Mean Arterial Pressure Research Articles

Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China

IntroductionPatients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus....

Living-donor lobar lung transplantation for pulmonary Langerhans cell histiocytosis complicated by extensive thrombi in central pulmonary arteries

BackgroundPulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterized by the proliferation of Langerhans cells along the small airways, which causes nodular and cystic changes in the lung parenchyma. Lung transplantation can be a life-saving option for patients with severe respiratory failure or pulmonary hypertension. Herein, we present a case of successful lung transplantation in a patient with PLCH who developed unusually large thrombi in the central pulmonary artery.Case presentationA 47-year-old woman with 16-year history of PLCH with rapidly developing respiratory failure was admitted to our hospital for the evaluation of a lung transplant. Enhanced computed tomography revealed large thrombi in dilated central pulmonary arteries. Right heart catheterization revealed severe pulmonary hypertension, with a mean pulmonary artery pressure of 48 mmHg. The thrombi shrank markedly after 3 months of anticoagulation therapy. However, the respiratory status of the patient did not improve. We performed bilateral living-donor lobar lung transplantation with thrombectomy under extracorporeal membrane oxygenation for the remaining thrombi in the main pulmonary arteries. The dilated main pulmonary arteries of the recipient required direct plication for size mismatch. The patient survived in good condition for more than 2 years with no recurrence of thrombosis.ConclusionPreoperative anticoagulation therapy for massive thrombi in the pulmonary arteries was effective and led to safe lung transplantation.

Influence of sustained mild dehydration on thermoregulatory and cognitive functions during prolonged moderate exercise.

The current study investigated whether sustained mild dehydration affects thermoregulatory function and cognitive performance during prolonged exercise. Twelve young adults performed a test consisting of three sets of 20-min exercise with 2-min intervals under euhydrated (control, CON) and mildly dehydrated conditions (MDEH) at an ambient temperature of 30°C and 60% relative humidity. MDEH was established by restricting water intake for 24h, resulting in urine specific gravity of ≥ 1.020. Heart rate (HR), mean arterial blood pressure (MAP), skin blood flow (SkBF), sweat rate (SR) on the chest and forearm, and ear canal and mean skin surface temperatures (Tear and mean Tskin, respectively) were continuously recorded. For each exercise set, thermal and humid sensations and thermal discomfort were assessed using visual analog scales (VAS), and the rating of perceived exertion (RPE) was estimated. Cognitive performance on the Go/No-Go (easy) and incongruent Stroop (difficult) tasks was assessed before and after the test. No differences were observed in HR, MAP, SkBF, SR, Tear, and mean Tskin between the CON and MDEH. Thermal and humidity sensations, thermal discomfort, and RPE were higher in MDEH than in CON. Moreover, response time to the Stroop task was prolonged in MDEH. These findings suggest that sustained mild dehydration does not affect autonomic thermoregulation during exercise. Augmented thermal perception and perceived exertion, which are necessary for behavioral thermoregulation, were noted; however, cognitive function may be attenuated under MDEH.

Association between early pregnancy maternal blood pressure and risk of congenital heart disease in offspring

Objective: To analyze the association between maternal blood pressure and congenital heart disease (CHD) in offspring. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal and Child Healthcare Hospital and Chengdu Women's and Children's Central Hospital were enrolled in this study. The baseline and follow-up information were collected using an electronic data collection system. Stepwise logistic regression model was used to analyze the association between maternal blood pressure including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure difference (PP) in the first trimester of pregnancy and the risk of CHD in the offspring. A restrictive cubic spline curve was used to draw the dose-response curve between maternal blood pressure and CHD. Results: A total of 55 552 participants were included in this study. Of them, 31 038, 15 375 and 9 139 pregnant women were enrolled in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal & Child Healthcare Hospital and Chendu Women's and Children's Central Hospital, respecitively. The age of pregnant women was (31.3±4.0) and the incidence of CHD in the offspring was 0.78% (435/55 552). Multivariable logistic regression model analysis showed that the increase of SBP (OR=1.01, 95%CI: 1.00-1.02), DBP (OR=1.01, 95%CI: 1.00-1.03) and MAP (OR=1.02, 95%CI: 1.00-1.03) in the first trimester were significantly associated with the risk of CHD in the offspring. The restrictive cubic spline analysis showed a positive linear association of SBP (Ptotal<0.001; Pnon-liear=0.315), DBP (Ptotal<0.001; Pnon-liear=0.928) and MAP (Ptotal<0.001; Pnon-liear=0.929) with the risk of CHD in the offspring. Conclusion: Maternal SBP, DBP and MAP in the first trimester of pregnancy were positively associated with the risk of CHD in the offspring.

Renal and patient outcomes of emergency hemodialysis in elderly individuals: a retrospective cohort study.

The aging population, commonly defined as individuals aged 65 and above, faces an increased risk of kidney-related diseases. This study investigates emergency dialysis in the elderly population, focusing on indications, clinical and laboratory findings, renal status, and mortality rates. The data of 442 elderly patients (≥ 65years old) who underwent emergency dialysis at a tertiary university hospital were retrospectively examined. Demographics, comorbidities, emergency dialysis indications, clinical presentation, method, complications, pre/post-dialysis status, and follow-up were assessed. 74.9% of the patients had a history of chronic kidney disease (CKD). Emergency dialysis was mainly initiated due to hypervolemia (43.7%) and uremic symptoms (29.2%). Hypotension was the most common dialysis-related complication (34.4%). The mortality rate was 34.6%; among the survivors, 15.2% achieved complete renal recovery, while 32.5% and 52.3% developed dialysis-independent and -dependent CKD, respectively. In multivariate analysis, blood urea, serum sodium, mean arterial pressure, dyspnea, tachypnea, and tachycardia on admission were found to be associated with mortality. Our study provides insights into emergency dialysis challenges in the elderly population, emphasizing the need for personalized interventions and further research to improve care and outcomes in this growing demographic.

Pd/Pa fluctuation with continuous ATP administration indicates inaccurate FFR measurement caused by insufficient hyperemia.

Continuous intravenous adenosine triphosphate (ATP) administration is the standard method for inducing maximal hyperemia in fractional flow reserve (FFR) measurements. Several cases have demonstrated fluctuations in the ratio of mean distal coronary pressure to mean arterial pressure (Pd/Pa) value during ATP infusion, which raised our suspicions of FFR value inaccuracy. This study aimed to investigate our hypothesis that Pd/Pa fluctuations may indicate inaccurate FFR measurements caused by insufficient hyperemia. We examined 57 consecutive patients with angiographically intermediate coronary lesions who underwent fractional flow reverse (FFR) measurements in our hospital between November 2016 and September 2018. Pd/Pa was measured after continuous ATP administration (150μg/kg/min) via a peripheral forearm vein for 5min (FFRA); and we analyzed the FFR value variation in the final 20s of the 5min, defining 'Fluctuation' as variation range > 0.03. Then, 2mg of nicorandil was administered into the coronary artery during continued ATP infusion, and the Pd/Pa was remeasured (FFRA+N). Fluctuations were observed in 23 of 57 patients. The cases demonstrating discrepancies of > 0.05 between FFRA and FFRA+N were observed more frequently in the fluctuation group than in the non-fluctuation group (12/23 vs. 1/34; p < 0.0001). The discrepancy between FFRA and FFRA+N values was smaller in the non-fluctuation group (mean difference ± SD; -0.00026 ± 0.04636 vs. 0.02608 ± 0.1316). Pd/Pa fluctuation with continuous ATP administration could indicate inaccurate FFR measurements caused by incomplete hyperemia. Additional vasodilator administration may achieve further hyperemia when Pd/Pa fluctuations are observed.

Risk factors and prognosis of postoperative spinal cord injury in type A aortic dissection.

To investigate the risk factors and prognosis of spinal cord injury (SCI) after surgical procedure in type A aortic dissection (AAD). Between January 2013 and December 2021, a total of 1647 patients with AAD underwent surgical procedure. Postoperative SCI occurred in 58 patients, including 24 patients with paraplegia and 34 patients with paraparesis. Factors associated with SCI was identified through comparison between patients with and without SCI. The mean age was 48.8 ± 10.8 years for patients with SCI and 50.1 ± 12.1 years for those without SCI (P = 0.43), with a comparable gender distribution. Median numbers of intercostal and lumbar arteries with involvement were significantly higher in the SCI group (both P < 0.001). The highest (P = 0.033) and lowest (P = 0.001) level of intraoperative mean arterial pressure (MAP) were significantly lower in the SCI group. Multivariable analysis revealed number of segmental arteries involved (odds ratio [OR]=1.14, 95% CI 1.08-1.20, P = 0.000) and duration of hypothermic circulatory arrest (HCA) (OR = 1.04, 95% CI 1.01-1.08, P = 0.042) were positively associated with the occurrence of SCI. Conversely, the lowest level of MAP was negatively associated with SCI (OR = 0.98, 95% CI 0.96-0.99, P = 0.031). During the long-term follow-up, 14 patients with paraplegia needed the wheel chair, while only one patient with paraparesis needed one (P < 0.001). The risk of postoperative SCI increases when AAD patients experience segmental arteries involved, longer HCA duration, and decreased intraoperative MAP during operation.

Effects of sodium-glucose transporter-2 inhibition on systemic hemodynamics, renal function, and intra-renal oxygenation in sepsis-associated acute kidney injury.

People with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI. Sixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8). Empagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9mmHg in the empagliflozin group compared with 40.6 ± 8.2mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5mmHg in the empagliflozin compared with 25.7 ± 16.3mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes. In a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.

Mode of cell death in the penile cavernous tissue of type 1 diabetes mellitus rats.

Diabetes mellitus commonly causes endothelial cell and smooth muscle cell death in penile cavernous tissue. The study sought to study the mode of cell death in the penile cavernous tissue in type 1 diabetic rats. A total of 36 Sprague Dawley rats 10 weeks of age were randomly divided into 2 groups: a normoglycemic group and type 1 diabetic group (intraperitoneal injection of Streptozotocin (STZ), 60mg/kg). We randomly selected 6 rats from each group for tests at the end of 11, 14, and 18weeks of age, respectively. All rats were able to eat and drink freely. The ratio of maximum intracavernous pressure to mean arterial pressure, concentration of serum testosterone, level of nitric oxide in the penile cavernosum, and expression of active caspase-1 (pyroptosis) and active caspase-3 (apoptosis) were determined. At the end of weeks 4 and 8 of type 1 diabetes, the proportions of endothelial cells and smooth muscle cells undergoing apoptosis and pyroptosis in penile cavernous tissue are different. The ratio of maximum intracavernous pressure to mean arterial pressure and nitric oxide levels were significantly lower in the 4- and 8-week diabetic groups than in the normoglycemic group (P < .01). Penile endothelial cell pyroptosis (5.67 ± 0.81%), smooth muscle cell apoptosis (23.72 ± 0.48%), total cell pyroptosis (9.67 ± 0.73%), and total apoptosis (10.52 ± 1.45%) were significantly greater in the 4-week diabetic group than in the normoglycemic group (P < .01). The proportion of endothelial cell pyroptosis (24.4 ± 3.69%), endothelial cell apoptosis (22.13 ± 2.43%), total cell pyroptosis (14.75 ± 0.93%), and total apoptosis (14.82 ± 1.08%) in the penile tissues of the 8-week diabetic group were significantly greater than those in the normoglycemic group (P < .01).The 8-week survival proportions of diabetic endothelial cells (38.86 ± 8.85%) and smooth muscle cells (44.46 ± 2.94%) was significantly lower than the 4-week survival proportions of endothelial cells (93.17 ± 8.07%) and smooth muscle cells (75.12 ± 4.76%) (P < .05). Inhibition of cell death by different methods at different stages may be the key to the treatment of type 1 diabetes-induced erectile dysfunction. The effect of type 1 diabetes on other types of cell death in penile cavernous tissue needs further study. The mode of death of endothelial cells in the cavernous tissue of the penis in the early stage in diabetic rats is dominated by pyroptosis, and the death of smooth muscle cells is dominated by apoptosis. Endothelial cell and smooth muscle cell death are not consistent at different stages of diabetes progression.

New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Veno-Arterial Extracorporeal Membrane Oxygenation in the Rat

Despite significant efforts toward improving therapy for septic shock, mortality remains high. Applying veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) in this context remains controversial. Since the cannulation of the femoral artery for V-A ECMO return leads to lower body hyperoxia, this study investigated the impact of V-A ECMO therapy on the intestinal and hepatic microcirculation during septic shock in a rodent model. Thirty male Lewis rats were randomly assigned to receive V-A ECMO therapy with low (60 mL/kg/min) or high (90 mL/kg/min) blood flow or a sham procedure. Hemodynamic data were collected through a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by intravenous administration of lipopolysaccharide (1 mg/kg). The rats received lung-protective ventilation during V-A ECMO therapy. The hepatic and intestinal microcirculation was measured by micro-lightguide spectrophotometry after median laparotomy for two hours. Systemic and pulmonary inflammation was detected via enzyme-linked immunosorbent assays (ELISA) of the plasma and bronchoalveolar lavage (BAL), respectively, measuring tumor necrosis factor-alpha (TNF-α), interleukins 6 (IL-6) and 10 (IL-10), and C-X-C motif ligands 2 (CXCL2) and 5 (CXCL5). Oxygen saturation and relative hemoglobin concentration were reduced in the hepatic and intestinal microcirculation during V-A ECMO therapy, independent of the blood flow rate. Further, rats treated with V-A ECMO therapy also presented elevated systolic, diastolic, and mean arterial blood pressure and increased stroke volume, cardiac output, and left ventricular end-diastolic volume. However, left ventricular end-diastolic pressure was only elevated during high-flow V-A ECMO therapy. Blood gas analysis revealed a dilutional anemia during V-A ECMO therapy. ELISA analysis showed an elevated plasma CXCL2 concentration only during high-flow V-A ECMO therapy and elevated BAL CXCL2 and CXCL5 concentrations only during low-flow V-A ECMO therapy. Rats undergoing V-A ECMO therapy exhibited impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Increased pulmonary inflammation was detected only during low-flow V-A ECMO therapy in septic shock.

Effects of Remimazolam versus Sevoflurane on Hemodynamics in Patients Undergoing Coil Embolization of Cerebral Aneurysm: A Prospective Randomized Controlled Trial

Background: Cerebral aneurysm coil embolization is often performed under general anesthesia to prevent patient movement and sudden high blood pressure. However, the optimal anesthetic agent remains uncertain. This study aimed to determine whether maintaining anesthesia with remimazolam in patients undergoing coil embolization could avoid hypotension or hypertension compared to sevoflurane. Methods: Thirty-three adult patients participated in this single-blinded, randomized controlled trial. Patients in Group R were induced and maintained with remimazolam, whereas those in Group S received propofol and sevoflurane. Results: The use of remimazolam significantly reduced the incidence of intraoperative hypotension events (33.3% vs. 80.0%; p = 0.010) but did not change the incidence of hypertension events (66.7% vs. 73.3%; p = 0.690). Patients in Group R maintained a significantly higher range of maximal (100.2 ± 16.6 vs. 88.1 ± 13.5 mmHg; p = 0.037) and minimal (69.4 ± 6.6 vs. 63.4 ± 4.8 mmHg; p = 0.008) mean arterial blood pressure than those in Group S during the intervention. Conclusions: This is the first study to demonstrate the feasibility of maintaining general anesthesia with remimazolam in patients undergoing cerebral aneurysm coil embolization. The findings suggest that remimazolam may maintains better hemodynamic stability, reducing the incidence of hypotensive events without compromising patient safety.

Effect of zamicastat on blood pressure and heart rate response to cold pressor test: A double-blind, randomized, placebo-controlled study in healthy subjects.

Dopamine beta-hydroxylase (DβH) inhibitors, like zamicastat, hold promise for treating pulmonary arterial hypertension. This study aimed to validate the mechanism of action of zamicastat by studying its effect on the overdrive of the sympathetic nervous system (SNS). A single-centre, prospective, double-blind, randomized, placebo-controlled, crossover study evaluated the effect of 400 mg zamicastat in 22 healthy male subjects. Cold pressor test (CPT) was performed at screening and each treatment period on Days -1 and 10. Plasma and 24 h-urine levels of dopamine (DA), epinephrine (EPI) and norepinephrine (NE), and plasma DβH activity, were measured. Compared to placebo, zamicastat showed a - 4.62 mmHg decrease in systolic blood pressure during the cold stimulus vs. rest phases on Day 10 of CPT (P = .020). Zamicastat decreased mean arterial pressure response to cold stimulus during CPT (-2.62 mmHg; P = .025). At Day 10, zamicastat significantly increased plasma DA, before CPT (12.63 ng/L; P = .040) and after CPT (19.22 ng/L; P = .001) as well as the estimated plasma EPI change from baseline after CPT (P = .040). Inhibition of plasma DβH activity ranged from 19.8% to 25.0%. At Day 10, significant reductions in 24-h urinary excretion of EPI (P = .002) and NE (P = .001) were observed. Zamicastat Cτ geometric mean ± GSD ranged from 45.86 ± 1.46 ng/mL on Day 3 to 58.64 ± 1.52 ng/mL on Day 10, with moderate inter-individual variability (CV: 32.6%-36.6%). Steady state was already achieved on Day 6. Our results demonstrated the effect of zamicastat on the overdrive sympathetic response to cold stimulus, confirming its potential as SNS modulator.

Supervised Machine Learning to Examine Factors Associated with Respiratory Sinus Arrhythmias and Ectopic Heart Beats in Adults: A Pilot Study

Background: There are many types of arrhythmias which may threaten health that are well-known or opaque. The purpose of this pilot study was to examine how different cardiac health risk factors rank together in association with arrhythmias in young, middle-aged, and older adults. Methods: The analytic sample included 101 adults aged 50.6 ± 22.6 years. Several prominent heart-health-related risk factors were self-reported. Mean arterial pressure and body mass index were collected using standard procedures. Hydraulic handgrip dynamometry measured strength capacity. A 6 min single-lead electrocardiogram evaluated arrhythmias. Respiratory sinus arrhythmias (RSAs) and ectopic heart beats were observed and specified for analyses. Classification and Regression Tree analyses were employed. Results: A mean arterial pressure ≥ 104 mmHg was the first level predictor for ectopic beats, while age ≥ 41 years was the first level predictor for RSAs. Age, heart rate, stress and anxiety, and physical activity emerged as important variables for ectopic beats (p &lt; 0.05), whereas age, sodium, heart rate, and gender were important for RSAs (p &lt; 0.05). Conclusions: RSAs and ectopic arrhythmias may have unique modifiable and non-modifiable factors that may help in understanding their etiology for prevention and treatment as appropriate across the lifespan.

Degree of PEGylatation of Lumbricus terrestris Hemoglobin Improves Microcirculatory Blood Flow but Increases the Rate of Auto-Oxidation.

The demand for red blood cells (RBCs) is on the rise due to the increasing diagnosis of chronic diseases such as sickle cell anemia, malaria, and thalassemia. Despite many commercial attempts, there are no U.S. FDA-approved artificial RBCs for use in humans. Existing RBC substitutes have employed various strategies to transport oxygen, extend the circulation time, and reduce organ toxicity, but none have replicated the natural protective mechanisms of RBCs, which prevent hemoglobin (Hb) dimerization and heme iron oxidation. Lumbricus terrestris (earthworm) erythrocruorin (LtEc) is a naturally occurring extracellular hemoglobin (Hb) with promising attributes: large molecular diameter (30 nm), high molecular weight (3.6 MDa), low auto-oxidation rate, and limited nitric oxide-scavenging properties. These characteristics make LtEc an ideal candidate as an RBC substitute. However, LtEc has a significant drawback, its short circulatory half-life. To address this issue, we explored thiol-mediated surface PEGylation of LtEc (PEG-LtEc) at varying polyethylene glycol (PEG) surface coverages. Increasing PEG surface coverage beyond 40% destabilizes LtEc into smaller subunits that are 1/12th the size of LtEc. Therefore, we evaluated two PEG surface coverage options: PEG-LtEc-0.2 (20% PEGylation) and PEG-LtEc-1.0 (100% PEGylation). We conducted experiments using golden Syrian hamsters with dorsal window chambers and catheters to assess the efficacy of these solutions. We measured microvascular parameters, organ function, cerebral blood flow, circulation time, mean arterial pressure, heart rate, and blood gases and performed histology to screen for toxicity. Our findings indicate that both PEG-LtEc molecules offer significant benefits in restoring microvascular parameters, organ function, cerebral blood flow, and circulation time compared to LtEc alone. Notably, PEG-LtEc-1.0 showed superior microvascular perfusion, although it exhibited a higher rate of auto-oxidation compared to PEG-LtEc-0.2. These results underscore the advantages of PEGylation in terms of tissue perfusion and organ health while highlighting its limitations.

Risk prediction for preeclampsia in CKD patients: development of a model in a retrospective cohort.

Chronic kidney disease (CKD) mayaffect women of childbearing age and maylead to substantial maternal and foetal morbidity and mortalityin pregnancy. There is a lack of prediction models for preeclampsia and adverse pregnancy outcomes in pregnant women with CKD. This study aimed to create a prediction nomogram for these issues. This retrospective cohort study included clinical data from 627 women with CKD and their 627 pregnancies at Peking University First Hospital between January 1, 2009, and December 31, 2022. Multivariate logistic regression analysis was conducted to identify independent prognostic factors and develop a nomogram for predicting the occurrence of preeclampsia. The identified risk factors were utilised to construct the nomogram, which was subsequentlyinternally validated using receiver operating characteristic (ROC) analysis and calibration curve assessment. According to our multivariate analysis, age, blood urea nitrogen (BUN), serum creatinine (Scr), mean arterial pressure (MAP), 24-h proteinuria, and CKD stage were identified as predictors of preeclampsia. Additionally, Scr, MAP, BUN, and 24-h proteinuria were found to be predictors of adverse pregnancy outcomes. The nomogram for predicting preeclampsia had an area under the ROC curve of 0.910, while the nomogram for predicting adverse pregnancy outcomes had an area under the ROC curve of 0.906. Both models demonstrated excellent discriminatory ability. A nomogram based on 24-h proteinuria, serum creatinine, serum urea and age, and MAP allows predicting the occurrence of preeclampsia and other adversepregnancy-related outcomes in CKD patients.

A prediction model for stillbirth based on first trimester pre-eclampsia combined screening.

To evaluate the accuracy of combined models of maternal biophysical factors, ultrasound, and biochemical markers for predicting stillbirths. A retrospective cohort study of pregnant women undergoing first-trimester pre-eclampsia screening at 11-13 gestational weeks was conducted. Maternal characteristics and history, mean arterial pressure (MAP) measurement, uterine artery pulsatility index (UtA-PI) ultrasound, maternal ophthalmic peak ratio Doppler, and placental growth factor (PlGF) serum were collected during the visit. Stillbirth was classified as placental dysfunction-related when it occurred with pre-eclampsia or birth weight <10th percentile. Combined prediction models were developed from significant variables in stillbirths, placental dysfunction-related, and controls. We used the area under the receiver-operating-characteristics curve (AUC), sensitivity, and specificity based on a specific cutoff to evaluate the model's predictive performance by measuring the capacity to distinguish between stillbirths and live births. There were 13 (0.79%) cases of stillbirth in 1643 women included in the analysis. The combination of maternal factors, MAP, UtA-PI, and PlGF, significantly contributed to the prediction of stillbirth. This model was a good predictor for all (including controls) types of stillbirth (AUC 0.879, 95% CI: 0.799-0.959, sensitivity of 99.3%, specificity of 38.5%), and an excellent predictor for placental dysfunction-related stillbirth (AUC 0.984, 95% CI: 0.960-1.000, sensitivity of 98.5, specificity of 85.7). Screening at 11-13 weeks' gestation by combining maternal factors, MAP, UtA-PI, and PlGF, can predict a high proportion of stillbirths. Our model has good accuracy for predicting stillbirths, predominantly placental dysfunction-related stillbirths.

Sympathetic Baroreflex Sensitivity is Enhanced in Postmenopausal Women.

The sympathetic nervous system is critical for regulating blood pressure (BP) via the arterial baroreflex as well as sympathetic transduction in the peripheral vasculature. These mechanisms interact and both may be altered with aging and impacted by menopause. Although age-related decreases in sympathetic transduction have been demonstrated in women, it remains unclear whether sympathetic baroreflex sensitivity (BRS) is impaired in postmenopausal women (POST). We tested the hypothesis that sympathetic BRS would be enhanced in POST compared to premenopausal women (PRE). We examined beat-by-beat BP and muscle sympathetic nerve activity (MSNA) in 19 PRE (22±2 yr, 22±3 kg/m2) and 12 POST (57±5 yr, 24±2 kg/m2) during 10 minutes of rest. Spontaneous sympathetic BRS was quantified as the slope of a linear regression between MSNA burst incidence and diastolic BP. Sympathetic transduction to mean arterial pressure (MAP) for the 10-cardiac cycles following spontaneous MSNA bursts was assessed via signal averaging method. Resting MAP was similar (PRE: 82±8 vs. POST: 85±8 mm Hg, P=0.43), whereas resting MSNA was elevated in POST (PRE: 10±6 vs. POST: 45±16 bursts/100 heartbeats, P<0.0001). Spontaneous sympathetic BRS was enhanced in POST (PRE: -2.0±1.2 vs. POST: -5.2±1.9 bursts/beat/mm Hg, P<0.0005). Sympathetic transduction to MAP was attenuated in POST (Time: P<0.001, Group: P<0.001, Interaction: P<0.01). These data suggest that sympathetic BRS may be enhanced in POST. Consistent with recent hypotheses, enhanced sensitivity of the arterial baroreflex's neural arc may signify a compensatory response to reduced efficiency of the peripheral arterial baroreflex arc (i.e., sympathetic transduction) to preserve BP buffering capacity.

Nicotine exacerbates exertional heat strain in trained men: A randomized, placebo-controlled, double-blind study.

To determine if using nicotine exacerbates exertional heat strain through an increased metabolic heat production (Hprod) or decreased skin blood flow (SkBF), ten nicotine-naïve trained males (37±12 y; VO2peak: 66±10 ml·min-1·kg-1) completed four trials at 20°C and 30°C following overnight transdermal nicotine (7mg·24h-1) and placebo use in a crossover, double-blind design. They cycled for 60 min (55% VO2peak) followed by a time-trial (~75% VO2peak) during which measures of gastro-intestinal (Tgi) and mean weighted skin ( sk) temperatures, SkBF, Hprod, and mean arterial pressure (MAP) were made. The difference in ∆Tgi between nicotine and placebo trials was greater during 30°C (0.4±0.5°C) than 20°C (0.1±0.7°C), with sk higher during nicotine than placebo trials (0.5±0.5°C, p=0.02). SkBF became progressively lower during nicotine than placebo trials (p=0.01) and progressively higher during 30°C than 20°C trials (p<0.01); MAP increased from baseline (p<0.01) and remained elevated in all trials. The difference in Hprod between 30°C and 20°C trials was lower during nicotine than placebo (p=0.01) and became progressively higher during 30°C than 20°C trials with exercise duration (p=0.03). Mean power output during the time-trial was lower during 30°C than 20°C trials (24±25 W, p=0.02), and although no effect of nicotine was observed (p>0.59) two participants (20%) were unable to complete their 30°C nicotine trials as one reached the ethical limit for Tgi (40.0°C) whilst the other withdrew due to "nausea and chills" (Tgi=39.7°C). These results demonstrate that nicotine use increases thermal strain and risk of exertional heat exhaustion by reducing SkBF.

Association of Adiposity, Serum Vitamin D and Dietary Quality with Cardiometabolic Risk in Children aged 6 to 12 years: Findings from SEANUTS II Malaysia

Increased cardiometabolic risk among children is increasingly becoming a concern, with evidence indicating that obesity, diet, and serum 25-hydroxyvitamin D (25(OH)D) are associated with cardiometabolic risk. However, such studies among Malaysian children are scarce. Thus, this study explores the associations between adiposity, dietary quality, and 25(OH)D, with cardiometabolic risk factors among Malaysian children aged 4-12 years. Data of 4879 children (mean age: 8.2±2.3 years old, 53% females) from the South East Asian Nutrition Surveys (SEANUTS II) Malaysia, were analysed. Adiposity (percentage of body fat) was assessed with bioelectrical impedance technique. Dietary quality was assessed using 24-hour dietary recall and calculated as mean adequacy ratio (MAR). Vitamin D was assessed based on serum 25-hydroxyvitamin D (25(OH)D). Measurements of cardiometabolic risk factors included waist circumference, mean arterial pressure, fasting blood glucose, high-density lipoprotein (HDL), triglyceride, and high-sensitivity C-reactive protein, and cardiometabolic risk cluster score (siMS) was calculated. Overall, higher adiposity was positively associated with all cardiometabolic risk factors (WC, ß=0.907; 95%CI=0.865,0.948; MAP, ß=0.225; 95%CI=0.158, 0.292; HDL, ß =-0.011; 95%CI=-0.014, -0.009; Triglyceride, ß=0.012; 95%CI=0.009, 0.016; FBG, ß=0.006; 95%CI=0.002, 0.011) and siMS scores (ß=0.033; 95%CI=0.029, 0.037). Serum 25(OH)D was inversely associated with siMS scores (ß= -0.002; 95%CI= -0.004, -0.000008) and positively associated with HDL (ß=0.002; 95%CI=0.0001, 0.003). Our findings suggest that adiposity is a key determinant of adverse cardiometabolic risk factors in children, while serum 25(OH)D may be associated with overall cardiometabolic health. Interventions to reduce obesity are needed to mitigate the deleterious consequences of cardiometabolic dysregulation in children.

Dynamics of critical closing pressure explain cerebral autoregulation impairment in acute cerebrovascular disease.

Cerebral autoregulation (CA) is impaired in acute ischemic stroke (AIS) and is associated with worse patient outcomes, but the underlying physiological cause is unclear. This study tests whether depressed CA in AIS can be linked to the dynamic responses of critical closing pressure (CrCP) and resistance area product (RAP). Continuous recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), arterial blood pressure (BP), end-tidal CO2 and electrocardiography allowed dynamic analysis of the instantaneous MCAv-BP relationship to obtain estimates of CrCP and RAP. The dynamic response of CrCP and RAP to a sudden change in mean BP was obtained by transfer function analysis. Comparisons were made between younger controls (≤50 years), older controls (&gt;50 years), and AIS patients. Data from 24 younger controls (36.4 ± 10.9 years, 9 male), 38 older controls (64.7 ± 8.2 years, 20 male), and 20 AIS patients (63.4 ± 13.8 years, 9 male) were included. Dynamic CA was impaired in AIS, with lower autoregulation index (affected hemisphere: 4.0 ± 2.3, unaffected: 4.5 ± 1.8) compared to younger (right: 5.8 ± 1.4, left: 5.8 ± 1.4) and older (right: 4.9 ± 1.6, left: 5.1 ± 1.5) controls. AIS patients also demonstrated an early (0-3 second) peak in CrCP dynamic response, that was not influenced by age. These early transient differences in the CrCP dynamic response are a novel finding in stroke and occur too early to reflect underlying regulatory mechanisms. Instead, these may be caused by structural changes to cerebral vasculature. .