Measured Mean Arterial Pressure Research Articles

Effectiveness of the First Trimester Samrakshan Protocol for the Identification of Pregnant Women at High Risk for Preterm Pre-eclampsia.

Aim To determine the effectiveness of the first trimester Samrakshan protocol for the identification of pregnant women at high risk for preterm pre-eclampsia (PE). Methods Samrakshan uses a protocol that integrates routine first-trimester ultrasound assessment at 11 to 14 gestation weeks with the measurement of mean arterial blood pressure and mean uterine artery pulsatility index assessment to determine a customized risk for preterm PE and fetal growth restriction. Based on the risk assessment, pregnant women are classified as high or low risk. Results The protocol had a high specificity (90.4%, 95% CI: 89.4%, 91.2%) and negative predictive value (98.1%, 95% CI: 97.6%, 99%) for preterm PE. The odds ratio and positive likelihood ratio for preterm PE were 16.7 (95% CI: 12.3, 22.6) and 6.64 (95% CI: 5.77, 7.63), respectively. Conclusions The positive likelihood ratio and odds ratios indicate that pregnant women identified as high risk for preterm PE using the first-trimester protocol of Samrakshan are significantly more likely to develop preterm PE than low-risk women.

Arterial site selection for measurement of mean arterial pressure in septic shock patients on high-dose norepinephrine.

The guidelines of the Surviving Sepsis Campaign suggest using invasive blood pressure (IBP) measurement in septic shock patients, without specifying for a preferred arterial site for accuracy in relation to the severity of septic shock. The objective of this study was to determine the mean arterial pressure (MAP) gradient between the femoral and radial artery sites in septic shock patients. This prospective study was carried out at a 20-bed ICU in a university hospital. Simultaneous MAP measurements at femoral and radial arterial sites were obtained in septic shock patients receiving norepinephrine (≥0.1 μg/kg/min), with a pre-planned subgroup analysis for those receiving a high dose of norepinephrine (≥0.3 μg/kg/min). The median norepinephrine dose across all 80 patients studied, including 59 patients on a high dose, was 0.4 (0.28-0.7) μg/kg/min. Overall, simultaneous measurement of MAP (mmHg) at the femoral and radial arterial sites produced mean (95% CI) MAP values of 81 (79-83) and 78 (76-80), respectively, with a mean difference of 3.3 (2.67-3.93), p < 0.001. In Bland-Altman analysis of MAP measurements, the detected effect sizes were 1.14 and 1.04 for the overall and high-dose cohorts, respectively, which indicates a significant difference between the measurements taken at each of the two arterial sites. The Pearson correlation coefficient indicated a weak but statistically significant correlation between MAP gradient and norepinephrine dose among patients receiving a high dose of norepinephrine (r = 0.289; p = 0.026; 95% CI 0.036-0.508). In septic shock patients, MAP readings were higher at the femoral site than at the radial site, particularly in those receiving a high dose of norepinephrine. [ClinicalTrials.gov], identifier [NCT03475667].

Cerebral vascular function following the acute consumption of caffeinated artificially- and sugar sweetened soft drinks in healthy adults.

Chronic consumption of sugar- and artificially-sweetened beverages (SSB and ASB) are associated with an increased risk of stroke but it is unclear how acute consumption influences cerebral vascular function. Purpose: We hypothesized that: (1) acute consumption of SSB and ASB would augment dynamic cerebral autoregulation (dCA) and attenuate cerebral vascular reactivity to hypercapnia (CVRCO2) compared to water; and (2) dCA and CVRCO2 would be attenuated with SSB compared to ASB and water. Methods: Twelve healthy adults (age: 23 ± 2 years, four females) completed three randomized trials where they drank 500 ml of water, SSB (Mountain Dew®), or ASB (Diet Mountain Dew®). We measured mean arterial pressure (MAP), middle and posterior cerebral artery blood velocities (MCAv and PCAv), and end-tidal CO2 tension (PETCO2). Cerebral vascular conductance was calculated as cerebral artery blood velocity/MAP (MCAc and PCAc). Twenty min after consumption, participants completed a 5 min baseline, and in a counterbalanced order, a CVRCO2 test (3%, 5%, and 7% CO2 in 3 min stages) and a dCA test (squat-stand tests at 0.10 Hz and 0.05 Hz for 5 min each) separated by 10 min. CVRCO2 was calculated as the slope of the linear regression lines of MCAv and PCAv vs. PETCO2. dCA was assessed in the MCA using transfer function analysis. Coherence, gain, and phase were determined in the low frequency (LF; 0.07-0.2 Hz) and very low frequency (VLF; 0.02-0.07 Hz). Results: MCAv and MCAc were lower after SSB (54.11 ± 12.28 cm/s, 0.58 ± 0.15 cm/s/mmHg) and ASB (51.07 ± 9.35 cm/s, 0.52 ± 1.0 cm/s/mmHg) vs. water (62.73 ± 12.96 cm/s, 0.67 ± 0.11 cm/s/mmHg; all P < 0.035), respectively. PCAc was also lower with the ASB compared to water (P = 0.007). MCA CVRCO2 was lower following ASB (1.55 ± 0.38 cm/s/mmHg) vs. water (2.00 ± 0.57 cm/s/mmHg; P = 0.011) but not after SSB (1.90 ± 0.67 cm/s/mmHg; P = 0.593). PCA CVRCO2 did not differ between beverages (P > 0.853). There were no differences between beverages for coherence (P ≥ 0.295), gain (P ≥ 0.058), or phase (P ≥ 0.084) for either frequency. Discussion: Acute consumption of caffeinated SSB and ASB resulted in lower intracranial artery blood velocity and conductance but had a minimal effect on cerebral vascular function as only MCA CVRCO2 was altered with the ASB compared to water.

First-trimester preterm preeclampsia prediction with metabolite biomarkers: differential prediction according to maternal body mass index

Prediction of preeclampsia risk is key to informing effective maternal care. Current screening for preeclampsia at 11 to 13 weeks of gestation using maternal demographic characteristics and medical history with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor can identify approximately 75% of women who develop preterm preeclampsia with delivery at <37 weeks of gestation. Further improvements to preeclampsia screening tests will likely require integrating additional biomarkers. Recent research suggests the existence of distinct maternal risk profiles. Therefore, biomarker evaluation should account for the possibility that a biomarker only predicts preeclampsia in a specific maternal phenotype. This study aimed to verify metabolite biomarkers as preterm preeclampsia predictors early in pregnancy in all women and across body mass index groups. Observational case-control study drawn from a large prospective study on the early prediction of pregnancy complications in women attending their routine first hospital visit at King's College Hospital, London, United Kingdom, in 2010 to 2015. Pregnant women underwent a complete first-trimester assessment, including the collection of blood samples for biobanking. In 11- to 13-week plasma samples of 2501 singleton pregnancies, the levels of preselected metabolites implicated in the prediction of pregnancy complications were analyzed using a targeted liquid chromatography-mass spectrometry method, yielding high-quality quantification data on 50 metabolites. The ratios of amino acid levels involved in arginine biosynthesis and nitric oxide synthase pathways were added to the list of biomarkers. Placental growth factor and pregnancy-associated plasma protein A were also available for all study subjects, serving as comparator risk predictors. Data on 1635 control and 106 pregnancies complicated by preterm preeclampsia were considered for this analysis, normalized using multiples of medians. Prediction analyses were performed across the following patient strata: all subjects and the body mass index classes of <25, 25 to <30, and ≥30 kg/m2. Adjusted median levels were compared between cases and controls and between each body mass index class group. Odds ratios and 95% confidence intervals were calculated at the mean ±1 standard deviation to gauge clinical prediction merits. The levels of 13 metabolites were associated with preterm preeclampsia in the entire study population (P<.05) with particularly significant (P<.01) associations found for 6 of them, namely, 2-hydroxy-(2/3)-methylbutyric acid, 25-hydroxyvitamin D3, 2-hydroxybutyric acid, alanine, dodecanoylcarnitine, and 1-(1Z-octadecenyl)-2-oleoyl-sn-glycero-3-phosphocholine. Fold changes in 7 amino acid ratios, all involving glutamine or ornithine, were also significantly different between cases and controls (P<.01). The predictive performance of some metabolites and ratios differed according to body mass index classification; for example, ornithine (P<.001) and several ornithine-related ratios (P<.0001 to P<.01) were only strongly associated with preterm preeclampsia in the body mass index of <25 kg/m2 group, whereas dodecanoylcarnitine and 3 glutamine ratios were particularly predictive in the body mass index of ≥30 kg/m2 group (P<.01). Single metabolites and ratios of amino acids related to arginine bioavailability and nitric oxide synthase pathways were associated with preterm preeclampsia risk at 11 to 13 weeks of gestation. Differential prediction was observed according to body mass index classes, supporting the existence of distinct maternal risk profiles. Future studies in preeclampsia prediction should account for the possibility of different maternal risk profiles to improve etiologic and prognostic understanding and, ultimately, clinical utility of screening tests.

Effects of intrarenal angiotensin 1-7 infusion on renal haemodynamic and excretory function in anaesthetised two-kidney one-clip and deoxycorticosterone acetate-salt hypertensive rats.

What is the central question of this study? Are renal functional responses to intrarenal angiotensin 1-7 (Ang (1-7)) infusion dependent on the level of the endogenous renin-angiotensin system (RAS) in the two-kidney one-clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt animal models of hypertension? What is the main finding and its importance? The renal actions of Ang (1-7) are dependent on the relative endogenous levels of each arm of the classical angiotensin II-angiotensin II type 1 receptor (AT1 R) axis and those of the Ang (1-7)-Mas receptor axis. These findings support the hypothesis that a balance exists between the intrarenal classical and novel arms of the RAS, and in particular the relative abundance of AT1 R to Mas receptor, which may to a large extent determine the renal excretory response to Ang (1-7) infusion. This study investigated the action of angiotensin 1-7 (Ang (1-7)) on renal haemodynamic and excretory function in the two-kidney one-clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt rat models of hypertension, in which the endogenous renin-angiotensin system (RAS) activity was likely to be raised or lowered, respectively. Rats were anaesthetised and prepared for the measurement of mean arterial pressure and kidney function during renal interstitial infusion of Ang (1-7) or saline. Kidney tissue concentrations of angiotensin II (Ang II) and Ang (1-7) were determined. Intrarenal infusion of Ang (1-7) into the clipped kidney of 2K1C rats increased urine flow (UV), absolute (UNa V) and fractional sodium (FENa ) excretions by 110%, 214% and 147%, respectively. Renal Ang II concentrations of the clipped kidney were increased with no major changes in Ang (1-7) concentration. By contrast, Ang (1-7) infusion decreased UV, UNa V, and FENa by 27%, 24% and 21%, respectively in the non-clipped kidney in which tissue Ang (1-7) concentrations were increased, but renal Ang II concentrations were unchanged compared to sham animals. Ang (1-7) infusion in DOCA-salt rats had minimal effects on glomerular filtration rate but significantly decreased UV, UNa V and FENa by ∼30%. Renal Ang (1-7) concentrations were higher and Ang II concentrations were lower in DOCA-salt rats compared to sham rats. These findings demonstrate that the intrarenal infusion of exogenous Ang (1-7) elicits different renal excretory responses the magnitude of which is dependent on the balance between the endogenous renal Ang II-AT1 receptor axis and Ang (1-7)-Mas receptor axis.

MicroRNA-195a-5p Regulates Blood Pressure by Inhibiting NKCC2A.

Previous studies showed that miR-195a-5p was among the most abundant microRNAs (miRNAs) expressed in the kidney. Lentivirus silencing of tumor necrosis factor-α (TNF) was performed in vivo and in vitro. Luciferase reporter assays confirmed that bumetanide-sensitive Na+-K+-2Cl- cotransporter isoform A (NKCC2A) mRNA is targeted and repressed by miR-195a-5p. Radiotelemetry was used to measure mean arterial pressure. TNF upregulates mmu-miR-195a-5p, and -203 and downregulates mmu-miR-30c and -100 in the medullary thick ascending limb of male mice. miR-195a-5p was >3-fold higher in the renal outer medulla of mice given an intrarenal injection of murine recombinant TNF, whereas silencing TNF inhibited miR-195a-5p expression by ≈51%. Transient transfection of a miR-195a-5p mimic into medullary thick ascending limb cells suppressed NKCC2A mRNA by ≈83%, whereas transfection with Anti-miR-195a-5p increased NKCC2A mRNA. Silencing TNF in medullary thick ascending limb cells prevented increases in miR-195 induced by 400 mosmol/kg H2O medium, an effect reversed by transfection with a miR-195a-5p mimic. Expression of phosphorylated NKCC2 increased 1.5-fold in medullary thick ascending limb cells transfected with Anti-miR-195a-5p and a miR-195a-5p mimic prevented the increase, which was induced by silencing TNF in cells exposed to 400 mosmol/kg H2O medium after osmolality was increased by adding NaCl. Intrarenal injection of TNF suppressed NKCC2A mRNA, whereas injection of miR-195a-5p prevented the increase of NKCC2A mRNA abundance and phosphorylated NKCC2 expression when TNF was silenced. Intrarenal injection with miR-195a-5p markedly attenuated MAP after renal silencing of TNF in mice given 1% NaCl. The study identifies miR-195a-5p as a salt-sensitive and TNF-inducible miRNA that attenuates NaCl-mediated increases in blood pressure by inhibiting NKCC2A.

The Implementation of Preeclampsia Screening and Prevention (IMPRESS) Study

Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of perinatal morbidity and mortality worldwide. Despite strong evidence that the combination of systematic preeclampsia screening based on the Fetal Medicine Foundation preeclampsia risk calculation algorithm with treatment of high-risk patients with low-dose aspirin reduces the incidence of preterm preeclampsia more than currently used risk-factor-based screening, real-world implementation studies have not yet been done in Canada. This study aimed to assess the operational feasibility of implementing first-trimester screening and prevention of preterm preeclampsia (<37 weeks) alongside a publicly funded first-trimester combined screening program for aneuploidies. This was a prospective implementation study. Consecutive pregnant patients referred for first-trimester combined screening (11-13+6 weeks) were offered screening for preeclampsia based on the Fetal Medicine Foundation algorithm concomitantly with their aneuploidy screen. Consenting participants were screened using maternal risk factors, mean arterial pressure, uterine artery Doppler pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor. Risk for preterm preeclampsia (<37 weeks) was calculated using the Fetal Medicine Foundation algorithm, and individuals with a risk score ≥1 per 100 were recommended to use aspirin (162 mg once daily at bedtime, <16-36 weeks). Implementation metrics assessed included: acceptability, operational impact, proportion of aspirin initiation, quality and safety measures, and screen performance. Between December 1, 2020 and April 23, 2021, 1124 patients consented to preeclampsia screening (98.3% uptake), and 92 (8.2%) screened positive. Appointments for patients receiving first-trimester combined screening aneuploidy and preeclampsia screening averaged 6 minutes longer than first-trimester combined screening alone, and adding uterine artery Doppler pulsatility index averaged 2 minutes. Of the 92 patients who screened as high-risk for preeclampsia, 72 (78.3%) were successfully contacted before 16 weeks' gestation. Of these, 62 (86.1%) initiated aspirin, and 10 (13.9%) did not. Performance audit identified a consistent negative bias with mean arterial pressure measurements (median multiple of the median <1 in 10%); other variables were satisfactory. There were 7 cases of preterm preeclampsia (0.69%): 5 and 2 in the high- and low-risk groups, respectively. Screening detected 5 of 7 (71.4 %) preterm preeclampsia cases, with improved performance after adjustment for aspirin treatment effect. This study confirms the operational feasibility of implementing an evidence-based preeclampsia screening and prevention program in a publicly funded Canadian setting. This will facilitate implementation into clinical service and the scaling up of this program at a regional and provincial level.

ODP238 RELATIONSHIP BETWEEN BODY COMPOSITION, POST PRANDIAL GLUCOSE AND INSULIN FOR EARLY PREDICTION OF TYPE 2 DIABETES AND CARDIOVASCULAR RISK.

Abstract Different studies report that visceral fat percentage, visceral adiposity index (VAI) and body mass index (BMI) are considered markers of dysfunction and adipose tissue distribution, which are considered early detection tools and indirect expression of cardio metabolic risk; however it is also reported that post prandial glucose and insulin are abnormalities that detect early type 2 diabetes and cardiovascular risk, due to their toxic effect on the vascular endothelium. The objective of the research was to evaluate the association of body composition, glucose and insulin postprandial for early prediction of diabetes and cardiovascular risk. It is a non-experimental study of cross-sectional design, in a total population of 271 adults between the ages 19 and 65 years, without diabetes, in a non-random sample calculated with 95% confidence level of patients attending outpatient clinics of private and IESS hospitals of Riobamba. Descriptive statistics were performed for all variables. With the variables related to cardio metabolic risk such as age, sex, abdominal circumference, mean arterial pressure, BMI, visceral fat and biochemical measures of HbA1c, fasting glucose, postprandial glucose and insulin, HOMA-IR index, and HDLC, triglycerides, cardio vascular risk index given by the ratio triglycerides/HDLc cholesterol over 3.5. These variables were grouped by a multivariate cluster analysis, kmeans, and two homogeneous groups were obtained, different from each other and different from the others, and then the average cardiovascular risk in each group was calculated. A 9: 1 ratio of women/men was found, for cluster 1 the average age was 49, and in cluster 2 it was 48 years, TAM: 87.5 mmHg, BMI: 27.12, PAB: 109 cm, visceral fat 12.79 and cardiovascular risk 4.78. In group 2 with predominance in cluster 2 the average values of the variables studied were significantly higher with a statistically significant p value for the differences between groups of postprandial glucose and insulin (p less than 0. 05). Conclusions postprandial glucose and insulin are early predictors of cardiovascular risk and diabetes. Key words: postprandial glucose, postprandial insulin, cardiovascular risk, body composition. Presentation: No date and time listed

Abstract 032: Afferent Renal Denervation And IL-1 Receptor Blockade Attenuate The Pathogenesis Of Hypertension In DOCA-salt Mice Similarly: Evidence For A Common Mechanism?

Emerging evidence suggests an interaction between renal inflammation and afferent renal nerves in some preclinical models of hypertension. In this study we tested the hypothesis that the inflammatory cytokine IL-1β interacts with afferent renal nerves in the pathogenesis of the DOCA-salt mouse model of hypertension. Specifically, we compared the effect of total renal denervation (TRDN) and afferent RDN (ARDN) on the development of DOCA-salt hypertension to that observed in animals receiving the IL-1 receptor antagonist anakinra. In the first study , 10-week-old male C57BL6/J mice were implanted with radiotelemeters for measurement of mean arterial pressure (MAP). DOCA was administered via subcutaneous pellet containing 50 mg of DOCA, controls received a drug free pellet. Uni-nephrectomy, pellet insertion, salt treatment, TRDN, ARDN, or sham denervation were all performed on the same day. TRDN and ARDN was performed through peri-axonal application of phenol and capsaicin respectively. In the second study , the IL-1 receptor antagonist anakinra (75mg/kg) or vehicle control (0.9% saline) was delivered via intraperitoneal injection daily 10 days post-induction of hypertension. Renal cytokine protein was quantified by Multiplex ELISA. All values reported are mean + SEM, all groups n=5. In the first study , MAP increased in sham treated DOCA-salt mice +43 ± 1 mmHg from baseline by the end of the 3 rd week of DOCA-salt. This response was attenuated by 40% in TRDN (+26 ± 4 mmHg) and by 44% in ARDN DOCA-salt mice (+24 ± 3 mmHg). IL-1β was increased in DOCA-salt kidneys (2.1 ± 0.4 pg/mg) compared to control kidneys (0.36 ± 0.1 pg/mg). In the second study , anakinra similarly attenuated the increase in MAP by 45% (+21 ± 2 mmHg) compared to vehicle controls (+38 ± 1 mmHg). Neither ARDN nor IL-1 receptor antagonism had any effect on renal inflammatory cytokines IL-1β, IL-6, or TNFα. The comparable attenuation in the MAP response to DOCA-salt ARDN and anakinra treated groups as well as the unchanged inflammatory phenotype is consistent with a common mechanism of action. We hypothesize that intrarenal IL-1β activates sympathoexcitatory renal afferent nerves to increase MAP in DOCA-salt mice. Future studies are needed to directly test this hypothesis.

Abstract 120: Midgestation Eplerenone Treatment Ablates Leptin-induced Hypertension And Endothelial Dysfunction But Not Fetal Growth Restriction In Preeclamptic Mice

Elevated leptin (lep) in pregnant women strongly associates with preeclampsia (PE), a hypertensive pregnancy disorder. Our lab established a mid-late gestation lep-infusion model of PE, which induces endothelial dysfunction, hypertension and fetal growth restriction (FGR); deletion of endothelial mineralocorticoid receptors (MR) ablated these PE characteristics in pregnant mice. Whether pharmacological MR antagonism ablates lep-induced PE, however, is unknown. We hypothesized that MR antagonism (eplerenone) ablates lep-induced PE characteristics in pregnant mice. We infused pregnant BALB/c mice with leptin (lep, 0.9mg/kg/day) or saline (sham) via osmotic minipump alongside eplerenone (Eplr, 200mg/kg/day) or vehicle in drinking water from gestation day (GD)11-18. We measured vascular function via wire myography of 2 nd order mesenteric vessels and pup/placental weights on GD18 (n=5-7). We implanted radiotelemeters in separate mice (n=1-3) prior to mating and measured mean arterial pressure (BP) from GD11-18. Pre-pregnancy BP did not differ between treatment groups. Preliminary data indicates lep increased BP compared to sham from GD11-18 (112.7±4.5 lep vs 89.4 sham mmHg,) and Eplr decreased BP in lep pregnant mice (97.2±7.2 lep+Eplr mmHg, P=0.09 vs lep student’s t-test). Vascular relaxation to endothelial-dependent acetylcholine (ACh) decreased in lep+vehicle compared to sham+vehicle (*P&lt;0.05, 2-Way ANOVA w/ RM). Eplr+lep restored ACh-mediated vascular relaxation (*P&lt;0.05 vs lep+vehicle). LNAME pre-incubation did not ablate differences in ACh-mediated relaxation between lep+vehicle and lep+eplr (P&gt;0.05) indicating that Eplr restored a non-NO mechanism to improve endothelial function. Lep as a variable decreased pup weight in both vehicle and Eplr pregnant mice, however, Eplr did not increase pup weight in either vehicle or lep mice (0.74±0.01sham+veh, 0.71±0.01 lep+veh, 0.70±0.01 sham+eplr, 0.67±0.01 lep+eplr (g), *P&lt;0.05, 2-Way ANOVA). Collectively these data indicate that Eplr improves lep-induced endothelial dysfunction and hypertension, but may not prevent FGR when given from GD11-18. Therefore, further studies will determine whether MR antagonism promises therapeutic potential in lep-induced PE.

Abstract P048: Western Diet Consumption Exacerbates Hypertension In Hyperandrogenemic Female Rat, A Model Of Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome ( PCOS ) is the most common endocrinopathy affecting women of reproductive age. It is characterized by hyperandrogenemia, increased blood pressure ( BP ) and metabolic dysfunction. Consumption of western diet ( WD ) aggravates the reproductive and metabolic phenotypes of PCOS. Yet, the effect of WD consumption on BP in PCOS women is not clear. Therefore, this study was undertaken to test the hypothesis that WD consumption in hyperandrogenemic female ( HAF ) rats (a model that mimics most of PCOS symptoms) increases BP along with increasing renal expression of the vasoconstrictor ( VC ) components of the renin-angiotensin system ( RAS ). Methods: At 4 wks of age, female Sprague Dawley rats were implanted (s.c.) with either 5α-dihydrotestosterone pellets (7.5 mg/90 d; HAF rats) or placebo pellets (controls; CON) , that were replaced throughout life. At 4 wks of age, HAF and CON rats were also started on WD (high fat and high sucrose content) or control diet ( CD ), thus forming 4 groups; CON-CD, CON-WD, HAF-CD and HAF-WD. At 20 wks of age, rats were implanted with radiotelemetry transmitters in the abdominal aorta to measure mean arterial pressure ( MAP ) [n=4-5/group]. Another set of rats (n=3-6/group) were euthanized and kidneys collected for measurement of components of the RAS by western blot. Results: are shown in Table 1 . Conclusion: WD consumption in HAF results in further increases in BP, despite upregulation of components of the intrarenal vasodilator RAS (ACE2 and AT2R), which is likely a protective mechanism. Future studies will determine the role(s) of other major VC pathways (e.g. endothelin system) in hypertension in WD-fed HAFs.

The Time-course Of Blood Pressure Change In Adults During Prolonged Sitting: A Three-level Meta-analysis

PURPOSE: Acute bouts of prolonged sitting have been found to detrimentally impact the cardiovascular system, including acute increases in blood pressure (BP). Repeated increases in BP can damage the heart and blood vessels. While the responses to prolonged sitting have been reported independently in many studies, a multi-level meta-analysis that can consider non-independence of measurements and effect sizes of blood pressure change during prolonged sitting has not been explored. Therefore, we conducted a meta-analysis to track BP change during prolonged sitting. METHODS: Four databases were searched through September 2021. Inclusion criteria were sitting trials > 1 hour, adults (>18 years old), and brachial measurements of either mean arterial pressure (MAP), systolic BP (SBP), diastolic BP (DBP) obtained at more than two time points. Trials with standing, aerobic-, or simple resistance interruption strategies were included and analyzed separately. A random-effects 3-level meta-analysis was conducted to account for the interdependence of multiple data points from the same participants and the same trials. RESULTS: Thirty-one articles (36 trials, n = 572) met inclusion criteria. Prolonged uninterrupted sitting resulted in significant increases of all BP indices; MAP (ꞵ = 0.60 mmHg/hr, 95% CI: 0.18, 1.02, p = 0.004), SBP (ꞵ = 0.60 mmHg/hr, 95% CI: 0.30, 0.90, p < 0.001), and DBP (ꞵ = 0.48 mmHg/hr, 95% CI: 0.18, 0.72, p < 0.001). In trials where sitting was interrupted, there were non-significant effects of time on MAP (ꞵ = 0.06 mmHg/hour, 95% CI: -0.24, 0.36, p = 0.750), and small significant decreases in SBP (ꞵ = -0.24 mmHg/hr, 95% CI: -0.42, -0.06, p = 0.018) and DBP (ꞵ = -0.24 mmHg/hr, 95% CI: -0.42, 0.06, p = 0.004). Significant heterogeneity between studies was observed for all outcomes (MAP, SBP, DBP: I2 > 85%, p < 0.001). CONCLUSIONS: All BP indices increased progressively with uninterrupted sitting. Over time, prolonged-sitting-induced increases in BP could lead to decreased elasticity in arteries, left-ventricular hypertrophy, or other cardiovascular diseases and symptoms. While considerable heterogeneity was observed (potentially due to variability in age, baseline BP status, and measurement type), results suggest that detrimental increases in BP can be avoided by regularly interrupting sitting.

Validity and success rate of noninvasive mean arterial blood pressure measurements in cf-LVAD patients: A technical review.

The life expectancy of patients with a continuous flow left ventricular assist device (cf-LVAD) is increasing. Adequate determination and regulation of mean arterial pressure (MAP) is important to prevent adverse events. Given the low pulsatility characteristics in these patients, standard blood pressure equipment is inadequate to monitor MAP and not recommended. We provide an overview of currently available noninvasive techniques, using an extensive search strategy in three online databases (Pubmed, Scopus and Google Scholar) to find validation studies using invasive intra-arterial blood pressure measurement as a reference. Mean differences with the reference values smaller than 5 ± 8 mm Hg were considered acceptable. After deduplication, screening, and exclusion of incorrect sources, eleven studies remained with 3139 successful MAP measurements in 386 patients. Four noninvasive techniques, using Doppler, pulse oximetry, finger cuff volume clamp, or slow upper arm cuff deflation, were identified and evaluated for validity and success rate in cf-LVAD patients. Here, a comprehensive technical background of the blood pressure measurement methods is provided in combination with a clinical use comparison. Of the reported noninvasive techniques, slow cuff devices performed most optimally (mean difference 1.3 ± 5.2 mm Hg). Our results are encouraging and indicate that noninvasive blood pressure monitoring options with acceptable validity and success rate are available. Further technical development and validation is warranted for the growing population of patients on long-term cf-LVAD support.

The Use of Non-Invasive Continuous Blood Pressure Measuring (ClearSight®) during Central Neuraxial Anaesthesia for Caesarean Section—A Retrospective Validation Study

: BackgroundThe close monitoring of blood pressure during a caesarean section performed under central neuraxial anaesthesia should be the standard of safe anaesthesia. As classical oscillometric and invasive blood pressure measuring have intrinsic disadvantages, we investigated a novel, non-invasive technique for continuous blood pressure measuring. Methods: In this monocentric, retrospective data analysis, the reliability of continuous non-invasive blood pressure measuring using ClearSight® (Edwards Lifesciences Corporation) is validated in 31 women undergoing central neuraxial anaesthesia for caesarean section. In addition, patients and professionals evaluated ClearSight® through questioning. Results: 139 measurements from 11 patients were included in the final analysis. Employing Bland–Altman analyses, we identified a bias of −10.8 mmHg for systolic, of −0.45 mmHg for diastolic and of +0.68 mmHg for mean arterial blood pressure measurements. Pooling all paired measurements resulted in a Pearson correlation coefficient of 0.7 for systolic, of 0.67 for diastolic and of 0.75 for mean arterial blood pressure. Compensating the interindividual differences in linear regressions of the paired measurements provided improved correlation coefficients of 0.73 for systolic, of 0.9 for diastolic and of 0.89 for mean arterial blood pressure measurements. Discussion: Diastolic and mean arterial blood pressure are within an acceptable range of deviation from the reference method, according to the Association for the Advancement of Medical Instrumentation (AAMI) in the patient collective under study. Both patients and professionals prefer ClearSight® to oscillometric blood pressure measurement in regard of comfort and handling.

COMPARISON OF CONTINUOUS MEAN ARTERIAL PRESSURE BY A WEARABLE CUFF-LESS DEVICE AGAINST INTRA-ARTERIAL MEASUREMENTS

Objective: Wearable cuff-less blood pressure (BP) devices may overcome cuff limitations and offer continuous non-invasive BP monitoring. However, their accuracy in different clinical settings is not yet clarified. This study aimed to evaluate the accuracy of mean arterial pressure (MAP) measurements from a novel continuous cuff-less chest belt against intra-arterial measurements. Design and method: Patients in an intensive care unit with an indication of intra-arterial BP monitoring were included. Reference BP was measured with a radial artery catheter connected to a pressure transducer. Cuff-less measurements were obtained continuously with a chest belt, of which a model for BP estimation was trained on a non-intensive care unit population and consisted of a one-channel electrocardiogram, a photoplethysmography sensor and a tri-axis accelerometer. The data collection was monitored by an investigator to reliably exclude periods where the transducer was not properly levelled. Estimated MAP from the chest-belt was calibrated initially with intra-arterial MAP. In cases where the pressure transducer had to be repositioned, re-calibration was performed due to variability of the repositioned transducer levels. Pairwise comparisons of reference and cuff-less MAP were performed in 15-second epochs. Results: Preliminary data from 9 subjects were analysed. The subjects had a median (interquartile range) age of 64 (58–73) years, median BMI was 28.6 (25.4–32.7) kg/m2and 77.7% were males. A total of 21.5 h of data were analysed with an average of 2.39 ± 1.05 h per subject. The mean difference of estimated versus reference MAP was 3.9 ± 4.2 mmHg. The Bland-Altman bias was 2.06 mmHg with limits of agreement from -9.7 mmHg to 14 mmHg. The Figure displays typical data for one subject (A) and the Bland Altman plot for all subjects (B). Conclusions: After initial calibration with a reference measurement, the cuff-less chest belt estimated changes in mean arterial pressure in close agreement with reference intra-arterial measurements. This study illustrates the potential of a wearable cuff-less device for estimating mean arterial pressure continuously and non-invasively in ospitalised patients.

Unilateral Vagotomy Blunts Cardiorespiratory Responses to Vagal Afferent Stimulation and Nucleus Tractus Solitarii (NTS) Glutamate Microinjection

The nTS of the brainstem is the initial integration site of sensory information from the cardiorespiratory system, including afferents from the vagus nerve carrying input from the heart and lungs. The nTS is an important site of neuroplasticity, which depends on factors including neuronal and astrocytic activity, with the latter regulating glutamate (Glu) signaling. We have shown that unilateral transection of the vagus nerve to decrease afferent input results in morphologic changes in nTS glia. Vagal nerve transection also decreases nTS synaptic transmission studied in vitro. The influence of vagotomy on in vivo cardiorespiratory function via afferent‐driven Glu signaling is unknown. We hypothesized that chronic vagotomy blunts cardiorespiratory responses to vagal afferent stimulation via decreased Glu signaling. Male Sprague‐Dawley rats (6‐wk, N=19) were randomly assigned to vagotomy or sham groups. Right cervical vagus nerve transection caudal to the nodose ganglion or sham surgery was performed. One week after surgery, rats were anesthetized, ventilated, and instrumented to measure mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA, respectively). Intact vagus nerves were transected acutely to prevent efferent stimulation. Left and right vagus nerves were stimulated (20 sec, 0.2mA, 2‐10Hz, 0.5ms pulse width) and responses recorded for 3 minutes. Chronic vagotomy had no effect on baseline cardiorespiratory parameters compared to shams. Vagal nerve stimulation on either side increased MAP, HR, and SSNA and decreased PhrNA in all groups. There were no consistent group differences in MAP, HR, and SSNA responses. However, chronic vagotomy blunted the stimulation‐induced decrease in PhrNA frequency and amplitude and decreased apnea duration on the ipsilateral side compared to contralateral stimulation and to shams. To evaluate the mechanism of altered respiratory responses, Glu was nanoinjected (30nL, 1‐10mM) into the left and right nTS of chronic vagotomy and sham rats. Glu decreased MAP, HR, SSNA, and PhrNA in all groups and on both sides. Chronic vagotomy had minimal effects on MAP and SSNA responses, but blunted the decrease in HR and PhrNA frequency and amplitude during ipsilateral Glu injection compared to contralateral. The blunted responses to vagal afferent stimulation and nTS glutamate suggest that chronic vagotomy alters Glu signaling in part via postsynaptic mechanisms. Additional experiments are needed to determine the mechanisms (including the role of astrocytes) of altered nTS Glu signaling to changes in afferent input in cardiorespiratory health and disease.

OVLT Lesion attenuates hypertension and polydipsia in 2‐kidney, 1‐clip hypertensive Rats

Hypertension (HTN) is a multifaceted condition that affects one‐third of the population of western countries. It is well established that renal ischemia results in secondary renovascular HTN. Experimental renovascular HTN is induced in rats by creating stenosis of the left renal artery, thereby decreasing perfusion pressure (2K1C‐HTN), leading to increased renin‐angiotensin system activity which may act centrally to increase arterial pressure, sympathetic nerve activity, and thirst. The organum vasculosum of the lamina terminalis (OVLT) is a circumventricular organ which is responsive to blood borne substances such as angiotensin II and has been implicated in the regulation of arterial pressure, sympathetic activity, and thirst. Previous studies have shown that OVLT lesion attenuates development of the DOCA‐model of hypertension, but does not modify the water intake (Collister et al., 2018). In the present study we tested the hypothesis that the OVLT is required for the development of 2K1C‐HTN as polydipsia is observed in this model. Male Sprague‐Dawley rats (n=3‐5/group) were randomly selected to receive either electrolytic lesion of the OVLT (OVLTx) or sham operation. After one week, they were instrumented with telemeters to measure mean arterial pressure (MAP). Two weeks after OVLTx, the left renal artery was stenosed by application of a silver clip. MAP was measured continuously for 6 weeks and, once a week, rats were housed in metabolic cages for 24 hours to measure water intake and urine volume. At the end of the protocol, MAP was significantly (p&lt;0.001) lower in OVLTx‐2K1C (134±8 mmHg) compared to sham lesion‐2K1C (163±6 mmHg) rats. In addition, water intake was significantly (p&lt;0.001) lower in OVLTx‐2K1C (42±2 ml/day) compared to sham lesion‐2K1C (73±2 ml/day) rats. Similarly, urinary volume excretion was reduced in OVLTx‐2K1C (25±2 ml/day) compared to sham lesion‐2K1C (52±5 ml/day) rats. We conclude that the integrity of OVLT is required for the development of 2K1C hypertension as well the polydipsia observed following renal artery stenosis.

Renal Afferent Nerves Regulate Salt Appetite in DOCA Hypertensive Rats

Approximately 90% of hypertension is essential, driven by a mix of environmental and genetic factors. One major environmental factor is dietary salt, with 50% of essential hypertension thought to be salt sensitive. The average American consumes 3,400 mg of sodium a day, 1000 mg more than the American Heart Association’s recommended daily allowance. Moreover, the World Health Organization estimates that reducing salt intake to the recommended level could prevent 2.5 million deaths per year globally. Therefore, an improved understanding of the mechanisms regulating the consumption of sodium may provide a novel therapeutic target for the treatment of hypertension. In the current study, we examined whether renal afferent nerves play a role in the control of sodium intake. To test this hypothesis, we examined the effect of afferent renal denervation (ADNX) on sodium intake in DOCA hypertensive rats, a model in which sodium appetite has been shown to be elevated.Male Sprague Dawley rats were surgically prepared at 8‐10 weeks. All rats were implanted with radio‐telemetry catheters in the femoral artery for the measurement of mean arterial pressure (MAP). DOCA was administered using a subcutaneous silicon pellet (100 mg). In half of the DOCA rats, ADNX was performed using the peri‐axonal application of capsaicin (33 mM). In a separate group of Sham rats, a drug‐free silicon pellet was implanted, and the renal nerves were left intact. For ~7‐days before surgery, and throughout the study, all rats were offered two drinking bottles, one containing water and the other 1.8% NaCl. Bottle position was alternated every 24 hours to prevent side preference. 24‐hours after surgery we began daily measurements of fluid intake and MAP. These measurements continued for 3‐weeks.DOCA rats had a significantly higher saline intake than the Sham rats. After 3‐weeks saline intake was 24.7 ± 4 ml/24hr in the DOCA rats (n=17) compared to 13.1 ± 2.3 ml/24hr in the Sham rats (n=13). ADNX caused a significant reduction in saline intake in DOCA rats. Saline intake was significantly lower in the ADNX rats than the DOCA rats from day‐3 onwards (DOCA: 21.7 ± 2.5 ml/24hr vs ADNX: 12.7 ± 1.2 ml/24hr). Notably, after 3‐weeks saline intake in ADNX rats was comparable to that of the Sham rats at 10.8 ± 1.8 ml/24hr (n=18). Water intake was also significantly higher in the DOCA rats than the Sham rats throughout the study. After 3‐weeks water intake averaged 42.0 ± 2.5 ml/24hr compared to 29.1 ± 1.6 ml/24hr in the Sham rats. In contrast to the effects on saline intake, ADNX had no significant effect on water intake, which averaged 39.8 ± 2.1 ml/24hr after 3‐weeks. Indeed, water intake was only significantly different between the ADNX and DOCA rats on 4 of the 21‐days. Interestingly, in this two‐bottle model of DOCA hypertension, ADNX did not have a significant effect on MAP, which after 3‐weeks averaged 143 ± 5 mmHg in the DOCA vs. 136 ± 6 mmHg in the ADNX rats.These studies suggest that afferent renal nerves increase sodium appetite in DOCA rats. Disruption of afferent signals from the kidney caused a significant and sustained reduction in sodium intake, with minimal effects on water intake. These results suggest that reduction of sodium intake may be an additional benefit of renal denervation as a treatment for salt‐dependent hypertension.

Bile Duct Ligation Differently Effects Plasma Osmolality but not Blood Pressure in Male vs Female Rats

Dilutional hyponatremia is known to increase morbidity in patients with advanced liver disease due to the inappropriate release of arginine vasopressin (AVP). Our previous studies show that bile duct ligation (BDL), an animal model of liver disease, increase circulating copeptin in male rats but a decrease in osmolality as compared to the shams. Female BDL rats did not demonstrate the same increase in circulating copeptin or decrease in plasma osmolality as compared to sham females. In this study, we tested if male and female BDL rats showed differences in their blood pressure responses to BDL. Previous studies indicate that male BDL rats become hypotensive while females have not been tested. Adult male and female Sprague Dawley rats had either BDL or sham ligation surgery and were implanted with radio telemetry transmitters for measuring Mean arterial pressure (MAP) and heart rates (HR). Rats were housed in a commercial metabolic cage for one week prior to euthanasian to measure water intake and urine output. No change was seen in daily water intake between the male BDL and sham groups, however the female BDL animals had a significant increase in their daily water intake (p &lt; 0.05, n =6) when compared to the shams. Despite the increase in water intake seen only in BDL females, both the male and female BDL groups saw a large increase in daily urine output (p &lt; 0.001, n = 4‐9) compared to the shams. Analysis of variance showed that there was a main effect of treatment (F(3, 20)= 6.7, P &lt; 0.05) that was due to the MAP of both male and female BDL groups being significantly lower than female shams (P &lt; 0.05). Heart rate was not different among either sexes or treatment groups. Liver weight to body weight ratio was significantly increased in both male and female BDL rats. These results show that both male and female BDL rats became hypotensive when compared to their shams, however the differences in development of hyponatremia among the male and female rats are not due to difference in blood pressure changes associated with BDL.

Effects of Fumarate on Blood Pressure and Renal Hemodynamics in Normotensive Rats: Possible Contribution of Sodium Potassium Co‐transporter (NKCC)

The tricarboxylic acid cycle product, fumarate, and its related products, have been implicated in the etiology of genetic and non‐genetic models of hypertension. Fumarate showed a mechanistic link to nitric oxide (NO) production and thus impacted blood pressure and renal hemodynamics in both models. This study evaluated the possibility of a role of fumarate in regulation of blood pressure and renal hemodynamics in normotensive rats and elucidate possible mechanisms involved. Animals were anaesthetized with Thiobutabarbital (100 mg/kg, ip). The carotid artery was cannulated for mean arterial blood pressure (MABP) measurement and the left kidney was exposed to measure cortical blood flow (CBF) and medullary blood flow (MBF). Blood and urine were collected to determine glomerular filtration rate (GFR), urine volume (Uv) and sodium excretion (UNaV). The fumarase inhibitor, pyromellitic acid (PMA) (0.1 mg/kg/h), or fumarate (0.1 mg/kg/h) were infused in these animals. To determine renal sodium excretory mechanisms involved with fumarate, fumarate (1 mg/kg, po) was administered to normotensive rats treated with hydrochlorothiazide (HCTZ) (10 mg/kg, po) or furosemide (10 mg/kg, po), urine was collected hourly for five (5) hours and assayed for sodium. Fumarate elicited a hypotensive effect, with peak effect at the 45th minute (126 ± 6.2 vs 93 ±2.6 mmHg, p&lt;0.05). Similarly, inhibition of fumarase caused a time‐dependent decrease in MABP (p&lt;0.05). There was a consistent drop in CBF in fumarate‐infused rats and although PMA caused an initial rise in CBF at 15 mins, there was a 10‐fold increase in CBF at 60 min when compared to fumarate‐infused rats (p&lt;0.05). MBF also decreased in a time‐dependent fashion in rats infused with fumarate. Consistent with the drop in MABP and CBF, GFR reduced (0.89 ± 0.26 vs 0.39 ± 0.11 mL/min, p&lt;0.05) at 30 mins before to returning to baseline levels at 60 mins in fumarate‐infused rats. Uv was unchanged in rats infused with fumarate but there was a 1‐fold reduction in UNaV at 30 mins (p&lt;0.05). Also, PMA, tended to increase UNaV at 30 mins, compared to baseline. However, there was an exacerbation in UNaV in PMA‐infused rats (24.2 ± 3.8 µmol/L) compared to fumarate‐infused rats at 30 mins (4.56 ±1.4 µmol/L, p&lt;0.05). Fumarate increased UNaV compared to control (p&lt;0.05), however, there was no significant difference in UNaV between furosemide‐treated and furosemide‐treated fumarate rats. These data indicate that fumarate and its products elicited vasodilatory effects that reduced blood pressure and exerted vascular and tubular effects on renal hemodynamics. Also, the tubular effects, possibly involves inhibition of sodium potassium co‐transporter (NKCC).