Induced Blood Pressure Changes Research Articles

Immune Metabolic Reprogramming by Excess Dietary Salt in Salt Sensitive Hypertension via CXCL8

Salt sensitivity of blood pressure (SSBP) is when blood pressure changes parallel to salt loading/ depletion and is an independent risk factor for cardiovascular disease. Despite its importance, there is no feasible diagnosis, which limits investigational studies to identify therapeutic targets. We have found that immune cells mediate SSBP via Epithelial Sodium Channel (ENaC). CXCL8/(IL-8), a known chemoattractant plays a well-known role in glycolysis. We hypothesize that CXCL8 mediates immune metabolic reprogramming of immune cells to glycolysis via ENaC. To test this hypothesis, we performed bulk and single cell RNA sequencing in human monocytes from individuals from a modified Weinberger inpatient salt loading/ depletion protocol. The participants were instructed to refrain from taking their blood pressure medication for 2 weeks prior to the salt loading/depletion protocol. Blood and urine samples were collected, as well as ambulatory blood pressure recording. We found that changes in immune cell activation via isolevuglandin (IsoLG) protein-adducts mirror changes in salt balance and blood pressure in salt sensitive but not salt resistant individuals. We confirmed that these in vivo changes can be recapitulated in vitro. In addition, we found that salt-loading both in vivo and in vitro increases antigen presenting cell production of IL-8, which was reversed after salt depletion in salt sensitive, but not salt resistant people. ENaC inhibition by amiloride prevented the high salt-induced production of IL-8. Moreover, high salt induced blood pressure changes of expression of CXCL8 (p = 0.01553, r = 0.8067) were significant along with varying expression of glycolytic genes, including hexokinase 1(HK1)(p = 0.04190, r = -0.7249), phosphofructokinase (PFKP)(p = 0.05932, r = 0.6879) and galactose mutarotase (GALM) (p = 0.04176, r = 0.5138). Seahorse analysis revealed increased extracellular acidification rate (ECAR) in high salt conditioned monocytes, which was associated with mitochondrial dysfunction. Our results suggest that high salt intake reprograms antigen presenting cell metabolism to glycolysis via IL-8 signaling. Furthermore, targeting IL-8 and mitochondrial switching to glycolysis may not only provide novel therapeutic approaches, but also important biomarkers for diagnosis of salt sensitivity of blood pressure. 1R03HL155041-01 (Kirabo, PI), 1R01HL144941-01A1 (Kirabo, PI), 5R01HL147818-22 (Kleyman & Kirabo), 1R01HL157584-01 (Shibao, Kirabo — MPI), R01DK135764 (Kon, Shelton, Kirabo — MPI), R21TW012635 (Kirabo, Masenga — MPI), Meharry Medical College: School of Graduate Studies T32AI007281, T32GM14492, andT32HL00773. 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.

24-HOUR AMBULATORY BLOOD PRESSURE MEASUREMENT USING A PULSE ARRIVAL TIME BASED BLOOD PRESSURE MODEL BY A PROTOTYPE WEARABLE SENSOR

Objective: Methods to enable cuffless blood pressure (BP) have gained widespread interest. If proven to be comparable to standard cuff measurements and more accepted by patients, these methods can improve hypertension care. We investigated accuracy and patient acceptability of a pulse arrival time (PAT) based model using a prototype cuffless device on the chest compared to standard 24-hour ambulatory blood pressure monitoring (24hABPM). Design and method: PAT was calculated using the electrocardiogram (ECG) and photoplethysmography (PPG) sensors incorporated in the chest belt. The model to predict BP from PAT was developed from a general population cohort during isometric exercise induced BP changes. Ninety-four normotensive and hypertensive adults underwent simultaneous 24hABPM with the prototype chest belt sensor and a validated cuff-based oscillometric device on the non-dominant arm. PAT-based BP predictions were compared to reference BPs using 2-minute time windows corresponding to reference measurements. Statistical analyses were performed using Stata® v. 17.0 (Statacorp., Texas, USA) with continuous data presented as means (SD) and compared using paired t-test. Correlation analysis and agreement were evaluated by Bland-Altman plots. Results: Mean age (SD) was 48.1 (14.3) years and 48 % had a prior hypertension diagnosis. Comparisons between reference and PAT-based mean 24-hour, daytime and nighttime BP showed that the PAT-based model generally overestimated BP (Table). The largest difference was seen during nighttime; the mean difference (SD) was 19.6 (22.2) mmHg and 17.0 (12.2) mmHg for systolic BP (SBP) and diastolic BP (DBP). Ninety-five % limits of agreements were [-29.8, 36.0 mmHg] and [-23.9, 63.0 mmHg] for daytime and nighttime SBP. The prototype sensor was reported to be more comfortable and less disturbing during daily activities and sleep compared to the reference device during 24hABPM (Figure). Conclusions: The present study demonstrated that a general PAT-based BP model significantly overestimated 24hABPM in normotensive and hypertensive subjects. The largest discrepancy was observed during nighttime. Although the PAT-based model did not provide accurate measurements of BP, the potential of cuffless BP technology is promising due to patient acceptability.

Brain mapping: topography of neurons and their transmitters involved in various brain functions.

Use of the demanding techniques microdialysis or push-pull superfusion makes it possible to identify neurons in distinct brain areas involved in central control of peripheral functions, thus enabling brain mapping. Investigations with the push-pull superfusion technique have shown that mainly catecholaminergic neurons of the posterior and anterior hypothalamus, the locus coeruleus, and the nucleus of the solitary tract are of crucial importance for blood pressure regulation. Experimentally induced blood pressure changes also modify the release of histamine, glutamate, and taurine in the posterior hypothalamus and of serotonin in the locus coeruleus. Furthermore, histaminergic neurons of the nucleus accumbens are involved in memory, serotonergic neurons of the locus coeruleus in response to noxious stimuli, while nitric oxide of striatum has been implicated in neurotoxicity elicited by amphetamines. The involvement of several neurons in one brain function is discussed.

High sodium diet and intestinal permeability in young, healthy adults

High sodium diets (HSD) have been shown to both increase blood pressure (BP) and lead to gut dysbiosis in adults. Gut dysbiosis can increase intestinal permeability (IP), allowing for translocation of bacteria and their products into the systemic circulation. There, bacteria and their products are recognized by the immune system and can activate pro-inflammatory pathways such as TH17 in a dose dependent manner. HSD has been shown to activate those pathways and increase BP in men. However, the effect of a HSD on IP has not been explored as a potential mechanism of HSD induced BP changes. The objective of this research was to investigate if a HSD can increase IP and inflammatory markers. We hypothesized that plasma concentrations of two common biomarkers of IP, zonulin and LPS binding protein (LBP), and proinflammatory TH17 lymphocytes would increase, while anti-inflammatory Treg lymphocytes would decrease on a HSD compared to a recommended sodium diet (RSD). Twenty-seven healthy participants (15W/12M, age 24±3 yrs, BP 112±9/65±6 mmHg) underwent a 10-day HSD (6,900mg sodium/d, supplemented by salt pills) and a 10-day RSD (2,300 mg sodium/d) intervention in randomized order. On day 9 of each intervention, participants collected urine and wore an ambulatory BP monitor for 24hr. Blood was collected to measure plasma zonulin and LBP by ELISA. TH17 and Treg populations were characterized from PBMCs by flow cytometry. Paired t-tests were used to compare variables on day 9 between diets. Pearson correlations were used to assess the relation between markers of IP and BP. Twenty-four-hour sodium excretion was increased on the HSD (RSD: 135±57 mmol/24h, HSD: 290±68 mmol/24h, p<0.0001). Mean 24-hr SBP (RSD: 116±10, HSD: 117±11 p=0.70) and DBP (RSD: 66±6 mmHg, HSD: 66±5 mmHg, p=0.84) were not different between diets. Plasma zonulin concentrations (RSD: 2.6±1.6 ng/ml, HSD: 2.6±1.5 ng/ml p=0.88) and LBP concentrations (RSD: 3.2±1.7 μg/ml, HSD: 3.2±1.8 μg/ml, p=0.72) were not different between diets. The TH17/Treg ratio was not different between diets (RSD: 0.54±0.51, HSD: 0.41±0.38; p=0.21) however the ratio was inversely associated with zonulin (r=-0.57 p=0.04), and LBP (r=-0.61; p=0.012) on HSD when controlling for age and sex but not on RSD (all p>0.05). These data suggest that 10 days of a HSD did not change IP, BP or T lymphocyte populations in young, healthy individuals. However, the TH17/Treg ratio was associated with zonulin and LBP suggesting that the immune system may respond to changes in IP. Future research is needed to determine whether a HSD can affect IP and inflammation in salt sensitive populations. NIH Grants R01 HL145055 and P20GM113125 This is the full abstract presented at the American Physiology Summit 2023 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.

Food readjustment plus exercise training improves cardiovascular autonomic control and baroreflex sensitivity in high-fat diet-fed ovariectomized mice.

Despite consensus on the benefits of food readjustment and/or moderate-intensity continuous exercise in the treatment of cardiometabolic risk factors, there is little evidence of the association between these two cardiovascular risk management strategies after menopause. Thus, the objective of this study was to evaluate the effects of food readjustment and/or exercise training on metabolic, hemodynamic, autonomic, and inflammatory parameters in a model of loss of ovarian function with diet-induced obesity. Forty C57BL/6J ovariectomized mice were divided into the following groups: high-fat diet-fed - 60% lipids throughout the protocol (HF), food readjustment - 60% lipids for 5 weeks, readjusted to 10% for the next 5 weeks (FR), high-fat diet-fed undergoing moderate-intensity exercise training (HFT), and food readjustment associated with moderate-intensity exercise training (FRT). Blood glucose evaluations and oral glucose tolerance tests were performed. Blood pressure was assessed by direct intra-arterial measurement. Baroreflex sensitivity was tested using heart rate phenylephrine and sodium nitroprusside induced blood pressure changes. Cardiovascular autonomic modulation was evaluated in time and frequency domains. Inflammatory profile was evaluated by IL-6, IL-10 cytokines, and TNF-alpha measurements. Only the exercise training associated with food readjustment strategy induced improved functional capacity, body composition, metabolic parameters, inflammatory profile, and resting bradycardia, while positively changing cardiovascular autonomic modulation and increasing baroreflex sensitivity. Our findings demonstrate that the association of these strategies seems to be effective in the management of cardiometabolic risk in a model of loss of ovarian function with diet-induced obesity.

SALT-SENSITIVITY IN HEALTHY NORMOTENSIVE MEN IS ASSOCIATED WITH IMPAIRED BAROREFLEX SENSITIVITY

Objective: Blood pressure (BP) responses to Na+ intake show great variability, discriminating sodium sensitive (SS) from salt resistant (SR) individuals. The pathophysiology behind salt-sensitivity is still not fully elucidated. A pivotal role for the sympathetic nervous system to BP increase after sodium loading is suggested. Therefore, we aimed to investigate the effect of the sympathovagal balance on Na+-induced BP effects and if Na+-induced effects on sympathetic activation contribute to salt-sensitivity. Design and method: We performed a randomized cross-over study in 31 young healthy men with normal BMI and eGFR. Subjects followed both an 8-day low Na+ diet (LSD, < 50mmol/d) and high Na+ diet (HSD, > 200mmol/d), in 18 subjects the diets were extended to 14-days. SS was defined as an increase of three or more mmHg standardized measured office MAP after HSD. Cardiac-output (CO) and cross correlation baroreflex sensitivity (xBRS) were measured with continuous non-invasive finger photoplethysmography. Systemic vascular resistance (SVR) was calculated as the ratio of MAP by CO. Results: After HSD, SS men (19%) showed a mean 6.2 (±2.1 SD) mmHg increase in MAP. No absolute differences in Na+-induced effects on CO and SVR could be observed between groups. After HSD, xBRS was 34% lower in SS men compared to SR men (Fig1A). Sodium loading resulted in a mean xBRS decrease of 3.4 (±6.5 SD) ms/mmHg in SS men, whilst xBRS increased with 2.3 (±6.3 SD) ms/mmHg in SR men (p = 0.06). HSD xBRS values were significantly correlated with Na+-induced BP changes in the complete group when corrected for age and BMI (Fig1B). Conclusions: Salt-sensitivity of BP in young normotensive men seems to be predominantly driven by changes in sympathovagal balance. The significant correlation between xBRS and delta BP further suggests a continuous relation between sympathetovagal balance and salt exposure. Further studies are needed to unravel pathophysiological mechanisms underlying Na+-effects on sympathetic regulation.

Prospects for developing and implementing remote blood pressure monitoring in patients under dispensary follow-up

Recently, the use of telemedicine technologies (TMT) in the healthcare has gained great importance. TMT is one of the ways to increase the healthcare availability, including in patients with high blood pressure (BP). Office BP measurement and 24-hour BP monitoring are not accurate enough to study natural or induced BP changes over long periods of time. For the selection of antihypertensive drugs and the diagnosis of hypertension (HTN) in patients with an emotionally unstable personality type, as well as in the differential diagnosis of normotension, preHTN, BP selfmonitoring comes first. The use of BP self-monitoring for the diagnosis, selection of therapy, assessment of adherence and effectiveness of treatment of HTN is more effective with remote, socalled telemetric, dynamic BP monitoring. The article presents world experience in the effective use of dynamic remote BP monitoring using TMT.

CUFFLESS BLOOD PRESSURE DEVICES AND INCONSISTENT TRACKING OF BLOOD PRESSURE CHANGES

Objective: Single point calibration is common in cuffless blood pressure (BP) measurement devices. Consequently, they may be apt at re-assessing BP at that same calibration BP but have potential for increased error as BP changes from that calibration point. This study investigates one pulse waveform-based (BPro, HealthStats) and one pulse arrival time-based (Maisense Freescanâ) cuffless device in their tracking of BP changes as compared to that of conventional cuff-based oscillometric devices. Design and method: 14 participants had 24-hour assessment of BP using BPro and a validated cuff-based oscillometric device (BPLab, Petr Telegin). Nocturnal BP dipping as measured by both devices was compared. In a separate study, six participants had BP measured with a validated cuff-based oscillometric device (OMRONâ HEM-7121) and either the BPro (n = 3) or Freescanâ device (n = 3) before and during a 2-minute cold-pressor challenge. BP change from baseline as reported by the devices were compared. Results: Average nocturnal fall in BP (mean ± SD) as reported by the cuff-based device and BPro were -15 ± 8% and -10 ± 6% (p = 0.061), respectively, for systolic BP; -19 ± 8% and -10 ± 7% (p = 0.008), respectively, for diastolic BP. Nocturnal dipping (defined as nocturnal fall > 10% in either systolic or diastolic BP) was detected in 6 participants with the BPro device as opposed to 14 as detected with the cuff-based device. During cold-pressor challenge, Freescanâ reported a systolic BP change of -4 ± 8 mmHg compared to the cuff measured change of 12 ± 8 mmHg (p = 0.017). BPro followed a similar trend to the Freescanâ device and reported a systolic BP change of -2 ± 2 mmHg compared to the cuff measured change of 14 ± 4 mmHg (p = 0.002). Conclusions: The BPro device was able to track nocturnal dipping in some but not all participants, with significant underestimation of nocturnal dipping in diastolic BP. Cold-pressor challenge induced BP changes that were unable to be detected by the cuffless devices. Whilst single point calibration may permit a cuffless device to assess when BP returns to that calibration point, tracking of BP changes appears to be inconsistent. Further investigation is required to understand the underlying factors that contribute to this inconsistency.

Use of the Polar H10 cardiofrequencemeter and Ewing's autonomic function tests in the screening of cardiac autonomic neuropathy in type 1 diabetes mellitus in Yaoundé

Cardiac autonomic neuropathy (CAN) is one of the chronic complications of diabetes that can be detected by studying spontaneous or induced changes in heart rate and blood pressure. To investigate and characterize CAN in a group of young type 1 diabetics patients. This was a cross sectional study carrying out in Yaounde Central Hospital. We successively realize a clinical examination, rest electrocardiogram, 3 min heart rate variability measure and five Ewing's functions tests (heart rate response, orthostatic blood pressure, vasalva test, control ventilation and forearm isometric contraction) with a POLAR H10 cardiofrequencemeter. Quantitative variables were express by the mean and his standard deviation; qualitative variables were expressed using frequencies. Sixty type 1 diabetics patients (37 males and 33 females) with a sex ratio of 1.6. The mean age was 19,6 ± 4.3 years, with diabetes of duration 5.9 ± 5.1 year, a mean BMI of 21.7 ± 2.9 kg/m 2 and a mean HbA1c of 9.1 ± 3.1%. Prevalence of CAN was 86.7%. The mean heart rate at rest was 82.9 ± 14.7bpm, a systolic blood pressure of 116.8 ± 18.9 mmHg, diastolic blood pressure of 70.4 ± 11.8 mmHg. The orthostatic blood pressure response was abnormal, restrict, normal respectively for 1 (1.7%), 5 (8.3%) and 54 (90%) subjects. The orthostatic response of the heart rate was abnormal for 20% of subjects and restrict for 10%. 28.3% of subjects had an abnormal Valsalva test. We found an abnormal forearm isometric contraction for 90% of subjects. The HRV index for parasympathetic activity were down low for 93.3% while index for orthosympathetic activity were down low for 90% of subjects. CAN is frequent in type 1 diabetes patients. The five Ewing and Clarke tests are replicable in clinical practice with the H10 polar cardiofrequencemeter. Thus, developing a single standard and universal consensus for the interpretation of these tests is important for a better screening of CAN.

27 Cerebral Autoregulation Associated with Falls in Older Persons with Orthostatic Hypotension?

Abstract Background It is considered well-established that orthostatic hypotension (OH) is associated with falls, population-based studies have found that a large proportion of community-dwelling older adults fulfill the criteria for OH without experiencing falls. It is therefore postulated that older individuals with OH may only experience fall if cerebral autoregulation, which is the mechanism by which the brain blood flow is maintained constant through a autoregulatory range, is impaired. Objective To evaluate the relationship between cerebral autoregulation and OH in older individuals with and without a history of falls. Method Individuals aged 3 60 years were recruited from medical clinics, by word of mouth, and from existing research registries. Baseline sociodemographics, detailed medical history and medication history were obtained. Bilateral middle cerebral artery (MCA) blood flow were recorded using transcranial Doppler ultrasound (TCD) synchronized with non-invasive continuous blood pressure and ECG recordings. Synchronized brain blood flow signals, heart trace and blood pressure signals were first recorded during 10 minutes’ supine rest. Participants were then be asked to perform a standard set of mathematical calculations, a Valsalva maneuver and to stand up from a seated position. Results 36 participants have been evaluated to date (13 fallers, 23 non-Fallers). There is no statistically significant difference in gender, ethnicity or height and weight between groups. Fluctuations in MCA flow velocity were observed with spontaneous fluctuations in blood pressure at rest and with induced blood pressure changes during the challenge maneuvers. Visual inspection of the signals obtained suggested that changes in MCA flow velocity were more marked among fallers and non-fallers. Conclusion Synchronization of cerebral blood flow and continuous blood pressure signals opens up numerous new possibilities in research and clinical practice. Our preliminary findings suggest that cerebral autoregulation does play a role in determining the presence of symptomats in older individuals with OH.

Validation of Evans Blue inhibits Compound 48/80 induced inflammation in hypertension rat models

BackgroundHypertension (HT) is a multifactorial cardiovascular disorder involves in variety genetic and environmental factors, and it is a major risk factor for cardiovascular disease. In order to study the pathophysiology of HT, the proper robust and reproducible experimental animal models are required. Phase‐1 hypertension (P1‐HT) is the beginning stage of high blood pressure (BP). The ideal P1‐HT animal model should have human‐like cardiovascular anatomy, hemodynamics, and physiology that includes genetic and non‐genetic models. Moreover, inflammation responses may cause plasma leakage and affect BT readings in experimental animals. Among current HT rat models, Spontaneously Hypertensive Rats (SHR) with both neural and vascular alterations is the most commonly used genetic HT animal model. In this study, we investigated inflammatory mediators' effects and responses in correlation with BP readings among current commercial available SD/SHR rats and our new breeding P1‐HT rat to further calibrating BP readings in variety rat HT models.MethodsHistamine, Capsaicin, Compound 48/80 or Substance P were administered into the femoral vein of rats individually to induce inflammation and vascular dysfunction. Then we analyzed mean arterial pressure (MAP) and analyze plasma extravasation using Evans Blue dye. One Way ANOVA with Bonferroni correction and linear regression were used for statistics. Statistical significances were set at a P< 0.05.ResultsOur data showed significant negative linear regression on the degree of plasma extravasation with BP changes in substance P induced neurogenic inflammation but positive linear regression in compound 48/80 induced immunogenic inflammation. In addition, pretreated with Evans blue dye could inhibit compound 48/80 induced extensive plasma extravasation, mast cell degranulation, and edema significantly. In addition, our data show significant variation BP readings among neurogenic and immunogenic inflammation induced BP changes in different rat HT models.ConclusionOur data shows for the first time that methodical variations observed among normal and hypertensive animals, can potentially translate into differential BP patterns, which can be falsely taken to generate significant biological bias. Our study therefore highlights the pivotal need in interpretation of BP data using different HT rat models in the study.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pulse Transit Time Based Continuous Cuffless Blood Pressure Estimation: A New Extension and A Comprehensive Evaluation

Cuffless technique enables continuous blood pressure (BP) measurement in an unobtrusive manner, and thus has the potential to revolutionize the conventional cuff-based approaches. This study extends the pulse transit time (PTT) based cuffless BP measurement method by introducing a new indicator – the photoplethysmogram (PPG) intensity ratio (PIR). The performance of the models with PTT and PIR was comprehensively evaluated in comparison with six models that are based on sole PTT. The validation conducted on 33 subjects with and without hypertension, at rest and under various maneuvers with induced BP changes, and over an extended calibration interval, respectively. The results showed that, comparing to the PTT models, the proposed methods achieved better accuracy on each subject group at rest state and over 24 hours calibration interval. Although the BP estimation errors under dynamic maneuvers and over extended calibration interval were significantly increased for all methods, the proposed methods still outperformed the compared methods in the latter situation. These findings suggest that additional BP-related indicator other than PTT has added value for improving the accuracy of cuffless BP measurement. This study also offers insights into future research in cuffless BP measurement for tracking dynamic BP changes and over extended periods of time.

Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis.

Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients. The healthy volunteers underwent a 4-h intravenous infusion of LPS (total dose: 2ngkg-1 ). Mean arterial blood pressure (MAP, arterial transducer) and middle cerebral artery blood flow velocity (MCAv, transcranial Doppler ultrasound) were recorded continuously during thigh-cuff deflation-induced changes in MAP for the determination of a modified rate of regulation (RoR). This was performed before and after LPS infusion in healthy volunteers, and within 72h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh-cuff deflation caused a MAP reduction of 16 (13-20) % at baseline and 18 (16-20) % after LPS, while the MAP reduction was 12 (11-13) % in patients (P<0·05 versus volunteers at baseline; P<0·01 versus volunteers after LPS). The corresponding RoR values increased from 0·46 (0·31-0·49) s-1 at baseline to 0·58 (0·36-0·74) s-1 after LPS (P<0·05) in healthy volunteers, whereas they were similar to values observed in patients [0·43 (0·36-0·52) s-1 ; P=0·91 versus baseline; P=0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh-cuff deflation failed to induce sufficient MAP reductions in patients.

Passive leg raising induced-changes in blood pressure predict fluid responsiveness following cardiac surgery

Passive leg raising induced-changes in blood pressure predict fluid responsiveness following cardiac surgery

Does Stroke Subtype and Measurement Technique Influence Estimation of Cerebral Autoregulation in Acute Ischaemic Stroke?

Background: It is known that dynamic cerebral autoregulation (dCA) is acutely impaired following ischaemic stroke (IS). However, the influence of stroke subtype, the affected (AF) and unaffected (UA) hemispheres, and the effects of a methodological approach on dCA estimates in stroke are all inconclusive. Therefore, we studied cortical and subcortical acute IS (AIS) patients to test the primary hypotheses that (1) dCA is impaired in stroke subtypes when compared to controls, (2) dCA impairment is more pronounced in the AF compared with the UA hemisphere, and (3) similar results are obtained with both spontaneous blood pressure (BP) fluctuation techniques, and sudden induced BP changes by thigh cuff deflation. Methods: We assessed the dCA values in AIS patients and in healthy controls (n = 10). The AIS patient group consisted of anterior circulation cortical (n = 11) and subcortical (n = 11) strokes within 48 h of symptom onset. Cerebral blood flow velocity was measured using transcranial Doppler ultrasound, and BP measurements were recorded before, during and after the release of bilateral thigh cuffs in 10 controls (7 males) of a mean age of 59 ±15 years (range 31-75), 11 cortical strokes (7 males) of a mean of age 65 ± 19 years (range 25-88) and 11 subcortical strokes (7 males) of a mean age of 60 ± 18 years (range 39-85). Autoregulation index (ARI) estimates, calculated using spontaneous fluctuations and thigh cuff manoeuvre, were derived. Differences in ARI (Tiecks' model) were tested with repeated-measures ANOVA. Results: A total of 22 patients were included, comprising 11 subcortical (lacunar clinical syndrome) and 11 cortical strokes (total anterior circulation stroke/partial anterior circulation syndrome). Of the 10 control subjects, 1 later withdrew because of intolerance to the thigh cuffs. Similar ARI estimates were obtained in both groups, whether assessed from spontaneous fluctuations or thigh cuff measurements (p = 0.37). ARI differences were not significantly different between hemispheres for both control and stroke populations. ARI was significantly impaired in AIS patients compared to age-, sex- and BP-matched control subjects, with a greater impairment of dCA observed in cortical IS. Conclusions: The results of this study suggest that both spontaneous fluctuations and thigh cuff deflation techniques are able to provide reliable estimates of ARI, with the estimates from both spontaneous fluctuations and thigh cuff deflation techniques being in keeping with those reported elsewhere in the literature. dCA was impaired following AIS compared to controls when stroke subtype was considered. Importantly, no differences were observed between UA and AF. This has implications for the assessment of CA after stroke and reinforces the need to define a ‘gold standard' test for the investigation of CA.

Noninvasive Measurement of Cerebral Blood Flow and Blood Oxygenation Using Near-Infrared and Diffuse Correlation Spectroscopies in Critically Brain-Injured Adults

This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation. Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBF(DCS)), and changes in oxy-hemoglobin (DeltaHbO(2)), deoxy-hemoglobin (DeltaHb), and total hemoglobin concentration (DeltaTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBF(XeCT)) and were then compared to rCBF(DCS). Spearman's rank coefficients were employed to test for associations between rCBF(DCS) and rCBF(XeCT), as well as between rCBF from both modalities and NIRS parameters. rCBF(DCS) and rCBF(XeCT) showed good correlation (r (s) = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBF(DCS) and DeltaHbO(2)/DeltaTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients. DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.

Cerebrovascular Regulation in the Postural Orthostatic Tachycardia Syndrome (POTS)

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cere brovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vaso · regulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing ABFV to ΔΒΡ during head-up tilt. A number of dynamic methods, relating ABFV to ΔΒΡ during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Val salva maneuver. The ABFV to ΔΒΡ provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an in־ creased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS).

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Estimation of baroreflex sensitivity using transfer function analysis: normal values and theoretical considerations.

Human baroreflex sensitivity is traditionally derived from changes in heart rate due to alterations of the baroreceptor input (pharmacologically or physically induced blood pressure changes). Transfer function analysis (TFA) of changes in heart rate (output function) and physiological blood pressure oscillations (input function) at approximately 0.1 Hz (Mayer waves) has already been accepted as a measure of baroreflex sensitivity (BRS). Transfer function analysis provides gain and phase shift values for each frequency band and body position. We performed TFA in 50 normal subjects in the supine and tilted positions, at mid-frequency (0.05-0.15 Hz) and high-frequency (0.15-0.33 Hz) bands, recording heart rate and blood pressure continuously with a Finapres device. Gain values were in accordance with previous studies. Phase shifts lay within a narrow range for all frequency bands and positions. High correlations were found between phase shifts of the same frequency band, but not for those of the same position. This supports the idea that the transfer mechanisms for the two frequency bands may, in part, be different. There was a poor correlation between gain and phase values on the one hand and, on the other hand, further spectral measures and the results of standard autonomic tests. This suggests that TFA may not only be a measure of BRS, but also a complementary tool for evaluation of autonomic function.

Serotonin outflow in the hypothalamus of conscious rats: origin and possible involvement in cardiovascular control

The push-pull technique was used to investigate the effects of neuroactive compounds and experimentally induced blood pressure changes on the release of endogenous serotonin in the posterior hypothalamic area of the rat. Hypothalamic superfusion with artificial cerebrospinal fluid which contained 80 mM K + or 1 μM veratridine enhanced the rate of serotonin release. Superfusion with tetrodotoxin (5 μM) led to a pronounced decrease in the serotonin release rate. Increases in blood pressure elicited by intravenous infusions of noradrenaline (3–4 μg/kg/min) or phenylephrine (10 μg/kg/min) enhanced the release of serotonin in the hypothalamus. Similarly, the serotonin release rate was enhanced by hypervolaemia. Decreases in blood pressure elicited by intravenous administration of nitroprusside (30–40 μg/kg/min) or chlorisondamine (3 mg/kg) reduced the release of serotonin. Likewise, the serotonin release rate was decreased by hypovolaemia. With one exception (hypothalamic superfusion with tetrodotoxin) neither neuroactive drugs, nor experimentally elicited blood pressure changes modified the release rate of the metabolite 5-hydroxyindoleacetic acid (5-HIAA). These findings show that changes in blood pressure lead to counteractive alterations in the release of serotonin. Thus, serotoninergic neurons of the posterior hypothalamus seem to be involved in the homeostasis of blood pressure by exerting a hypotensive function. At least in the hypothalamus, the concentration of 5-HIAA in the superfusate does not seem to be a reliable marker for the activity of serotoninergic neurons.