean Arterial Pressure in Hypertension Patients

Hypertension is a disease that can cause various complications and is made worse by psychological distress, where cases are increasing at the Bangkalan Community Health Center. This research aims to analyze the correlation between spiritual meaning in regulating psychological distress and mean arterial pressure (MAP) in hypertension patients. This research method is correlation analytic with a cross-sectional approach with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. population of 76 patients and a sample of 62 taken using simple random sampling. The independent variable is spiritual meaning, measured using the Daily Spiritual Experience Scale (DSES). Meanwhile, the dependent variable is distress, measured by the Kessler Psychological Distress Scale and the mean arterial pressure (MAP) value. The collected data was then subjected to statistical tests using Spearman ranks with an alpha value of 0.05. The research results show a relationship between spiritual meaning and psychological distress with a p-value of 0.016 &lt; 0.05 and a correlation coefficient of -0.305. Spirituality is also significantly related to the mean arterial pressure (MAP) value with p value 0.005 &lt; 0.05, and the correlation coefficient is -0.351. Spirituality has an impact on reducing psychological distress, affecting the function of the Hypothalamus Pituitary Adrenal (HPA) Axis and Sympathetic Adrenal Medullary (SAM) Axis. The SAM Axis will balance the secretion of norepinephrine (NE) and epinephrine (E), which affects the balance of contraction of smooth cardiac muscle cells, vasoconstriction and vasodilation, heart rate, and normalizes sodium levels so that it can control blood pressure in hypertensive patients.

Muscle metaboreflex stimulates the cardiac sympathetic afferent reflex causing positive feedback amplification of sympathetic activity: effect of heart failure.

Exercise intolerance is a hallmark symptom of heart failure and to a large extent stems from reductions in cardiac output that occur due to the inherent ventricular dysfunction coupled with enhanced muscle metaboreflex-induced functional coronary vasoconstriction, which limits increases in coronary blood flow. This creates a further mismatch between O2 delivery and O2 demand, which may activate the cardiac sympathetic afferent reflex (CSAR), causing amplification of the already increased sympathetic activity in a positive-feedback fashion. We used our chronically instrumented conscious canine model to evaluate if chronic ablation of afferents responsible for the CSAR would attenuate the gain of muscle metaboreflex before and after induction of heart failure. After afferent ablation, the gain of the muscle metaboreflex control of mean arterial pressure was significantly reduced before (-239.5 ± 16 to -95.2 ± 8 mmHg/L/min) and after the induction of heart failure (-185.6 ± 14 to -95.7 ± 12 mmHg/L/min). Similar results were observed for the strength (gain) of muscle metaboreflex control of heart rate, cardiac output, and ventricular contractility. Thus, we conclude that the CSAR contributes significantly to the strength of the muscle metaboreflex in normal animals with heart failure serving as an effective positive-feedback amplifier thereby further increasing sympathetic activity.NEW & NOTEWORTHY The powerful pressor responses from the CSAR arise via O2 delivery versus O2 demand imbalance. Muscle metaboreflex activation (MMA) simultaneously elicits coronary vasoconstriction (which is augmented in heart failure) and profound increases in cardiac work thereby upsetting oxygen balance. Whether MMA activates the CSAR thereby amplifying MMA responses is unknown. We observed that removal of the CSAR afferents attenuated the strength of the muscle metaboreflex in normal and subjects with heart failure.

Cardiovascular evaluation and endothelial dysfunction in Cushing syndrome following remission: a prospective study.

Cushing syndrome (CS) is a well-known risk factor for cardiovascular morbidities. We aimed to evaluate endothelial and cardiovascular functions, endothelial mediators and pro-inflammatory cytokines in patients with CS before and after remission. Adult patients with newly diagnosed endogenous CS were included. Metabolic [body mass index (BMI), glucose, and lipid values] and cardiovascular evaluation studies [24-h ambulatory blood pressure monitoring, carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and echocardiography] were performed, and endothelial mediators [asymmetric dimethyl arginine (ADMA) and endothelin-1 (ET-1)] and pro-inflammatory cytokines [interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α)] were measured. Control group was matched in terms of age, gender, and BMIs. Twenty-five patients, mean age 40.60 ± 14.04years, completed the study. Compared to controls (n = 20) mean arterial pressure (MAP) and CIMT were higher (p < 0.005 and p = 0.012, respectively), and FMD (p < 0.001) and mitral E/A ratio (p = 0.007) lower in the patients during active disease. Baseline serum ADMA, ET-1, and IL-1β were similar between the groups, while TNF-α was lower in the patients (p = 0.030). All patients were in complete remission 1 year following surgery. BMI, LDL cholesterol, serum total cholesterol, fasting plasma glucose, MAPs, and CIMT significantly decreased (p < 0.005), while there was no improvement in FMD (p = 0.11) following remission. There was no significant change in ADMA, IL-1β, and TNF-α levels, but ET-1 increased (p = 0.011). Remission in CS improves some cardiovascular parameters. ADMA and ET-1 are not reliable markers for endothelial dysfunction in CS. Metabolic improvements may not directly reflect on serum concentrations of TNF-α and IL-1β following remission of CS.

PS-B05-7: HYPERTENSION IN A MODEL OF PKD IS NOT DEPENDENT ON THE SHORT-TERM ACTIONS OF TUMOUR NECROSIS FACTOR-A IN THE SFO

Objective: The development of hypertension in the Lewis polycystic kidney (LPK) disease model of kidney disease is caused, in part, by neuronal overactivity in the subfornical organ (SFO). Circulating proinflammatory cytokines, namely TNFα, are suggested to act in the central nervous system to produce an increase in neuronal excitability. As circulating cytokines are increased in kidney disease, we hypothesised that TNFα acts on the SFO to increase neuronal activity, therefore contributing to the development of hypertension in this animal model. Design and Methods: Urethane anaesthetised Lewis control (n = 23 total) and LPK (n = 18 total) animals were instrumented to record blood pressure and perform microinjections of TNFα (1–300pg/50nl), TNFα receptor 1 (TNFRI) neutralising antibody (1ng/50nl) or minocycline (0.5 μg/50nl), an inhibitor of microglial activation. Results: Exogenous TNFα microinjected into the SFO elicited a significant pressor response in the Lewis control but not the LPK animals (9 ± 2 mmHg vs -1 ± 3 mmHg, Lewis vs LPK peak change from baseline, P = 0.04). Acute inhibition of actions of local TNFα via administration of TNFRI neutralising antibody in the SFO did not reduce mean arterial blood pressure in Lewis control or LPK animals (1 ± 1mmHg vs -1 ± 1mmHg, Lewis vs LPK change from baseline, P = 0.59). Acute blockade of the actions of all proinflammatory cytokines on microglia via microinjection of minocycline in the SFO did not reduce blood pressure in Lewis control or LPK animals (-1 ± 1mmHg vs -1 ± 1mmHg, Lewis vs LPK change from baseline, P = 0.11). Prior microinjection of TNFRI neutralising antibody into the SFO abolished the pressor response observed upon microinjection of TNFα in Lewis rats (9 ± 2 mmHg vs 1 ± 1 mmHg, TNFα vs TNFα after TNFRI Ab peak change from baseline, P = 0.01), whereas prior microinjection of minocycline into the SFO only attenuated the pressor response observed upon TNFα microinjection in Lewis rats (9 ± 2 mmHg vs 3 ± 1 mmHg, TNFα vs TNFα after Minocycline peak change from baseline, P = 0.04) Conclusions: Overall, these findings demonstrate that although hypertension observed in the LPK is sustained by an increase in SFO activity, the short-term control of mean arterial blood pressure activity is not dependent on the actions of endogenous TNFα or generalised microglial activation by proinflammatory cytokines in the SFO.

Differential effects of estrogen receptors in the rostral ventrolateral medulla in Goldblatt hypertension

Previous studies have shown that 17β-estradiol plays a cardioprotective role in the central nervous system (CNS) of male rats. The aim of the present study was to determine the influence of 17β-estradiol on sympathetic vasomotor activity and blood pressure in a renovascular hypertensive Goldblatt two-kidney one-clip (2K-1C) male rat model. We also determined the influence of angiotensin II AT1 receptor on the expression of estrogen receptors (ERα, ERβ, and G protein-coupled ER (GPER)) in the rostral ventrolateral medulla (RVLM) of Goldblatt rats. Experiments were performed in Goldblatt and age-matched control rats six weeks after clipping of renal artery to induce hypertension. Microinjection of 17β-estradiol into the RVLM led to a greater reduction in mean arterial pressure and renal sympathetic nerve activity in controls than in 2K-1C rats. Microinjection of the GPER agonist G-1 into the RVLM led to a significantly greater increase in mean arterial pressure and renal sympathetic nerve activity in 2K-1C rats. Expression levels of estrogen receptors GPER and ERα, but not ERβ, were significantly higher in the RVLM of 2K-1C rats than in that of the control rats. Chronic treatment with losartan significantly reduced the expression levels of estrogen receptors in the RVLM of 2K-1C rats. Taken altogether, the data suggest that the imbalance of actions between ERα and GPER, particularly with the predominance of GPER in the RVLM, contributes to sympathetic overactivation in male rats with Goldblatt hypertension. AT1-Angiotensin II receptor in the RVLM upregulated estrogen receptor expression in male Goldblatt rats.

The drug titration paradox: more drug does not correlate with more effect in individual clinical data

BackgroundA fundamental concept in pharmacology is that increasing dose increases drug effect. This is the basis of anaesthetic titration: the dose is increased when increased drug effect is desired and decreased when reduced drug effect is desired. In the setting of titration, the correlation of doses and observed drug effects can be negative, for example increasing dose reduces drug effect. We have termed this the drug titration paradox. We hypothesised that this could be explained, at least in part, by intrasubject variability. If the drug titration paradox is simply an artifact of pooling population data, then a mixed-effects analysis that accounts for interindividual variability in drug sensitivity should ‘flip’ the observed correlation, such that increasing dose increases drug effect. MethodsWe tested whether a mixed-effects analysis could correctly reveal the underlying pharmacology using previously published data obtained during automatic feedback control of mean arterial pressure (MAP) with alfentanil (effect site concentration, CeAlf) during surgery. The relationship between MAP and CeAlf was explored with linear regression and a linear mixed-effects model. ResultsA linear mixed-effects model did not identify the correct underlying pharmacology because of the presence of the titration paradox in the individual data. ConclusionsThe relationship between drug dose and drug effect must be determined under carefully controlled experimental conditions. In routine care, where the effect is profoundly influenced by varying clinical conditions and drugs are titrated to achieve the desired effect, it is nearly impossible to draw meaningful conclusions about the relationship between dose and effect.

A Computational Hemodynamics Approach to Left Ventricular Assist Device (LVAD) Optimization Validated in a Large Patient Cohort.

With increasing use of left ventricular assist devices (LVAD) it is critical to devise strategies to optimize LVAD speed while controlling mean arterial pressure (MAP) and flow according to patient physiology. The complex interdependency between LVAD speed, MAP, and flow frequently makes optimization difficult under clinical conditions. We propose a method to guide this procedure in silico, narrowing the conditions to test clinically. A computational model of the circulatory network that simulates HF and LVAD support, incorporating LVAD pressure-flow curves was applied retrospectively to anonymized patient hemodynamics data from the University of Washington Medical Center. MAP management on 61 patient-specific computational models with a target of 70 mm Hg, resulting flow for a given LVAD speed was analyzed, and compared to a target output of 5 L/min. Before performing virtual MAP management, 51% had a MAP>70 mm Hg and CO>5 L/min, and 33% had a MAP>70 mm Hg and CO<5 L/min. After changing systemic resistance to meet the MAP target (without adjusting LVAD speed), 84% of cases resulted in CO higher than 5 L/min, with a median CO of 6.79 L/min, using the computational predictive model. Blood pressure management alone is insufficient in meeting both MAP and CO targets, due to the risk of hypervolemia, and requires appropriate LVAD speed optimization to achieve both targets, while preserving right heart health. Such computational tools can narrow down conditions to be tested for each patient, providing significant insight into the pump-patient interplay. LVAD hemodynamic optimization has the potential to reduce complications and improve outcomes.

Hypertension in an Animal Model of Kidney Disease is not Dependent on the Short‐Term Actions of Endogenous Tumour Necrosis Factor‐α in the SFO

Introduction The development of hypertension in the Lewis polycystic kidney (LPK) disease model of kidney disease is caused, in part, by the overactivation of the subfornical organ (SFO). Circulating proinflammatory cytokines, namely tumour necrosis factor-α (TNFα), are suggested to act in the central nervous system to produce an increase in neuronal excitability. As circulating cytokines are increased in kidney disease, we hypothesised that TNFα acts on the SFO to increase neuronal activity, therefore contributing to the development of hypertension. Methods Urethane anaesthetised Lewis control (n=18 total) and LPK (n=18 total) rats were instrumented to record blood pressure and perform microinjections of TNFRI neutralising antibody (1ng/50nl) or minocycline (0.5µg/50nl), an inhibitor of microglial activation, followed by a GABAa agonist (10mM isoguvacine) into the SFO. Results Exogenous TNFα microinjected into the SFO elicited a significant pressor response in the Lewis control but not the LPK rats (9±2mmHg vs 3±4mmHg peak change from baseline, P=0.0004). Acute inhibition of local TNFα by microinjection of a TNFRI neutralising antibody into the SFO did not reduce mean arterial blood pressure in Lewis control or LPK rats (1±1mmHg vs -1±1mmHg change from baseline, P=0.78). Similarly, acute non-specific blockade of proinflammatory cytokines by microinjection of minocycline in the SFO did not reduce blood pressure in Lewis control or LPK rats (-1±1mmHg vs -1±1mmHg change from baseline, P=0.98). Microinjection of a GABAa agonist into the SFO caused a significant depressor response that was not altered by the pre-treatment with a microinjection of TNFRI neutralising antibody in either strain (P>0.05), demonstrating that pre-treatment did alter the tonic activation of neurons within the SFO. Interestingly, pre-treatment with a microinjection of minocycline increased the tonic activation in the LPK (P=0.04), but not Lewis (P=0.15), as indicated by the increased depressor response to GABAa agonist microinjection. Conclusions Overall, these findings demonstrate that although the hypertension observed in the LPK is sustained by an increase in SFO activity, the short-term control of blood pressure is not dependent on the actions of endogenous TNFα or generalised microglial and neuronal activation by proinflammatory cytokines in the SFO.

Cardiorespiratory responses to high-intensity skeletal muscle metaboreflex activation in chronic obstructive pulmonary disease.

Augmented skeletal muscle metaboreflex activation may accompany chronic obstructive pulmonary disease (COPD). The maintained metaboreflex control of mean arterial pressure (MAP) that has been reported may reflect limited evaluation using only one moderate bout of static handgrip (HG) and following postexercise ischaemia (PEI). We tested the hypothesis that cardiovascular and respiratory responses to high-intensity static HG and isolated metaboreflex activation during PEI are augmented in COPD patients. Ten patients with moderate to severe COPD and eight healthy age- and BMI-matched controls performed two-minute static HG at moderate (30% maximal voluntary contraction; MVC) and high (40% MVC) intensity followed by PEI. Despite similar ratings of perceived exertion, arm muscle mass and strength, COPD patients demonstrated lower MAP responses during both HG intensities compared with controls (time×group interaction, p<.05). Indeed, during high-intensity HG at 40% MVC, peak MAP responses were significantly lower in COPD patients (ΔMAP: COPD 41±9mmHg vs. controls 56±14mmHg, p<.05). Notably, no group differences in MAP were observed during PEI (e.g. 40% MVC PEI: ΔMAP COPD 33±9mmHg vs. controls 33±6mmHg, p>.05). We found no between-group differences in heart rate, respiratory rate, or estimated minute ventilation during HG or PEI. These results suggest that the pressor response to high-intensity HG is blunted in COPD patients. Moreover, despite inducing a strong cardiovascular and respiratory stimulus, skeletal muscle metaboreflex activation evoked similar responses in COPD patients and controls.

Adaptive optimal target controlled infusion algorithm to prevent hypotension associated with labor epidural: An adaptive dynamic programming approach

Patients receiving labor epidurals commonly experience arterial hypotension as a complication of neuraxial block. The purpose of this study was to design an adaptive optimal controller for an infusion system to regulate mean arterial pressure. A state–space model relating mean arterial pressure to Norepinephrine (NE) infusion rate was derived for controller design. A data-driven adaptive optimal control algorithm was developed based on adaptive dynamic programming (ADP). The stability and disturbance rejection ability of the closed-loop system were tested via a simulation model calibrated using available clinical data. Simulation results indicated that the settling time was six minutes and the system showed effective disturbance rejection. The results also demonstrate that the adaptive optimal control algorithm would achieve individualized control of mean arterial pressure in pregnant patients with no prior knowledge of patient parameters.

Leptin-Mediated Sympathoexcitation in Obese Rats: Role for Neuron-Astrocyte Crosstalk in the Arcuate Nucleus.

IntroductionAccumulated evidence indicates that obesity is associated with enhanced sympathetic activation. Hypothalamic leptin-mediated signaling may contribute to the exaggerated sympathoexcitation of obesity. The goal of this study was to investigate the “neuron–astrocyte” interaction affecting leptin-mediated sympathoexcitation within the arcuate nucleus (ARCN) of the hypothalamus in obese rats.Methods and ResultsObesity was induced by high-fat diet (HFD, 42% of calories from fat) in Sprague Dawley rats. Twelve weeks of HFD produced hyperleptinemia, hyperlipidemia, and insulin resistance. In anesthetized rats, microinjections of leptin into the ARCN induced increases in heart rate (HR), renal sympathetic nerve activity (RSNA), and mean arterial pressure (MAP) in both control and HFD rats. However, microinjections of leptin in HFD rats elicited higher responses of RSNA and arterial pressure than control-fed rats. It also caused the inhibition of astrocytes within the ARCN using an astrocytic metabolic inhibitor, fluorocitrate, and reduced leptin-induced sympathetic activity and blood pressure responses. Moreover, the expression of the leptin receptor in the ARCN of HFD-fed rats was significantly increased compared to rats fed a control diet. Immunohistochemistry analysis revealed leptin receptor localization from both neurons and astrocytes of the ARCN. HFD rats exhibited increased protein expression of glial fibrillary acidic protein (GFAP) in the ARCN. We also found that the expression of astrocyte-specific glutamate transporters and excitatory amino acid transporter 1 (EAAT1) and 2 (EAAT2) were decreased within the ARCN of the HFD rats. In cultured astrocytic C6 cells, 24 h of leptin treatment increased the protein expression of GFAP and reduced the expression of EAAT1 and EAAT2.ConclusionThe results suggest that central leptin signaling occurs via neuron-astrocyte interactions in the ARCN and contributing to the exaggerated sympathoexcitation observed in obese rats. The effects may be mediated by the action of leptin on regulating astrocytic glutamate transporters within the ARCN of the hypothalamus.

Manual vs Closed-loop Control of Mean Arterial Pressure

Manual vs Closed-loop Control of Mean Arterial Pressure

Simple adaptive PI controller development and evaluation for mean arterial pressure regulation

The automatic control of mean arterial pressure (MAP) in post-cardiac surgery has many advantages for patients and medical staff. However, it is a challenging problem for the control engineering and biomedical engineering community. Successfully developed controllers in the research environment have not been successful in the market because of their complex implementation, complicated operation, and inadequate capabilities performance across the range of patient variabilities. This paper describes the development and testing of a simple embedded adaptive PI controller for automatic MAP regulation of a known range of patients. The developed controller is a synergistic combination of simple and proved schemes that have complementary characteristics; it is a parameter estimator for identification of patient MAP parameters, calculation of patient sensitivity, and adjustment of gains of a specific proportional-integral controller for the identified patient. The controller was implemented in Matlab/Simulink for desktop simulation along with a MAP model that allows the variation of the type of patient tested. In addition to the desktop simulation, an embedded version of the controller implemented in ARM Cortex M3 low-cost microcontroller was tested on a hardware-in-the-loop (Hil) simulation along with a real-time MAP model embedded in ARM Cortex A7 single board computer. Both simulations (desktop and hardware-in-the-loop) presented similar results, meeting the established MAP regulation performance criteria: settling time less than 600 s, overshoot less than 10 mmHg, and steady-state error about setpoint less than 5 mmHg. The results achieved are as follows: settling time between 170 and 330 s, overshoot between 1 and 4 mmHg, and steady-state errors about setpoint less than 3 mmHg, across the range of MAP patients considered. The controller developed in this work is a viable alternative to the complicated identification and control techniques normally employed for automatic MAP regulation. An adaptive, simple PI controller for adjusting the MAP and having low computational cost was developed and embedded in a low-cost microcontroller. The controller was evaluated via desktop and Hil simulation across the known range of MAP parameters of patients, with successful regulation of MAP in all cases considered.

Cerebral Blood Flow Ultrasonography as a Diagnostic Tool for Monitoring Recovery from Concussion in Children and Adolescents

Approximately 70% of concussions are sports‐related, accounting for up to 1.9 million children and adolescents in the USA every year. Despite the high rates of injury, there are currently no consistent agreements regarding objective measures of diagnosis or severity of injury. Our pilot study determined whether cerebral blood flow (CBF) in the internal carotid artery can be utilized as an objective marker of concussion and recovery trajectory in concussed children and adolescents. We recruited individuals being seen at a concussion clinic with post concussive symptoms (mean= 40 ± 31 days post injury; range= 8–101 days) vs a group of controls who were being seen at the clinic for musculoskeletal injury. Concussed (n=10, 7 male; 12 ± 3 years) and healthy controls (n=8, 5 male; 13 ± 2 years) underwent ultrasound assessments of internal carotid artery blood flow during resting conditions when seated and supine. Continuous blood pressure, ECG, and end‐tidal CO2 were also obtained in participants. Preliminary results showed a trend for an increase in CBF in concussed children when seated (concussed= 644 ± 167 ml/min vs control= 535 ± 118 ml/min; p=0.122) but not when supine (concussed= 628 ± 142 ml/min vs control= 602 ± 140 ml/min; p=696). When comparing the percent of supine CBF when seated, concussed children showed a trend for greater CBF (concussed= 104 ± 19% vs control= 90 ± 11% p=0.101). Interestingly, in our 10 concussed participants, the ratio of seated to supine CBF negatively correlated with the number of days since injury (r= −0.738; p=0.015), suggesting elevated seated CBF may be returning towards normal values. There were no differences in end‐tidal CO2 between concussed and controls when seated (concussed= 40.4 ± 3.0 mmHg vs control= 40.8 ± 3.3 mmHg) or supine (concussed= 40.4 ± 3.8 mmHg vs control= 41.1 ± 3.8 mmHg). However there was significantly increased mean arterial pressure in controls when supine (concussed= 83.4 ± 4.8 mmHg vs control= 92.4 ± 11.9 mmHg; p=0.036) and a trend when seated (concussed= 86.2 ± 5.2 mmHg vs control= 96.0 ± 12.2 mmHg; p=0.074). If additional subjects follow the same pattern, our preliminary data would suggest that concussed children appear to be hyperperfused when seated. While it is unclear why CBF may be elevated when seated, one possibility is that flow is matching the increased metabolic demand associated with neural remodeling after injury. Our preliminary data supports that ultrasonography may be a useful diagnostic tool to monitor recovery from concussion in children and adolescents when taking into account body posture.Support or Funding InformationThe study was supported by the MARCS Institute for Brain, Behaviour and Development, Western Sydney University, Sydney, AUS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A11105 Effect of Posterior Circulation Revascularization on Blood Pressure in Hypertensive Patients

Objectives: To evaluate the effect of posterior circulation revascularization on blood pressure in hypertensive patients with symptomatic proximal subclavian or vertebral artery stenosis. Methods: A total of 48 patients with essential hypertension (33 males; mean age 63.0 ± 8.7 years) with symptomatic proximal subclavian or vertebral artery stenosis underwent stenting successfully at the Fuwai Hospital were prospectively enrolled in the study between January 2014 and June 2016. All 48 patients were followed up at 1, 3 and 6 months after the procedure. Blood pressure, use of antihypertensive agents, and complications were investigated. Results: Baseline values included mean office blood pressure of 132/77 ± 10/8 mm Hg, 24-hour mean blood pressure of 127/75 ± 12/9 mm Hg, and mean 1.6 ± 0.8 antihypertensive agents. The mean stenosis of subclavian and vertebral artery decreased from 88.9 ± 9.5% and 85.8 ± 7.4% to 5.5 ± 3.5% and 4.6 ± 3.7% immediately after the procedure, respectively. Mean reductions in office blood pressure were −7/−3 (95% CI 3/2), −9/−4 (5/3), and −10/−5 mm Hg (7/5) at 1, 3, and 6 months, respectively. 24-hour mean blood pressures after procedure were reduced by −5/−3 mm Hg at 6 months, and the total number of antihypertensive agents at the above corresponding time points essentially unchanged. Conclusion: This first prospective cohort study in human showed posterior circulation revascularization seems to be effective in reducing blood pressure in hypertensive patients. Our research outcome validates the results of previous animal experiments, suggesting the Cushing's mechanism play an important role in the long-term control of mean arterial pressure of human.

Leptin‐mediated Sympatho‐excitation in Obese Rats: Role for Astrocyte‐Neuron Crosstalk in the Arcuate Nucleus

Accumulated evidence indicates that enhanced sympathetic activation is associated with obesity. Hypothalamic leptin‐mediated signaling may contribute to the exaggerated sympatho‐excitation in obesity. The present study was conducted to investigate “neuron‐astrocyte” interactions regulating leptin signaling within the arcuate nucleus (ARCN) of hypothalamus in obese rats. High‐fat diet (42% fat for 12 weeks) induced hyperlipidemia and hyperleptinemia in Sprague Dawley rats. In anaesthetized condition, microinjections of leptin (5ng~100ng) and N‐methyl‐D‐aspartate (NMDA 50–200pmol) into the ARCN induced increases in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in both control and obese rats. Pre‐inhibition of astrocytes with astrocytic metabolic inhibitor fluorocitrate reduced leptin‐induced, but not NMDA‐induced RSNA and MAP within the ARCN. In the ARCN, leptin/leptin receptor is localized in both neurons and astrocytes. In obese rats, leptin and leptin receptor were increased in the ARCN, particularly increased more in the astrocytes than in the neurons. Furthermore, we found that the expressions of glutamate transporter GLT1 and excitatory amino acid transporter‐2 (EAAT‐2) which are major glutamate transporters expressed predominantly in astrocytes were decreased within the ARCN in obese rats. Consistent with these in‐vivo observations, in cultured astrocytic C6 cells, GLT1 and EAAT‐2 levels decreased with leptin (100 ng/ml) treatment for 24 hours. Taken together, these results suggest leptin signaling via neuron‐astrocytes interactions in the ARCN may contribute to the exaggerated sympatho‐excitation observed in obese rats. This effect maybe mediated by the action of leptin regulating glutamate transporters in the astrocytes within the ARCN of the hypothalamus.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Identifying the role of group III/IV muscle afferents in the carotid baroreflex control of mean arterial pressure and heart rate during exercise.

We investigated the contribution of group III/IV muscle afferents to carotid baroreflex resetting during electrically evoked (no central command) and voluntary (requiring central command) isometric knee extension exercise. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ-opioid receptor-sensitive group III/IV leg muscle afferent feedback. Spontaneous carotid baroreflex control was assessed by loading and unloading the carotid baroreceptors with a variable pressure neck chamber. Group III/IV muscle afferents did not influence spontaneous carotid baroreflex responsiveness at rest or during exercise. Afferent feedback accounted for at least 50% of the exercise-induced increase in the carotid baroreflex blood pressure and heart rate operating points, adjustments that are critical for an appropriate cardiovascular response to exercise. These findings suggest that group III/IV muscle afferent feedback is, independent of central command, critical for the resetting of the carotid baroreflex blood pressure and heart rate operating points, but not for spontaneous baroreflex responsiveness. This study sought to comprehensively investigate the role of metabolically and mechanically sensitive group III/IV muscle afferents in carotid baroreflex responsiveness and resetting during both electrically evoked (EVO, no central command) and voluntary (VOL, requiring central command) isometric single-leg knee-extension (15% of maximal voluntary contraction; MVC) exercise. Participants (n=8) were studied under control conditions (CTRL) and following lumbar intrathecal fentanyl injection (FENT) to inhibit μ-opioid receptor-sensitive lower limb muscle afferents. Spontaneous carotid baroreflex control of mean arterial pressure (MAP) and heart rate (HR) were assessed following rapid 5s pulses of neck pressure (NP, +40mmHg) or suction (NS, -60mmHg). Resting MAP (87±10mmHg) and HR (70±8bpm) were similar between CTRL and FENT conditions (P>0.4). In terms of spontaneous carotid baroreflex responsiveness, FENT did not alter the change in MAP or HR responses to NP (+13±5mmHg, P=0.85; +9±3bpm; P=0.99) or NS (-13±5mmHg, P=0.99; -24±11bpm; P=0.49) at rest or during either exercise protocol, which were of a remarkably similar magnitude to rest. In contrast, FENT administrationreduced the exercise-induced resetting of the operating point for MAP and HR during both EVO (116±10mmHg to 100±15mmHg and 93±14bpm to 82±10bpm) and VOL (107±13mmHg to 100±17mmHg and 89±10bpm to 72±10bpm) exercise bouts. Together, these findings document that group III/IV muscle afferent feedback is critical for the resetting of the carotid baroreflex MAP and HR operating points, independent of exercise-induced changes in central command, but not for spontaneous carotid baroreflex responsiveness.