Pressure Regulation Research Articles

Continuous cuff pressure control on middle-aged and elderly patients undergoing endoscopic submucosal dissection of the esophagus effect of airway injury.

Assessment of the effect of continuous cuff pressure control on airway injury in middle-aged and elderly patients undergoing endoscopic submucosal dissection (ESD). A total of 104 eligible middle-aged and elderly patients requiring esophageal ESD from July 2022-September 2023 at the First Affiliated Hospital of Nanchang University were selected and randomly divided into two groups: the group undergoing general anesthesia tracheal intubation with continuous control of cuff pressure after intubation (Group A, n = 51) and the group undergoing general anesthesia tracheal intubation with continuous monitoring without control of cuff pressure (Group B, n = 53). After endotracheal intubation in Group A, under the guidance of an automatic cuff pressure controller, the air was used to inflate the tracheal cuff until the cuff pressure was 25-30cmH2O. The cuff pressure after intubation was recorded, and then the cuff pressure parameters were directly adjusted in the range of 25-30cmH2O until tracheal extubation after the operation. After endotracheal intubation, patients in Group B inflated the tracheal cuff with clinical experience, then monitored and recorded the cuff pressure with a handheld cuff manometer and instructed the cuff not to be loosened after being connected to the handheld cuff manometer-continuous monitoring until the tracheal extubation, but without any cuff pressure regulation. The patients of the two groups performed esophageal ESD. The left recumbent position was taken before the operation, and the cuff's pressure was recorded. Then, insert the gastrointestinal endoscope to find the lesion site and perform appropriate CO2 inflation to display the diseased esophageal wall for surgical operation fully. After determining the location, the cuff pressure of the two groups was recorded when the cuff pressure was stable. After the operation, the upper gastrointestinal endoscope was removed and the cuff pressure of the two groups was recorded. Postoperative airway injury assessment was performed in both groups, and the incidence of sore throat, hoarseness, cough, and blood in sputum was recorded. The incidence of postoperative airway mucosal injury was also observed and recorded in both groups: typical, episodic congestion spots and patchy local congestion. The incidence of normal airway mucosa in Group A was higher than that in Group B (P < 0.05). In comparison, the incidence of occasional hyperemia and local plaque congestion in Group A was lower than in Group B (P < 0.05). Continuous cuff pressure control during operation can reduce airway injury in patients with esophageal ESD and accelerate their early recovery after the operation.

The pressure field model: a challenge to the conventional Starling and Guyton model of hemodynamic management

IntroductionEnsuring hemodynamic stability with adequate perfusion to vital organs is critical to the safe conduct of anesthesia. Recent advances in hemodynamic monitoring technologies allow pressure, flow, and resistance to be measured continuously; however, there is limited evidence to suggest that these technologies alter clinical management or improve patient outcomes significantly. This may be because the fundamental hemodynamic model, established by Starling and Guyton, fails to offer the granular level of insight needed to guide clinical management.MethodsWe collected hemodynamic data from 950 patients who underwent major surgery with advanced hemodynamic monitoring (AHM) that provided continuously derived cardiac output and vascular resistance measurements. These measurements were based on the hemodynamic model of Starling and Guyton. Additionally, investigational monitoring software was developed to visualize a different hemodynamic model, termed the “pressure field” model. This model expresses the pulsatile, beat-to-beat relationship between ventricular performance (measured by stroke volume) and vascular tone (indicated by systemic elastance).ResultsWithin this dataset were several patients who experienced major hemorrhage. Case studies of these patients demonstrate that abnormal pressure and flow regulation patterns are observed through the lens of the pressure field model, but these patterns are typically not visible through the lens of the traditional Starling and Guyton model (cardiac output and systemic vascular resistance, which involve averaging hemodynamic performance over successive cardiac cycles). Furthermore, “before and after” case studies using our investigational pressure field monitoring software suggest that the traditional Starling and Guyton hemodynamic model has limited utility in managing hemorrhage.DiscussionWe propose that the pressure field model may allow hemorrhage to be managed more effectively via improved monitoring granularity [the beat-by-beat visualization of the stroke volume-systemic elastance relationship, rather than the use of the composite metrics of cardiac output (heart rate × stroke volume) and systemic vascular resistance]. Further research into the utility of the pressure field model is warranted.

Second Harmonic Generation in β-K2TeW3O12: An Acentric Crystal Designed from Centric Phase via Pressure Modulation.

The latent value of nonlinear optical (NLO) crystals applied in solid-state laser equipment necessitates the development of applicable strategies for constructing noncentrosymmetric (NCS) crystals. By modulating the synthetic temperature and pressure to achieve the rearrangement of [TeO3]2- groups, a new NCS tellurium tungstate, β-K2TeW3O12 (β-KTW), with a strong second harmonic generation (SHG) response was synthesized based on its centrosymmetric polymorphic phase α-K2TeW3O12 (α-KTW). Computational calculation reveals that the large SHG response of β-KTW (15 × KH2PO4@1064 and 1.5 × KTiOPO4@1950 nm) could be attributed to the uniform arrangement of the NLO-active [TeO3]2- and [WO6]6- groups. β-KTW also exhibits enlarged birefringence (0.196@1064 nm) and a high laser damage threshold (42.3 MW cm-2), showing great potential as a nonlinear crystalline material. This work also provides a new route for the construction of NLO crystals based on centric structure, i.e., reverse pressure regulation.

Environmental Cadmium Exposure Induces an Increase in Systolic Blood Pressure by Its Effect on GFR

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with hypertension, but the mechanism by which it raises blood pressure is not understood. We hypothesize that exposure to Cd reduces the glomerular filtration rate (GFR), which in turn causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes, and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73 m2 (low eGFR). More than half (58.8%) and 23.9% had moderate and severe tubular proteinuria, respectively. The mean blood and urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. Doubling of body burden of Cd increased the prevalence odds ratios (POR) for low eGFR and severe tubular proteinuria 41% and 48%, respectively. The POR for hypertension rose twofold in those with blood Cd levels of 0.61–1.69 µg/L or urinary Cd excretion levels ≥ 0.98 µg/g creatinine. In the hypertensive group, the eGFR was inversely associated with age (β = −0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). By mediation analysis, an increase in SBP was attributable totally to the effect of Cd on GFR. Thus, blood pressure appeared to rise as GFR fell. This finding is consistent with the well-known role of the kidney in long-term blood pressure regulation, and explains a universally high prevalence of hypertension among patients with low eGFR.

Аналіз впливу на прохідність автобронетанкової техніки конструктивних факторів та методика її збільшення шляхом автоматичного регулювання тиску повітря в шинах коліс

The purpose of the study is to analyze and determine the influence of various factors on the patency of armored vehicles (AMT) operated by the National Guard of Ukraine. Determination of the change in patency during the movement of AMT in different road and climatic conditions. Analysis of static and dynamic loads, which are characteristic of AMT movement over rough terrain, and their impact on the efficiency of the vehicle. The theoretical component of the study was carried out using mathematical modeling of the work process of regulating the air pressure in tires of AMT wheels, using the example of changes in the characteristics of adhesion coefficients with the supporting surface and rolling resistance depending on the change in pressure and load on the tires of the wheels when the AMT is moving off-road. As a result of mathematical modeling, the dependences of air pressure in tires of AMT wheels were obtained, depending on the coefficient of rolling resistance and the load on each of the wheels. Which, in turn, makes it possible to move to a sufficiently complete mathematical modeling of the movement of AMT on off-road, taking into account the reference cross-country ability. In the process of theoretical research, the structural parameters of the impact on the patency of AMT were analyzed quite completely, and a generalized comparative indicator of the patency parameters of vehicles was proposed. When analyzing it, it was found that the AMT tire and, specifically, the change in air pressure in it, have a significant impact on the bearing capacity. The authors propose to use the following evaluation criteria as criteria for assessing the efficiency of the passability when driving on deformable surfaces: a generalized comparative indicator of the parameters of the passability of vehicles. As a result of consideration of which, a significant influence on the patency parameters of the tires and directly the air pressure in them was established. Regulation and change of the air pressure in the tires of the wheels depending on the change in the coefficient of rolling resistance as well as the change in the load on each wheel, which are the ratio of the work that is spent on the traction force when overcoming different degrees of heaviness of the resistance of the supporting surfaces with the effect of deformation. And the load that falls on each of the AMT wheels allowed us to draw conclusions about the improvement of the regular tire pressure regulation system (RPRS) of the wheels.

In vitro inhibitor effect and molecular docking of thiamine (vitamin B1), riboflavin (vitamin B2), and reference inhibitor captopril on angiotensin-converting enzyme purified from sheep plasma

Objective Angiotensin-converting enzyme (ACE, EC 3.4.15.1) is a very important factor in the regulation of blood pressure. Also, the inhibition of ACE with natural compounds has been a very important research area in the treatment of high blood pressure. ACE was purified and characterized from sheep plasma. Molecular docking studies and the inhibition effect of thiamine, riboflavin, and captopril on ACE were investigated. Methods Herein, ACE was purified from sheep plasma by affinity chromatography. The effect of thiamine and riboflavin on ACE was researched. Molecular docking studies were performed to understand the molecular interactions between thiamine, riboflavin, and captopril with ACE. Results The purification coefficient was found to be 8636 fold. The binding energy of thiamine, riboflavin, and captopril was found to be -6.7 kcal/mol, -8.1 kcal/mol, and -5.5 kcal/mol, respectively. Thiamine conformed to three conventional hydrogen bonds with ASP:415, HIS:513, and LYS:454. Riboflavin formed four conventional hydrogen bonds with GLN:281, GLU:376, THR:282, and TYR:520. Captopril formed two conventional hydrogen bonds with ARG:124, one conventional hydrogen bond with TYR:62 and ASN:85, and one carbon-hydrogen bond with ASN:66. Molecular docking results showed that thiamine, riboflavin, and captopril interacted with ACE through hydrogen bonding and hydrophobic interactions. Thiamine and riboflavin indicated significant inhibition effects on ACE. The IC50 values of thiamine, riboflavin, and captopril were found as 960.56 µM, 11.02 µM, and 1.60 nM, respectively. Ki values for thiamine, riboflavin, and captopril were determined as 1352.04 µM, 12.30 µM, and 1.06 nM, respectively. Conclusion In this work, it was concluded that thiamine and riboflavin may have preventive and therapeutical impacts against high blood pressure with their ACE inhibitor effect. Thiamine and riboflavin showed a lower inhibitory effect with a higher IC50 than captopril. However, when the inhibitory effect of thiamine and riboflavin vitamins is compared to captopril, it is concluded that they may be natural inhibitors with fewer side effects.

First, a seat; then, an upgrade.

The Sir Stanley Peart Essay Competition is an annual event run by the British and Irish Hypertension Society to encourage Early Career Researchers to continue the ethos of Sir Stanley Peart. Sir Stanley Peart was a clinician and clinical researcher who made a major contribution to our understanding of blood pressure regulation. He was the first to demonstrate the release of noradrenaline in response to sympathetic nerve stimulation. He was also the first to purify, and determine the structure of, angiotensin and he later isolated the enzyme, renin, and carried out many important investigations of the factors controlling its release in the body. This year, the essay topic was "Do we need new classes of antihypertensive drugs?". In his prize-winning essay, "First, a seat; then, an upgrade", Dr Sathyanarayanan argues that we do not need new classes of antihypertensive drugs, instead we should focus our attention on addressing the factors that lead to high blood pressure in the first place and use our existing drug classes more effectively.

Optimizing Energy Efficiency and Environmental Sustainability in Gas Distribution Station: A Comprehensive Analysis and Technological Solutions

It is important to address the world‘s energy crisis, increasing energy demand and changing climate by finding ways to recover unused energy and minimise primary and secondary energy use and emissions. The natural gas sector, which consists of the transmission network and gas distribution stations, is an important part of the global and Lithuanian energy sector. However, due to the operating principle of gas pressure regulators, the energy potential of high-pressure gas is not efficiently utilized in gas distribution stations. As a result, natural gas boilers are used for gas preheating, and gas distribution stations cause additional environmental pollution. This study aims to find ways to optimise the efficiency of gas distribution stations and reduce their negative environmental impact by identifying areas where energy is wasted and proposing alternative technological solutions: turbine expander (as an alternative for gas pressure regulator), ground heat pumps, solar collectors and photovoltaic solar cells (as gas preheating alternatives). The best alternative technological solution for the gas distribution station is evaluated based on energy efficiency, economic viability, and environmental impact (3E criteria).

Optimizing Energy Efficiency and Environmental Sustainability in Gas Distribution Station: A Comprehensive Analysis and Technological Solutions

It is important to address the world‘s energy crisis, increasing energy demand and changing climate by finding ways to recover unused energy and minimise primary and secondary energy use and emissions. The natural gas sector, which consists of the transmission network and gas distribution stations, is an important part of the global and Lithuanian energy sector. However, due to the operating principle of gas pressure regulators, the energy potential of high-pressure gas is not efficiently utilized in gas distribution stations. As a result, natural gas boilers are used for gas preheating, and gas distribution stations cause additional environmental pollution. This study aims to find ways to optimise the efficiency of gas distribution stations and reduce their negative environmental impact by identifying areas where energy is wasted and proposing alternative technological solutions: turbine expander (as an alternative for gas pressure regulator), ground heat pumps, solar collectors and photovoltaic solar cells (as gas preheating alternatives). The best alternative technological solution for the gas distribution station is evaluated based on energy efficiency, economic viability, and environmental impact (3E criteria).

The Interaction of Vasopressin with Hormones of the Hypothalamo–Pituitary–Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water–electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo–pituitary–adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.

The Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases.

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.

Losing, regaining, and continuing to build self-confidence – a qualitative, phenomenological study of being physically active with a type B aortic dissection

Purpose To gain a comprehensive understanding of experiences related to being physically active in participants with an uncomplicated type B aortic dissection. Materials and methods We performed a qualitative, phenomenological study. First-person accounts of adults, who at least one year ago had an uncomplicated type B aortic dissection, were collected using semi-structured interviews. The audio recordings of the interviews were transcribed verbatim and analyzed with interpretative phenomenological analysis. Results We collected, in total, 644 min interview data from 14 participants. Three patterns were interpreted: losing self-confidence, regaining self-confidence, and continuing to build self-confidence. Experiencing symptoms when pushing limits, challenges with energy management, and side effects of medication caused loss of self-confidence. Changes in identity, reaching milestones that reflect improvement, and support from others and tools helped participants regain self-confidence. To continuing to build self-confidence, participants indicated they needed success experiences and activities make life worth living. Conclusions Self-confidence in adults with an uncomplicated type B aortic dissection changes immediately after the diagnosis of the aortic dissection. Rehabilitation professionals can support adults regaining and continuing to build self-confidence, aiming for the perfect balance between blood pressure regulation, quality of life, and being physically active. Implications for rehabilitation Rehabilitation professionals should support regaining and continuing to build self-confidence related to being physically active in adults with type B aortic dissection in the early stages of recovery and beyond. Adults with an uncomplicated type B aortic dissection want rehabilitation professionals to tell them primarily what is possible (recommendations) rather than what is not allowed (rules). Rehabilitation professionals should help adults with an uncomplicated type B aortic dissection to explore, push and, ultimately, accept limits related to exercise tolerance.

Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure

The kidney and brain play critical roles in the regulation of blood pressure. Neuropeptide FF (NPFF), originally isolated from the bovine brain, has been suggested to contribute to the pathogenesis of hypertension. However, the roles of NPFF and its receptors, NPFF-R1 and NPFF-R2, in the regulation of blood pressure, via the kidney, are not known. In this study, we found that the transcripts and proteins of NPFF and its receptors, NPFF-R1 and NPFF-R2, were expressed in mouse and human renal proximal tubules (RPTs). In mouse RPT cells (RPTCs), NPFF, but not RF-amide-related peptide-2 (RFRP-2), decreased the forskolin-stimulated cAMP production in a concentration- and time-dependent manner. Furthermore, dopamine D1-like receptors colocalized and co-immunoprecipitated with NPFF-R1 and NPFF-R2 in human RPTCs. The increase in cAMP production in human RPTCs caused by fenoldopam, a D1-like receptor agonist, was attenuated by NPFF, indicating an antagonistic interaction between NPFF and D1-like receptors. The renal subcapsular infusion of NPFF in C57BL/6 mice decreased renal sodium excretion and increased blood pressure. The NPFF-mediated increase in blood pressure was prevented by RF-9, an antagonist of NPFF receptors. Taken together, our findings suggest that autocrine NPFF and its receptors in the kidney regulate blood pressure, but the mechanisms remain to be determined.

Examination of role of the AMP-activated protein kinase (Ampk) signaling pathway during low salinity adaptation in the mud crab, Scylla paramamosain, with reference to glucolipid metabolism

It is known that the marine euryhaline crab, mud crab (Scylla paramamosain), is capable of adapting to low salinity conditions through an innate osmoregulatory system. However, the influence of nutritional conditions during low salinity adaptation has not been fully elucidated. In this study, transcriptome analysis was employed to examine whether low salinity affects the AMP-activated protein kinase (Ampk) signaling pathway, and thereby carbohydrate and lipid metabolism. Further analysis revealed that low salinity activated the expression of P-Ampk and promoted glycolysis and lipolysis, which enhances glycogen and lipid utilization. Nutritional deprivation confirmed that nutrients influenced the survival and osmotic pressure regulation of mud crab under to low salinity via the Ampk signaling pathway. During adaptation to low salinity, carbohydrates were the primary energy source in the initial 7 days, followed by lipids. Further investigation showed that pharmacological stimulation of mechanistic targets in the Ampk signaling pathway using metformin could promote the osmotic pressure regulation of mud crab, confirmed the pivotal role of this pathway in low salinity adaptation. Overall, the present study demonstrated that nutrition, metabolism and osmotic pressure regulation interactively contribute to salinity adaptation in mud crab. Specifically, low salinity induced remodeling of nutritional metabolism homeostasis and promoted glycolipid catabolism, thereby providing energy for osmotic pressure regulation in mud crabs.

Nursing interventions to prevent pressure injury among open heart surgery patients: A systematic review.

Nurses are vital in identifying and preventive pressure injuries (PIs) in hospitalized patients undergoing open heart surgery. Interventions to prevent PIs are crucial for every critical patient, and it's essential to recognize that preventing PIs involves a complex intervention. To examine the nursing interventions for the prevention of PI in patients with open heart surgery. A systematic review study. Web of Science, Science Direct, PubMed, Scopus, MEDLINE Ultimate, CINAHL Ultimate, ULAKBIM, Cochrane Library, Google Scholar and university library databases were scanned. The initial search performed in the databases was updated on 4 February 2023, and on 7 April 2024, for potential publications included in that period. Data between February 2013 and April 2024 were scanned. The databases were searched with the keywords 'pressure injury', 'nursing interventions' and 'open heart surgery'. The systematic compilation process was carried out in accordance with the guidelines in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide. Seventeen studies were examined using nursing interventions that applied to the selected study population. Care packages included an inflatable head pad, a pressure sensor mattress cover, multi-layer silicone foam, pressure-reducing coatings, endotracheal tube (ETT) repositioning and cuff pressure regulation. Interventions to reduce PI in open heart surgery patients are applied in the preadmission, perioperative and postoperative periods. It was concluded that care packages, inflatable head pads, pressure sensor bedspreads, multi-layered silicone foam, pressure-reducing covers, ETT repositioning and cuff pressure regulation were effective in all nursing interventions. The strength of the available evidence was rated from strong to weak. These findings reveal an efficient combination of multi-component nursing interventions for preventing PIs in planning patient care in the intensive care. The interventions that are used throughout the patient's entire care process are crucial for the prevention of PIs.

Examination of role of the AMP-activated protein kinase (Ampk) signaling pathway during low salinity adaptation in the mud crab, Scylla paramamosain, with reference to glucolipid metabolism

It is known that the marine euryhaline crab, mud crab (Scylla paramamosain), is capable of adapting to low salinity conditions through an innate osmoregulatory system. However, the influence of nutritional conditions during low salinity adaptation has not been fully elucidated. In this study, transcriptome analysis was employed to examine whether low salinity affects the AMP-activated protein kinase (Ampk) signaling pathway, and thereby carbohydrate and lipid metabolism. Further analysis revealed that low salinity activated the expression of P-Ampk and promoted glycolysis and lipolysis, which enhances glycogen and lipid utilization. Nutritional deprivation confirmed that nutrients influenced the survival and osmotic pressure regulation of mud crab under to low salinity via the Ampk signaling pathway. During adaptation to low salinity, carbohydrates were the primary energy source in the initial 7 days, followed by lipids. Further investigation showed that pharmacological stimulation of mechanistic targets in the Ampk signaling pathway using metformin could promote the osmotic pressure regulation of mud crab, confirmed the pivotal role of this pathway in low salinity adaptation. Overall, the present study demonstrated that nutrition, metabolism and osmotic pressure regulation interactively contribute to salinity adaptation in mud crab. Specifically, low salinity induced remodeling of nutritional metabolism homeostasis and promoted glycolipid catabolism, thereby providing energy for osmotic pressure regulation in mud crabs.

Renal denervation: a key approach to hypertension and cardiovascular disease.

Sympathetic activation plays a critical role in the development of hypertension and cardiovascular disease, including heart failure and arrhythmias. Renal nerves contribute to the regulation of blood pressure and fluid volume through renal sympathetic efferent nerves, and to the modulation of sympathetic outflow through renal sensory afferent nerves. Previous studies including ours suggest that selective afferent renal denervation with preservation of efferent renal nerves can significantly decrease central sympathetic outflow in animal models of hypertension with renal damage. In Dahl salt-sensitive rats fed high salt diet from an early age, a model of hypertensive heart failure, this central sympathoinhibition by afferent renal denervation may attenuate the development of heart failure without significant blood pressure reduction. Accumulating clinical evidence supports the efficacy of renal denervation as an antihypertensive treatment. However, it remains important to clarify the appropriate indications and predictors of responders to renal denervation in the treatment of hypertension. Several clinical studies suggest beneficial effects of renal denervation in patients with heart disease, with or without hypertension, although most were not sham-controlled. In particular, some clinical studies have demonstrated that renal denervation reduces the incidence of atrial fibrillation or cardiovascular events even without a significant antihypertensive effect. It is essential to accumulate more insightful data in patients undergoing renal denervation, to establish the efficacy of renal denervation in patients with cardiovascular disease in the clinical setting, and to elucidate the therapeutic mechanisms of renal denervation and the renal nerves-linked pathophysiology of cardiovascular disease in basic research. This review outlines the effects of renal denervation on sympathetic activity and organ damage in animal models of hypertension and hypertensive heart failure, including our own data. Beyond the antihypertensive effects, the beneficial effects of renal denervation on cardiovascular disease are also discussed based on clinical studies. Several animal and clinical studies suggest the cardioprotective effects of renal denervation even in the absence of significant blood pressure reduction, probably due to its sympathoinhibitory effects.

G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets.

G protein-coupled receptors (GPCRs) mediate cellular responses to a myriad of hormones and neurotransmitters that play vital roles in the regulation of physiological processes such as blood pressure. In organs such as the artery and kidney, hormones or neurotransmitters, such as angiotensin II (Ang II), dopamine, epinephrine, and norepinephrine exert their functions via their receptors, with the ultimate effect of keeping normal vascular reactivity, normal body sodium, and normal blood pressure. GPCR kinases (GRKs) exert their biological functions, by mediating the regulation of agonist-occupied GPCRs, non-GPCRs, or non-receptor substrates. In particular, increasing number of studies show that aberrant expression and activity of GRKs in the cardiovascular system and kidney inhibit or stimulate GPCRs (e.g., dopamine receptors, Ang II receptors, and α- and β-adrenergic receptors), resulting in hypertension. Current studies focus on the effect of selective GRK inhibitors in cardiovascular diseases, including hypertension. Moreover, genetic studies show that GRK gene variants are associated with essential hypertension, blood pressure response to antihypertensive medicines, and adverse cardiovascular outcomes of antihypertensive treatment. In this review, we present a comprehensive overview of GRK-mediated regulation of blood pressure, role of GRKs in the pathogenesis of hypertension, and highlight potential strategies for the treatment of hypertension. Schematic representation of GPCR desensitization process. Activation of GPCRs begins with the binding of an agonist to its corresponding receptor. Then G proteins activate downstream effectors that are mediated by various signaling pathways. GPCR signaling is halted by GRK-mediated receptor phosphorylation, which causes receptor internalization through β-arrestin.

Cardiomyocyte PANX1 Controls Glycolysis and Neutrophil Recruitment in Hypertrophy.

PANX1 (pannexin 1), a ubiquitously expressed ATP release membrane channel, has been shown to play a role in inflammation, blood pressure regulation, and myocardial infarction. However, the possible role of PANX1 in cardiomyocytes in the progression of heart failure has not yet been investigated. We generated a novel mouse line with constitutive deletion of PANX1 in cardiomyocytes (Panx1MyHC6). PANX1 deletion in cardiomyocytes had no effect on unstressed heart function but increased the glycolytic metabolism and resulting glycolytic ATP production, with a concurrent decrease in oxidative phosphorylation, both in vivo and in vitro. In vitro, treatment of H9c2 cardiomyocytes with isoproterenol led to PANX1-dependent release of ATP and Yo-Pro-1 uptake, as assessed by pharmacological blockade with spironolactone and siRNA-mediated knockdown of PANX1. To investigate nonischemic heart failure and the preceding cardiac hypertrophy, we administered isoproterenol, and we demonstrated that Panx1MyHC6 mice were protected from systolic and diastolic left ventricle volume increases as a result of cardiomyocyte hypertrophy. Moreover, we found that Panx1MyHC6 mice showed decreased isoproterenol-induced recruitment of immune cells (CD45+), particularly neutrophils (CD11b+, Ly6g+), to the myocardium. Together, these data demonstrate that PANX1 deficiency in cardiomyocytes increases glycolytic metabolism and protects against cardiac hypertrophy in nonischemic heart failure at least in part by reducing immune cell recruitment. Our study implies PANX1 channel inhibition as a therapeutic approach to ameliorate cardiac dysfunction in patients with heart failure.

Shear wave elastography of transverse carpal ligament increased with simulated carpal tunnel pressure

BackgroundElevation of carpal tunnel pressure is known to be associated with carpal tunnel syndrome. This study aimed to correlate the shear wave elastography in the transverse carpal ligament (TCL) with carpal tunnel pressures using a cadaveric model.MethodsEight human cadaveric hands were dissected to evacuate the tunnels. A medical balloon was inserted into each tunnel and connected to a pressure regulator to simulate tunnel pressure in the range of 0-210 mmHg with an increment of 30 mmHg. Shear wave velocity and modulus was measure in the middle of TCL.ResultsSWV and SWE were significantly dependent on the pressure levels (p < 0.001), and positively correlated to the tunnel pressure (SWV: R = 0.997, p < 0.001; SWE: R = 0.996, p < 0.001). Regression analyses showed linear relationship SWV and pressure (SWV = 4.359 + 0.0263 * Pressure, R2 = 0.994) and between SWE and pressure (SWE = 48.927 + 1.248 * Pressure, R2 = 0.996).ConclusionThe study indicated that SWV and SWE in the TCL increased linearly as the tunnel pressure increased within the current pressure range. The findings suggested that SWV/SWE in the TCL has the potential for prediction of tunnel pressure and diagnosis of carpal tunnel syndrome.