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PloS One 2024Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI,... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI, renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulation, which may offer mechanistic insight into the pathophysiology of septic AKI. The aim of the current study is to investigate the effects of vasopressin and angiotensin II on renal microcirculatory perfusion in a cohort of patients with septic shock.
METHODS AND ANALYSIS
In this single centre, mechanistically focussed, randomised controlled study, 45 patients with septic shock will be randomly allocated to either of the study vasopressors (vasopressin or angiotensin II) or standard therapy (norepinephrine). Infusions will be titrated to maintain a mean arterial pressure (MAP) target set by the attending clinician. Renal microcirculatory assessment will be performed for the cortex and medulla using contrast-enhanced ultrasound (CEUS) and urinary oxygen tension (pO2), respectively. Renal macrovascular flow will be assessed via renal artery ultrasound. Measurement of systemic macrovascular flow will be performed through transthoracic echocardiography (TTE) and microvascular flow via sublingual incident dark field (IDF) video microscopy. Measures will be taken at baseline, +1 and +24hrs following infusion of the study drug commencing. Blood and urine samples will also be collected at the measurement time points. Longitudinal data will be compared between groups and over time.
DISCUSSION
Vasopressors are integral to the management of patients with septic shock. This study aims to further understanding of the relationship between this therapy, renal perfusion and the development of AKI. In addition, using CEUS and urinary pO2, we hope to build a more complete picture of renal perfusion in septic shock by interrogation of the constituent parts of the kidney. Results will be published in peer-reviewed journals and presented at academic meetings.
TRIAL REGISTRATION
The REPERFUSE study was registered on Clinical Trials.gov (NCT06234592) on the 30th Jan 24.
Topics: Humans; Shock, Septic; Vasoconstrictor Agents; Microcirculation; Acute Kidney Injury; Kidney; Vasopressins; Angiotensin II; Male; Female; Norepinephrine; Renal Circulation; Middle Aged; Adult
PubMed: 38870103
DOI: 10.1371/journal.pone.0304227 -
JACC. Cardiovascular Interventions Jun 2024
Topics: Humans; Coronary Circulation; Microcirculation; Heart Failure; Coronary Artery Disease; Coronary Vessels; Risk Factors
PubMed: 38866463
DOI: 10.1016/j.jcin.2024.04.041 -
JACC. Cardiovascular Interventions Jun 2024
Topics: Humans; Coronary Circulation; Microcirculation; Heart Failure; Coronary Artery Disease; Risk Factors; Coronary Vessels; Prognosis
PubMed: 38866462
DOI: 10.1016/j.jcin.2024.04.032 -
Clinics in Shoulder and Elbow Jun 2024Little is known about alterations of the rotator cuff (RC) macroscopic vasculature associated with medical conditions and/or habits that predispose a person to diseases...
BACKGROUND
Little is known about alterations of the rotator cuff (RC) macroscopic vasculature associated with medical conditions and/or habits that predispose a person to diseases of the peripheral microcirculation. The high frequency of cuff tear and re-tear in patients with diabetes, hypercholesterolemia, uncontrolled arterial hypertension, or metabolic syndrome may be due to tissue hypovascularity.
METHODS
The macroscopic vasculature of both the articular and bursal sides of the posterosuperior RC was evaluated arthroscopically in 107 patients (mean age, 58.2 years) with no RC tear. Patients were divided into three groups according to medical comorbidities and lifestyle factors (group I, none; group II, smokers and/or drinkers and one comorbidity; and group III, two or more comorbidities). Pulsating vessels originating from both the myotendinous and osteotendinous junctions were assessed as "clearly evident," "poorly evident," or "not evident."
RESULTS
Groups I, II, and III comprised 36, 45, and 26 patients, respectively. Within the myotendinous junction, vessels were visualized in 22 group I patients (61%), 25 group II patients (55%), and 6 group III patients (23%) (P=0.007). Pulsating arterial vessels originating from the osteotendinous junction were seen in 42%, 36%, and 0% of patients, respectively (P<0.001). Within the bursal side of the RC, a dense anastomotic network was visualized (either clearly or poorly) in 94% (34), 80% (36), and 35% (9) of patients, respectively (P<0.001).
CONCLUSIONS
The macroscopic vasculature of the RC is influenced by pre-existing diseases and lifestyle factors, which may impair peripheral microcirculation. Level of evidence: III.
PubMed: 38863404
DOI: 10.5397/cise.2024.00066 -
The World Journal of Men's Health May 2024Physiological aging is associated with microvascular dysfunction, including in the penis, and this may contribute to age-related erectile dysfunction (ED). Low-intensity...
Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction.
PURPOSE
Physiological aging is associated with microvascular dysfunction, including in the penis, and this may contribute to age-related erectile dysfunction (ED). Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a non-invasive intervention for ED, but its effect on penile microvascular function, remains unclear. Our objectives are to (i) evaluate the effect of Li-ESWT (specifically radial type ESWT [rESWT]) on penile microvascular perfusion (PMP) in aging rats, (ii) elucidate a possible mechanism, and (iii) evaluate its impact on angiogenic and smooth muscle biomarkers in cavernosal tissue.
MATERIALS AND METHODS
Male rats (n=9; 15-18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. Rats were euthanized at the end of the study and penile tissues were analyzed for angiogenic markers (vascular endothelial growth factor-A [VEGF-A], endothelial nitric oxide synthase [eNOS]) and smooth muscle content (α-actin) using immunostaining, Western blot, and quantitative polymerase chain reaction (qPCR).
RESULTS
rESWT resulted in more than a 2-fold increase in PMP (from 68.5 arbitrary units; 163.7 AU). L-NAME injection produced a <40%-50% decrease (185.3 to 101.0 AU) in rESWT-induced PMP response. Immunostaining revealed increased α-actin, eNOS, and VEGF-A in the cavernosum and these findings were confirmed by qPCR and Western blot results.
CONCLUSIONS
rESWT improved PMP, which may be mediated increased VEGF expression, which stimulates the NO/cyclic guanosine monophosphate pathway, resulting in sustained PMP. rESWT devices could offer a safe, non-invasive treatment for age-related ED.
PubMed: 38863376
DOI: 10.5534/wjmh.240032 -
Science Progress 2024Pericytes (PCs) are versatile cells integral to the microcirculation wall, exhibiting specific stem cell traits. They are essential in modulating blood flow, ensuring... (Review)
Review
Pericytes (PCs) are versatile cells integral to the microcirculation wall, exhibiting specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, maintaining homeostasis, and aiding tissue repair process. Given their involvement in numerous disease-related pathological and physiological processes, the regulation of PCs has emerged as a focal point of research. Adenomyosis is characterized by the presence of active endometrial glands and stroma encased by an enlarged and proliferative myometrial layer, further accompanied by fibrosis and new blood vessel formation. This distinct pathological condition might be intricately linked with PCs. This article comprehensively reviews the markers associated with PCs, their contributions to angiogenesis, blood flow modulation, and fibrotic processes. Moreover, it provides a comprehensive overview of the current research on adenomyosis pathophysiology, emphasizing the potential correlation and future implications regarding PCs and the development of adenomyosis.
Topics: Adenomyosis; Pericytes; Humans; Female; Neovascularization, Pathologic; Animals; Fibrosis; Endometrium; Myometrium; Biomarkers
PubMed: 38863331
DOI: 10.1177/00368504241257126 -
Human Immunology Jun 2024Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by the production of galactose‑deficient IgA1 (Gd‑IgA1) and the deposition of immune...
BACKGROUND
Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by the production of galactose‑deficient IgA1 (Gd‑IgA1) and the deposition of immune complexes in the kidney. Exploring the landscape of immune dysregulation in IgAN is valuable for pathogenesis and disease treatment. We conducted Mendelian randomization (MR) to assess the causal correlations between inflammation and IgAN.
METHODS
Based on available genetic datasets, we investigated potential causal links between inflammation and the risk of IgAN using two-sample MR. We used genome-wide association study (GWAS) summary statistics of 5 typical inflammation markers, 41 inflammatory cytokines, and 731 immune cell signatures, accessed from the public GWAS Catalog. The primary method employed for MR analysis was Inverse Variance Weighted (IVW). To confirm consistency across results, four supplementary MR methods were also conducted: MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. To assess pleiotropy, we used the MR-Egger regression intercept test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Cochrane's Q statistic was applied to evaluate heterogeneity. Additionally, the stability of the MR findings was verified through the leave-one-out sensitivity analysis.
RESULTS
This study revealed that interleukin-7 (IL-7) and stem cell growth factor beta (SCGF-β) were possibly associated with the risk of IgAN according to the IVW approach, with estimated odds ratios (OR) of 1.059 (95 % confidence interval [CI] 1.015 to 1.104, P = 0.008) and 1.043 (95 % CI 1.002 to 1.085, P = 0.037). Five immune traits were identified that might be linked to IgAN risk, each with P-values below 0.01, including natural killer T %T cell (OR = 1.058, 95 % CI: 1.020 to 1.097, P = 0.002), natural killer T %lymphocyte (OR = 1.055, 95 % CI: 1.016 to 1.096, P = 0.006), CD25 CD8 T cell %T cell (OR = 1.057, 95 % CI: 1.016 to 1.099, P = 0.006), CD3 on effector memory CD4 T cell (OR = 1.045, 95 % CI: 1.019 to 1.071, P = 0.001), and CD3 on CD28 CD45RA CD8 T cell (OR = 1.042, 95 % CI: 1.016 to 1.068, P = 0.001). CD4 on central memory CD4 T cell might be a protective factor for IgAN (OR = 0.922, 95 % CI: 0.875 to 0.971, P = 0.002). Moreover, IgAN may be implicated in a high risk of elevated granulocyte colony-stimulating factor (G-CSF) (OR = 1.114, 95 % CI 1.002 to 1.239, P = 0.046).
CONCLUSION
Our study revealed exposures among typical inflammation markers, inflammatory cytokines, and immune cell signatures that may potentially linked to IgAN risk by MR analysis. This insight may advance our understanding of the etiology of IgAN and support the development of targeted therapeutic strategies.
PubMed: 38861759
DOI: 10.1016/j.humimm.2024.110830 -
Wounds : a Compendium of Clinical... May 2024Full-thickness skin defects often are managed with split-thickness skin grafting. The wound healing process, including formation of new vessels during the healing of...
BACKGROUND
Full-thickness skin defects often are managed with split-thickness skin grafting. The wound healing process, including formation of new vessels during the healing of skin grafts, is complex.
OBJECTIVE
To evaluate the microcirculatory changes in the treated tissue after skin grafting to analyze perfusion dynamics during the wound healing process.
MATERIALS AND METHODS
Fourteen full-thickness skin defects were created on the back of 14 adult male Lewis rats. All wounds were treated with autologous split-thickness skin grafts. The perfusion dynamics were assessed for 84 days with an O2C device that combines a laser light to determine blood flow and white light to determine postcapillary SO2 and the rHb.
RESULTS
Blood flow increased for 50 days after grafting. SO2 decreased in superficial skin layers (depth of 2 mm) and increased in deep skin layers (depth of 8 mm) during the entire observation period. The rHb increased until day 10 in superficial layers and until day 20 in deep tissue layers.
CONCLUSION
The microcirculatory changes reflect the different phases of wound healing. Long after the skin transplants were macroscopically healed, alterations in microcirculation were still detected. These alterations were caused by the long-lasting changes in tissue metabolism due to the formation, conversion, and degradation of the dermal matrix and vessels during wound healing and scar formation.
Topics: Animals; Wound Healing; Microcirculation; Skin Transplantation; Rats; Male; Rats, Inbred Lew; Skin; Disease Models, Animal
PubMed: 38861214
DOI: 10.25270/wnds/23112 -
Scientific Reports Jun 2024
PubMed: 38858541
DOI: 10.1038/s41598-024-64285-0 -
Biochimie Jun 2024Uropathogenic strains of E. coli (UPEC) is a leading cause of sepsis, deploying multiple virulence factors to evade host immune responses. Notably, alpha-hemolysin...
Uropathogenic strains of E. coli (UPEC) is a leading cause of sepsis, deploying multiple virulence factors to evade host immune responses. Notably, alpha-hemolysin (HlyA) produced by UPEC is implicated in septic symptoms associated with bacteremia, correlating with thrombocytopenia, a critical indicator of organ dysfunction and a predictor of poorer patient prognosis. This study meticulously explores the impact of sublytic concentrations of HlyA on platelets. Findings reveal that HlyA triggers an increase in intracellular calcium, activating calpain and exposing phosphatidylserine to the cell surface, as validated by flow cytometric experiments. Electron microscopy reveals a distinctive balloon-like shape in HlyA-treated platelets, indicative of a procoagulant state. The toxin induces the release of procoagulant extracellular vesicles and the secretion of alpha and dense granules. Overall, the results point to HlyA inducing a necrotic-like procoagulant state in platelets. The effects of sublytic concentrations of HlyA on both erythrocytes and platelets could have a potential impact on capillary microcirculation. Targeting HlyA emerges as a viable therapeutic strategy to mitigate the adverse effects of UPEC infections, especially in South American countries where these infections are endemic, underscoring its significance as a potential therapeutic target.
PubMed: 38857695
DOI: 10.1016/j.biochi.2024.06.001