Mean Arterial Pressure Research Articles

Development of a new micellar formulation of carvedilol and curcumin to enhance blood pressure reduction in a spontaneously hypertensive rat model.

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, requiring innovative therapeutic strategies. This project explores a nano-pharmaceutical approach to enhance the efficacy of cardiovascular drugs, focusing on carvedilol and curcumin. These agents, known for their potential cardiovascular benefits, are encapsulated within Soluplus® micelles to form a novel drug delivery system. The novelty of this formulation lies in its ability to significantly improve the solubility of both carvedilol and curcumin, which have traditionally been limited by their hydrophobic nature. By utilizing Soluplus® micelles, we have developed a unique delivery system that optimizes the therapeutic potential of both drugs. The nanomicelles were meticulously characterized for drug loading, size distribution, and morphological features. The carvedilol and curcumin release patterns were investigated, revealing sustained and controlled release profiles. Additionally, the antioxidant capacity of the micellar formulation was evaluated, demonstrating the preservation of curcumin's antioxidative properties. In vivo studies using spontaneously hypertensive male rats explored the pharmacokinetics and hemodynamic effects of the nanomicellar system. These results indicated successful encapsulation of both drugs without altering their plasma profiles. Furthermore, the administration of carvedilol and curcumin micelles exhibited a more significant reduction in mean arterial pressure compared to individual drug administration, suggesting a potential synergistic effect. In conclusion, this nano-pharmaceutical approach offers a promising avenue for cardiovascular therapy, providing a platform for combined drug delivery and potential synergistic effects. The optimized formulation could lead to improved patient outcomes and enhanced cardiovascular health.

Comparative analysis of the therapeutic efficacy of remimazolam tosylate and propofol in older adults undergoing painless endoscopic retrograde cholangiopancreatography.

The aim of this study is to conduct a comparative analysis of the therapeutic outcomes associated with the administration of remimazolam and propofol during painless endoscopic retrograde cholangiopancreatography (ERCP) procedures in older adults. A total of 140 older adults who underwent elective painless ERCP were randomly assigned to two groups using the random number table method: the remimazolam group and the propofol group, each consisting of 70 patients. In the remimazolam group, anesthesia was administered using a combination of remimazolam and opioids, while in the propofol group, a combination of propofol and opioids was used. Comparative assessments between the two groups included anesthesia induction time, first induction success rate, intraoperative hemodynamics, awakening duration, stress response index, and the incidence of adverse reactions. The remimazolam group exhibited a prolonged anesthesia induction time compared to the propofol group and a lower success rate of first induction (P < 0.05). At the point of endoscope entry (T2) and 10min post-operation (T3), patients in the remimazolam group demonstrated higher mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) values compared to those in the propofol group (P < 0.05). Furthermore, the remimazolam group had shorter durations for eye-opening, consciousness recovery, and residence in the recovery room compared to the propofol group (P < 0.05). Post-surgery levels of epinephrine (E), norepinephrine (NE), and cortisol (Cor) at 24h were lower in the remimazolam group than in the propofol group (P < 0.05). The incidence of adverse reactions was significantly lower in the remimazolam group (18.57%) compared to the propofol group (31.43%) (P < 0.05). Remimazolam exhibits a longer induction time compared to propofol in the painless diagnosis and treatment of ERCP in older adults. However, it provides a more stable circulatory state post-induction and throughout the operation, reduces stress response, enables rapid recovery, and has a lower incidence of serious adverse reactions. These attributes suggest that remimazolam has potential for widespread clinical application and adoption. clinicaltrials.gov, identifier ChiCTR2400080926.

Effects of glucagon-like peptide-1 receptor agonists on blood pressure in overweight or obese patients: a meta-analysis of randomized controlled trials.

Glucagon-like peptide-1 receptor agonists are novel medications with proven efficacy in treating type 2 diabetes mellitus, and are increasingly being used for weight loss. They may potentially have benefit in treating metabolic disorders; however, evidence is sparse with regards to treating high blood pressure (BP). We performed a systematic review, meta-analysis and meta-regression investigating the efficacy of GLP-1 RAs in lowering BP in obese or overweight patients. Three electronic databases (PubMed, EMBASE, and CENTRAL) were systematically searched for randomized controlled trials (RCTs) published from inception to 13 February 2024. Pair-wise meta-analysis and random effects meta-regression models were utilized. Fixed effects meta-regression was used to unify treatment effects across different GLP-1 RA doses. We included a total of 30 RCTs with a combined population of 37 072 patients. GLP-1 RAs demonstrated a mean systolic BP (SBP) reduction of -3.37 mmHg [95% confidence interval (CI) -3.95 to -2.80] and a mean diastolic BP (DBP) reduction of -1.05 mmHg (95% CI -1.46 to -0.65) compared with placebo. This effect was consistent across subgroups for diabetic status, formulation of GLP-1 RA, follow-up duration and route of administration for both SBP and DBP, with the exception of subgroups investigating exenatide. Meta-regression suggested no significant correlation between BP reduction and baseline characteristics such as age, percentage of male patients, HbA1c, weight, BMI, and percentage of patients with hypertension. Our meta-analysis suggests significant BP reduction benefits from GLP-1 RA use in obese or overweight patients, consistent across diabetic status, duration of treatment, and across route of administration.

Muscle Oxygen Saturation Dynamics During Upper-Body Resistance Exercise

Research examining the changes in muscle oxygen saturation across multiple sets of resistance exercise is limited. The purpose of this study was to describe the physiological response of muscle oxygenation parameters during upper-body resistance exercise and examine the differential effects of relevant participant characteristics on resistance training performance and muscle oxygen saturation dynamics. Sixty-one recreationally trained men (n = 44; 21.8 ± 2.6 years) and women (n = 17; 20.2 ± 1.8 years) completed five-repetition maximum sets of barbell bench presses at a load equal to 75% 1-RM with a 2 min rest interval. Muscle oxygen saturation (SmO2) dynamics within the anterior deltoid were monitored using a portable near-infrared spectroscopy sensor. The percent change in SmO2 (∆%SmO2), the muscle oxygen re-saturation rate (SmO2RecSlope), and the highest measured SmO2 value during recovery periods (SmO2Peak) were measured. Two-way (sex [men, women] x time [sets 1–5]) repeated measures analyses of variance (ANOVA) were performed on muscle saturation variables. To examine the effect of relevant controlling variables, separate analyses of covariance (ANCOVA) with repeated measures were also performed. No differences were seen with ∆%SmO2 across sets. The main effects for sets occurred for SmO2RecSlope, whereby a decline was noted on sets 4 and 5 (p = 0.001) compared to set 1. Additionally, SmO2Peak was the lowest on set 5 (p &lt; 0.001) compared to all other sets. Moreover, body mass (p = 0.013), diastolic blood pressure (p = 0.044), and mean arterial pressure (p = 0.033) for ∆%SmO2 were the only significant covariates noted amongst the muscle oxygenation variables. In conclusion, no sex differences and only a few set differences in muscle oxygen saturation dynamics were seen without employing any covariates. Body mass, diastolic blood pressure, and mean arterial pressure were identified as factors that could influence observed responses.

Reinforcement Learning to Optimize Ventilator Settings for Patients on Invasive Mechanical Ventilation: Retrospective Study.

One of the significant changes in intensive care medicine over the past 2 decades is the acknowledgment that improper mechanical ventilation settings substantially contribute to pulmonary injury in critically ill patients. Artificial intelligence (AI) solutions can optimize mechanical ventilation settings in intensive care units (ICUs) and improve patient outcomes. Specifically, machine learning algorithms can be trained on large datasets of patient information and mechanical ventilation settings. These algorithms can then predict patient responses to different ventilation strategies and suggest personalized ventilation settings for individual patients. In this study, we aimed to design and evaluate an AI solution that could tailor an optimal ventilator strategy for each critically ill patient who requires mechanical ventilation. We proposed a reinforcement learning-based AI solution using observational data from multiple ICUs in the United States. The primary outcome was hospital mortality. Secondary outcomes were the proportion of optimal oxygen saturation and the proportion of optimal mean arterial blood pressure. We trained our AI agent to recommend low, medium, and high levels of 3 ventilator settings-positive end-expiratory pressure, fraction of inspired oxygen, and ideal body weight-adjusted tidal volume-according to patients' health conditions. We defined a policy as rules guiding ventilator setting changes given specific clinical scenarios. Off-policy evaluation metrics were applied to evaluate the AI policy. We studied 21,595 and 5105 patients' ICU stays from the e-Intensive Care Unit Collaborative Research (eICU) and Medical Information Mart for Intensive Care IV (MIMIC-IV) databases, respectively. Using the learned AI policy, we estimated the hospital mortality rate (eICU 12.1%, SD 3.1%; MIMIC-IV 29.1%, SD 0.9%), the proportion of optimal oxygen saturation (eICU 58.7%, SD 4.7%; MIMIC-IV 49%, SD 1%), and the proportion of optimal mean arterial blood pressure (eICU 31.1%, SD 4.5%; MIMIC-IV 41.2%, SD 1%). Based on multiple quantitative and qualitative evaluation metrics, our proposed AI solution outperformed observed clinical practice. Our study found that customizing ventilation settings for individual patients led to lower estimated hospital mortality rates compared to actual rates. This highlights the potential effectiveness of using reinforcement learning methodology to develop AI models that analyze complex clinical data for optimizing treatment parameters. Additionally, our findings suggest the integration of this model into a clinical decision support system for refining ventilation settings, supporting the need for prospective validation trials.

Decompensated MASH-Cirrhosis Model by Acute and Toxic Effects of Phenobarbital.

Metabolic dysfunction-associated Steatohepatitis (MASH), is a prominent cause for liver cirrhosis. MASH-cirrhosis is responsible for liver complications and there is no specific treatment. To develop new therapeutic approaches, animal models are needed. The aim of this study was to develop a fast animal model of MASH-cirrhosis in rats reflecting the human disease. Carbon tetrachloride (CCl4) injections in combination with a high-fat Western diet (WD) were used to induce MASH-cirrhosis. To accelerate liver injury, animals received phenobarbital (PB) in their drinking water using two different regimens. Rats developed advanced MASH-cirrhosis characterized by portal hypertension, blood biochemistry, hepatic ballooning, steatosis, inflammation and fibrosis. Importantly, rats receiving low-dose PB for the long term (LT) showed ascites after 6 weeks, whereas rats with high-dose short-term (ST) PB developed ascites after 8 weeks. ST- and LT-treated rats showed increased portal pressure (PP) and decreased mean arterial pressure (MAP). Of note, hepatocyte ballooning was only observed in the LT group. The LT administration of low-dose PB with CCl4 intoxication and WD represents a fast and reproducible rat model mimicking decompensated MASH-cirrhosis in humans. Thus, CCl4 + WD with LT low-dose phenobarbital treatment might be the preferred rat animal model for drug development in MASH-cirrhosis.

Chronic kidney disease in Kuwait: a multicenter study of two cohorts with different levels of access to public healthcare

IntroductionKuwait has a large expatriate community who experience both restricted access to public health services and lower income than Kuwaiti citizens. Given these conditions, we examined differences in characteristics and management of chronic kidney disease (CKD) between Kuwaitis and expatriates.MethodsClinical and laboratory data for adult CKD Stages 3–5 not on dialysis (CKD 3–5 ND) patients with native kidneys attending nephrology clinics in all Ministry of Health hospitals collected from January 1, 2022, to December 31, 2022. Cohort was then divided into Kuwaiti patients and expatriates patients for comparison.ResultsWe collected data from 2,610 patients (eGFR: 30.8 ml/min/1.73m2; age: 62.6 years; males: 56.7%; Kuwaitis: 62.1%). Kuwaitis were older (63.94 vs. 60.3 years, p < 0.001), with lower mean eGFR (30.4 vs. 31.5 ml/min/1.73m2, p = 0.052) than non-Kuwaitis, however, Kuwaitis had lower mean blood pressure (137.2/76.5 vs. 139.1/78.9 mmHg, p = 0.006), lower HbA1c in diabetics (7.59 vs. 7.82%, p = 0.010), and better lipid profile despite higher body mass indexes (29.6 vs. 28.9 kg/m2, p = 0.002). Both groups had high diabetes mellitus and hypertension rates. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were used in only 22.6% and renin-angiotensin-aldosterone system inhibitors (RAASi) in only 46.2%.ConclusionCKD 3–5 ND is caused by diabetes mellitus in 56.6% of cases, and the majority have hypertension. In our study, non-Kuwaitis had higher eGFR; however, restricted public healthcare access and lower income can lead to an unhealthy diet and suboptimal care, which may cause higher blood pressure, higher HbA1c, and a higher dyslipidemia rate. RAASi and SGLT2i utilization must increase to combat CKD, and antihypertensive selection must improve.

Effect of Aerobic Exercise with Blood Flow Restriction on Postexercise Hypotension in Young Adults: The Role of Histamine Receptors.

We tested hypothesis that aerobic exercise with blood flow restriction (BFR) induced postexercise hypotension (PEH), and the reduction in blood pressure (BP) was due to peripheral vasodilation via the histamine receptors. Ten male subjects participated in this study. The subjects were randomly assigned to walk for 10 min at 6.4 km/h, 0% grade with or without BFR after taking histamine receptor blockade. Following exercise, BP was measured at 10 min interval for 60 min. Heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), and total peripheral resistance (TPR) were evaluated. Our results indicated that MAP was significantly lowered immediately after exercise at 20 min, 30 min, and 40 min before the blockade as opposed to after the blockade. A significant reduction in diastolic BP (DBP) occurred. There were no significant differences in HR, SV, CO, and TPR between before the blockade and after the blockade. MAP was substantially decreased at 20 min, 30 min, and 40 min before the blockade compared to resting (-3.2 ± 2.2, -3.3 ± 2.8, and -2.9 ± 2.5, respectively) while increasing MAP after the blockade. The current study demonstrated that low-intensity aerobic exercise with BFR lowered MAP via histamine receptor-induced peripheral vasodilation. In conclusion, BFR exercise training using short periods and low intensity would be greatly beneficial as a potential treatment to lower BP.

Prediction of poor prognosis using the peak systolic velocity and early diastolic velocity of the central retinal artery in patients with post‐cardiac arrest syndrome

AbstractIntroductionMonitoring intracranial pressure (ICP) in patients with post‐cardiac arrest syndrome (PCAS) is crucial for effective management and prognosis assessment. However, continuous ICP monitoring is rarely practiced. Increased ICP is often associated with the impairment of brain autoregulation. This study investigated whether central retinal artery (CRA) flow velocity, autoregulation status according to mean arterial pressure (MAP), and the optic nerve sheath diameter (ONSD)/eyeball transverse diameter (ETD) ratio could predict poor prognosis related to increased ICP in PCAS patients.MethodsIn this multicenter prospective observational study, transocular ultrasonography of the optic nerve sheath was performed on 38 PCAS patients treated with targeted temperature management from December 2021 to November 2022. CRA peak systolic velocity (PSV), early diastolic velocity (eDV), MAP, CRA‐PSV changes following MAP changes (autoregulation), and ONSD/ETD ratio were measured repeatedly from days 0 to 4 post‐admission.ResultsUnivariable analysis indicated that CRA‐PSV, nonpositive or flat CRA‐eDV, and disrupted autoregulation correlated with a poor prognosis (Cerebral Performance Category 4 or 5). In multivariable analysis, nonpositive CRA‐eDV or disrupted autoregulation was the most significant predictor of poor prognosis (odds ratio, 40.576; p = 0.002), with an area under the curve of 0.774. The ONSD/ETD ratio did not show a significant correlation.ConclusionsNonpositive CRA‐eDV, CRA‐PSV and disrupted autoregulation can predict poor prognosis in PCAS patients. Transocular Doppler ultrasonography of the CRA and autoregulation assessment may aid in ICP monitoring and management in PCAS patients.

An Observational Study on Clinical Benefits of CytoSorb in Patients with Severe Sepsis

Background and Aim: Sepsis is a well-recognized healthcare issue worldwide. Despite research, the ability to positively influence outcome remains limited. Newer evidences have pointed that using adsorption of cytokines is beneficial during endotoxemia and sepsis. Therefore, this study was aimed to determine the clinical benefits of CytoSorb usage in patients with severe sepsis admitted in intensive care units (ICU). Study Design: Prospective, observational, comparative study. Material and Methods: Forty patients with sepsis admitted to ICU were included. The CytoSorb group included 20 patients who received CytoSorb therapy in addition to Standard-care (SOC) and 20 patients in SOC group who received SOC alone as per routine ICU protocols. Clinical and laboratory parameters were analyzed pre/post-treatment in both groups and compared. Results: CytoSorb and SOC groups were comparable at baseline. There was significant reduction in serum creatinine (2.59±2.0 vs. 2.89±1.2, mg/dl; P=0.042), serum lactate (3.26±1.1 vs. 3.27±0.9, mmol/lit; P&lt;0.001), serum procalcitonin (2.75±2.4 vs. 3.39±3.5, ng/ml; P&lt;0.001), serum CRP (90.2±57.4 vs. 175.6±100.9, mg/dl; P&lt;0.001) and serum IL6 (1769.7±4444.1 vs. 256.8±392.4, pg/ml; P=0.03) levels in CytoSorb compared to SOC. There was significant improvement in mean arterial pressure (MAP) (65.75±1.8 vs. 62.75±2.8, mmHg; P&lt;0.001) and reduction in norepinephrine dose (6.47±2.7 vs.10.65±3.6, mcg/min; P&lt;0.001) in CytoSorb group reflecting better hemodynamic stability. The post-treatment increase in SOFA score was lesser in CytoSorb group (11.85±2.9) than SOC group (12.3±2.3), but was not significant (P=0.135). Conclusion: CytoSorb therapy along with SOC was associated with significant improvements in hemodynamic stability, MAP and Norepinephrine requirements than SOC alone in severe sepsis.

The correlation between mental health and arterial stiffness in Chinese population

This study aimed to evaluate the correlation between mental health status and arterial stiffness. A Symptom Checklist 90 (SCL-90) score was conducted for 10,688 employees of Kailuan Group Co., Ltd., of which 4936 participants received baPWV measurement. Of these, 4424 met the inclusion criteria. Based on the SCL-90 score, the study subjects were divided into normal mental health group (SCL-90 score < 160, 3993 cases) and abnormal mental health group (SCL-90 score ≥ 160, 431 cases). Statistical indicators include: General information, including levels of brachial-ankle pulse wave velocity (baPWV), age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), body mass index (BMI), smoking and alcohol consumption, daily activity levels, nature of work and educational qualifications. The proportion of males, baPWV value, and abnormal proportion of baPWV in normal mental health group were higher than those in abnormal mental health group (P < 0.05). The Hs-CRP in normal mental health group were lower than that in abnormal mental health group (P < 0.05). There were significant differences in activity level and educational attainment between the two groups (P < 0.05). After adjusting for confounders, the results of the multiple linear regression analysis showed that, Age, MAP, HR, FBG, TG were positively correlated with baPWV; SCL-90 score, gender, BMI, educational qualification were negatively correlated with baPWV. When the SCL-90 score of the general population increased by one point, baPWV decreased by 0.246 cm/s. Each such increase corresponded with a decrease in baPWV of 0.299 cm/s for male participants in general (β = − 0.299, P = 0.007) and 0.412 cm/s for the male participants in the older-age group (β = − 0.412, P = 0.017). Although adverse psychological factors have a certain impact on arterial stiffness, it does not constitute an independent risk factor.

Niclosamide attenuates erectile dysfunction and corporal fibrosis via reversal of Smad signaling in diabetic rat model.

Diabetes mellitus-induced erectile dysfunction (DMED) is a common urological complication of diabetes, and current drugs often fail to provide an effective treatment. Smad2/3 signaling-mediated corporal fibrosis has a critical role in the molecular basis of DMED. We investigated the effect of Niclosamide (Nic), an antihelmintic drug with antifibrotic effects, on erectile function in a rat DMED model. Male Sprague Dawley rats were injected intraperitoneally (i.p) with streptozotocin (75mg/kg) to induce diabetes. At week 8, both diabetic and nondiabetic rats were treated with Nic (10mg·kg-1/day; i.p) or vehicle for 4weeks. At week 12, erectile function was evaluated as intracavernous pressure (ICP) response to the electrical stimulation of the cavernous nerve (CN). Penile tissues were harvested for Masson's trichrome staining or western blotting to determine corporal fibrosis and Smad2/3 pathway-related protein expression, respectively. At the end of the experimental protocol, in vivo erectile function was assessed by measuring the ratio of ICP/ mean arterial pressure (MAP) and total ICP following CN stimulation. Smooth muscle content and collagen fibers were evaluated by Masson's trichrome staining of the penile tissues. The expressions of fibrosis-related proteins (Smad2, Smad3, fibronectin) were determined using western blotting in the penile tissues. Erectile function, as determined by the maximum ICP/MAP and total ICP/MAP ratios, was drastically decreased in diabetic rats. Corporal tissues of diabetic rats were severely fibrotic with a significant increase in collagen fibers and a marked reduction in smooth muscle content. Also, the protein expressions of phosphorylated (p-)Smad2, p-Smad3 and fibronectin were significantly increased in the penis of diabetic rats. Both functional and molecular alterations in DMED were effectively reversed by Nic-treated diabetic rats without a glycemic alteration. Nic could be a promising candidate for the treatment of DMED due to its antifibrotic effects. The present study provides the first evidence that Nic has beneficial effect on erectile dysfunction by attenuating corporal fibrosis in a rat model of DMED. The effect of Nic on penile endothelial function and the other potential underlying mechanisms needs to be further elucidated. Nic improved erectile function in DMED rats possibly suppressing penile fibrosis by inhibiting Smad2/3 signaling. These results suggest a potential therapeutic repurposing of Nic as an adjuvant treatment in DMED.

Pilot study for non-invasive diabetes detection through classification of photoplethysmography signals using convolutional neural networks

Diabetes is a chronic disorder affecting vascular health, often altering pulse wave characteristics. Traditional pulse wave analysis (PWA) methods face challenges such as variability and complexity of signals. This study aims to overcome these limitations by leveraging deep learning models for more accurate and efficient classification. The methodology used in this study involves four key steps: data collection, data preprocessing, Convolutional Neural Network (CNN) model development, and model evaluation. Primary data were collected using a multipara patient monitor, including finger photoplethysmography (PPG) signals, blood pressure, mean arterial pressure, oxygen saturation, and pulse rate. Single pulse wave cycles from 60 healthy individuals and 60 patients with type 2 diabetes underwent preprocessing. The CNN model was trained using 50 PPG images from each group and achieved a training accuracy of 92%. The prediction capability of the model was evaluated using 20 unseen images, comprising 10 healthy and 10 diabetes PPG images. It attained a 90% overall test accuracy in distinguishing between PPG images of individuals with diabetes and those who are healthy. These findings suggest that CNN-based analysis of PPG signals provides a precise, non-invasive tool for diabetes screening. To further enhance accuracy, future studies should focus on increasing the dataset size and performing hyperparameter tuning to optimize the CNN model.

Exploring the repeatability of pulse arrival time in healthy subjects: A test-retest approach

Objectives: Vascular ageing is increasingly being recognised as a vital marker of cardiovascular morbidity and mortality. Assessment of vascular stiffness is an important parameter in this context. Pulse arrival time (PAT) assessed using photoplethysmography (PPG) and digital electrocardiogram (ECG) signals is a feasible and cost-effective parameter for this assessment. However, there are few, if any, studies that have assessed the test-retest repeatability of this parameter over time. Materials and Methods: We computed PAT using finger PPG and Lead II ECG and measured it sequentially at five instances over a period of 1 month in 21 healthy adults (10 males and 11 females). Mean and diastolic blood pressure (MBP and DBP) and heart rate (HR) were also measured at each visit. A novel parameter, PAT normalised for HR of 75 (PAT-75), was also computed. PAT and PAT-75 were compared for these visits using repeated measures analysis of variance. The intraclass correlation coefficient (ICC) was used to assess the test-retest reliability of this parameter. Results: MBP, DBP, and PAT values did not show any difference between the visits. HR was significantly different between the visits. PAT-75 was significantly lower for the afternoon of day 1 as compared to the forenoon. ICC demonstrated only moderate reliability of PAT (ICC = 0.57), with further reduction observed for PAT-75 (ICC = 0.38). Conclusion: PAT was only moderately repeatable on repeated evaluation over a 1-month period. This finding may have implications for the large-scale applicability of this technology, and therefore, we propose further investigation into the repeatability of this parameter in large cohorts.

Impact of glossopharyngeal insufflation and complete exhalation on breath-hold performance and physiological parameters in elite skin divers.

This study examined the physiological responses of ten elite divers to normal breathing (BHn), glossopharyngeal inhalation (BHi), and complete exhalation (BHe) prior to five maximal breath-hold (BH) efforts. Breath-hold time (BHT), hemological variables, mean arterial pressure (MAP), other hemodynamic indices, and diaphragmatic activity (DA) were recorded. During BHs, phases were identified as easy-going (EPh: minimal DA), struggling (SPh: increased DA), PhI (MAP transition), PhII (MAP stabilization), and PhIII (steep MAP increase). BHi significantly extended BHT (309.14 ± 12.91s) compared to BHn (288.77 ± 10.99s) and BHe (151.18 ± 10.94s) (P = 0.001). BHT, EPh, and SPh in BHi increased by 7.05%, 2.57%, and 11.08% over BHn, respectively. PhIII appeared earlier in BHe than in other conditions (P < 0.001) and accounted for 47.07%, 44.96%, and 60.18% of BHT in BHn, BHi, and BHe, respectively. SPh comprised 47.10%, 46.01%, and 45.13% of BHT in BHn, BHi, and BHe, respectively, with SPh onset coinciding with PhIII onset in BHn and BHi but not in BHe. Bradycardia was more pronounced in BHe, maintaining better stroke volume. No significant differences in red blood cells or maximal MAP were noted across conditions. Glossopharyngeal inhalation improves BHT and extends EPh and SPh durations. PhIII onset is linked to SPh in BHn and BHi but not in BHe. BHe triggers an earlier MAP rise, leading to stronger parasympathetic responses. Despite similar maximal MAP across conditions, the higher BHT and tissue hypoxemia in BHi and BHn suggest MAP is a key limiting factor in apnoea.

Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol-SEPSIS-BRAIN.

Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607.

Association of serum Metrnl levels and high-density lipoprotein cholesterol in patients with type 2 diabetes mellitus: a cross-sectional study.

Meteorin-like (Metrnl) is a novel adipokine which is highly expressed in adipose tissue and has a beneficial effect on glucose and lipid metabolism. High density lipoprotein cholesterol (HDL-C) is well recognized to be inversely associated with cardiovascular events. However, the relationship between serum Metrnl levels and HDL-C in the type 2 diabetes mellitus (T2DM) remains unclear. Therefore, the present study aimed to evaluate the association of serum Metrnl with HDL-C levels in T2DM. Eighty participants with T2DM were included in this cross-sectional study. They were divided into two groups according to HDL-C levels: Group1 (lower HDL-C group): HDL-C < 1.04 mmol/L; Group2 (higher HDL-C group): HDL-C ≥ 1.04 mmol/L. Serum Metrnl levels were measured by enzyme-linked immunosorbent assay (ELISA). As compared with lower HDL-C levels groups, serum Metrnl levels were significantly higher in the group with higher HDL-C. Binary logistic regression analysis showed serum Metrnl levels were positively associated with HDL-C group after adjustment with sex, age, body mass index (BMI), mean arterial pressure (MAP), fasting blood glucose (FPG), triglyceride (TG). Furthermore, serum Metrnl levels were inversely correlated with insulin resistance index (HOMA-IR). HDL-C levels were lowest in the group with the lowest Metrnl levels group and remained positively associated with Metrnl after adjustment for sex, age, BMI, TG, and HOMA-IR by using multivariate logistic regression analysis. Serum Metrnl levels were positively associated with HDL-C levels in patients with T2DM.This suggests that increasing serum Metrnl levels maybe a candidate for improving lipid metabolism and preventing cardiovascular events in T2DM. The study was registered in the Chinese clinical trial registry (ChiCTR- 2100047148).

Body composition as a potential imaging biomarker for predicting the progression risk of chronic kidney disease

PurposeTo investigate whether the body composition parameters can be employed as potential biomarkers for predicting the progression risk of chronic kidney disease (CKD).Materials and methodsFour hundred sixteen patients diagnosed with CKD were included in this retrospective study. Patients with a greater than 50% decline in estimated glomerular filtration rate or progression to end-stage kidney disease were in the high-risk group, otherwise, they were in a low-risk group. Body composition area, the index, and radiodensities in the Hounsfield unit (HU), which reflect the degree of X-ray absorption, were measured on abdominal CT images. Risk factors in body composition and clinical parameters of CKD were identified by Cox regression and utilized to construct the nomogram. The performance of the nomogram was assessed using time receiver operating characteristics curves, calibration curves, and decision curve analysis.ResultsThere were 254 patients in low-risk group and 162 in high-risk group (268 males, 148 females, mean age: 55.89 years). Urea, diabetes, 24 h-urinary protein, mean arterial pressure, and subcutaneous adipose tissue radiodensity (SATd) were valuable indicators for predicting the high-risk group. The area under curve values for the nomogram of training/validation set at 1 year, 2 years, and 3 years were 0.805/0.753, 0.784/0.783, and 0.846/0.754, respectively. For diabetic CKD patients, extra attention needs to be paid to visceral to subcutaneous fat ratio and renal sinus fat radiodensity.ConclusionSATd was the most valuable noninvasive indicator of all body composition parameters for predicting high-risk populations with CKD. The nomogram we constructed has generalization with easily obtainable indicators, good performance, differentiation, and clinical practicability.Critical relevance statementRadiodensity rather than an area of adipose tissue can be used as a new biomarker of prognosis for CKD patients, providing new insights into risk assessment, stratified management, and treatment for CKD patients.Key PointsObesity is an independent risk factor for the development and prognosis of CKD.Adipose tissue radiodensity is more valuable than fat area in prognosticating for kidney disease.Parameters that prognosticate in diabetic CKD patients are different from those in other CKD patients.Graphical

Imminent risk of LVEF decline in asymptomatic patients with primary mitral regurgitation.

2020 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines state that the ideal time for mitral valve surgery in primary mitral regurgitation (PMR) is when the LV approaches but has not yet reached echocardiographic LV ejection fraction (EF) < 60% or LV end-systolic dimension (ESD) > 40 mm. However, it is difficult to know the imminent risk of crossing this threshold when the surgical outcome is less optimal. Using machine learning and statistical models, we have shown that cardiac magnetic resonance (CMR) LV sphericity index (SI) and LV mid circumferential strain rate (SRcirc) added to LVEF and LVESD predict LVEF < 50% after mitral valve surgery. Here we test the hypothesis that these CMR features predict LVEF < 60% in asymptomatic PMR patients at 18 months. 33 asymptomatic PMR patients with moderate to severe mitral regurgitation had CMR with tissue tagging at baseline and every 6 months for 18 months. Two types of models were employed to predict LVEF < 60% at 18 months: a model using CMR features at a single time point (e.g., baseline) and a model utilizing repeated measurements over time. CMR LVEF decreased below 60% in 13 patients over 18 months. LVEF varied over time with an inverse relation to mean arterial pressure and mean end-systolic wall stress. Random Forest models utilizing LV SI, LV mid SRcirc, LVESD, and LVEF at a single time point (baseline) had a predictive accuracy of 64%. LV SI, LV mid SRcirc, LVESD and LVEF at baseline, 6, and 12 months achieved a higher predictive accuracy of 79%, improved sensitivity from 57% to 85% than baseline alone and identified a threshold of CMR LVEF 63%-64% signaling LVEF < 60%. The variability of LVEF due to blood pressure dependence may require a longitudinal study that incorporates LVEF, LVESD, SRcirc at multiple time points to identify the threshold at which LVEF is at risk for decline to less than 60%.

Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study

Chronic kidney disease (CKD) affects ~10% of the population and cardiovascular disease is its commonest complication. Despite treatment, patient outcomes remain poor and newer therapies are urgently needed. Here, we investigated the systemic and renal effects of apelin in CKD. In a randomized, double-blind, placebo-controlled, crossover study, 24 subjects (12 patients with CKD and 12 matched healthy subjects) received pyroglutamated apelin-13 ([Pyr1]apelin-13, 1 nmol/min and 30 nmol/min) or matched placebo on two separate visits. Systemic and renal hemodynamics were monitored throughout. The co-primary endpoints were change in systemic vascular resistance index and renal blood flow. Secondary endpoints were change in blood pressure, cardiac output, pulse wave velocity, glomerular filtration rate, natriuresis, free water clearance and urinary protein excretion. In both health and CKD, 30 nmol/min [Pyr1]apelin-13 reduced mean arterial pressure by ~4%, systemic vascular resistance by ~12%, and increased cardiac index by ~10%, compared to placebo (p < 0.05 for all). Both doses of [Pyr1]apelin-13 increased renal blood flow by ~15%, natriuresis by ~20% and free water clearance by ~10%, compared to placebo (p < 0.05 for all). In patients with chronic kidney disease only, glomerular filtration rate fell by ~10%, effective filtration fraction by ~5% and proteinuria by ~25% (p < 0.01 for all). Apelin has short-term cardiovascular and renal benefits in CKD. If maintained longer-term, these should improve patient outcomes. Clinical trials of long-acting oral apelin agonists are justified in CKD and other conditions with impaired salt and water balance. Registration number at www.clinicalTrials.gov: NCT03956576. Funded by Kidney Research UK.