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Shock (Augusta, Ga.) May 2024Sepsis causes dysfunction in different organs, but the pathophysiological mechanisms behind it are similar and mainly involve complex haemodynamic and cellular...
Sepsis causes dysfunction in different organs, but the pathophysiological mechanisms behind it are similar and mainly involve complex haemodynamic and cellular dysfunction. The importance of microcirculatory dysfunction in sepsis is becoming increasingly evident, in which endothelial dysfunction and glycocalyx degradation play a major role. This study aimed to investigate the effects of hydrogen-rich saline (HRS) on renal microcirculation in septic renal failure, and whether Sirt1 was involved in the renoprotective effects of HRS. Rats model of sepsis was established by cecal ligation and puncture, and septic rats were intraperitoneal injected with HRS (10 ml/kg). We found that in sepsis, the degree of glycocalyx shedding was directly proportional to the severity of sepsis. The seven-day survival rate of rats in the HRS + CLP group (70%) was higher than that of the CLP group (30%). HRS improved acidosis and renal function and reduced the release of inflammatory factors (TNF, IL-1βand IL-6). The endothelial glycocalyx of capillaries in the HRS + CLP group (115 nm) was observed to be significantly thicker than that in the CLP group (44 nm) and EX527 (67.2 nm) groups by electron microscopy, and fewer glycocalyx metabolites (SDC-1, HS, HA, and MMP9) were found in the blood. Compared with the CLP group, HRS reduced renal apoptosis and upregulated Sirt1 expression, and inhibited the NF-κB/MMP9 signalling pathway. In addition, HRS did not damage immune function in septic rats as well. Generally speaking, our results suggest that HRS can alleviate the inflammatory response, inhibit glycocalyx shedding, improve septic kidney injury, and enhance survival rate.
PubMed: 38888497
DOI: 10.1097/SHK.0000000000002404 -
Frontiers in Cardiovascular Medicine 2024Microvascular resistance reserve (MRR) is a recently introduced specific index of coronary microcirculation. MRR calculation can utilize parameters deriving from...
BACKGROUND
Microvascular resistance reserve (MRR) is a recently introduced specific index of coronary microcirculation. MRR calculation can utilize parameters deriving from coronary flow reserve (CFR) assessment, provided that intracoronary pressure data are also available. The previously proposed pressure-bounded CFR (CFRpb) defines the possible CFR interval on the basis of resting and hyperemic pressure gradients in the epicardial vessel, however, its correlation to the Doppler wire measurement was reported to be rather poor without the correction for hydrostatic pressure.
PURPOSE
We aimed to determine the pressure-bounded coronary MRR interval with hydrostatic pressure correction according to the previously established equations of CFRpb adapted for the MRR concept. Furthermore, we also aimed to design a prediction model using the actual MRR value within the pressure-bounded interval and validate the results against the gold-standard Doppler wire technique.
METHODS
Hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. In the derivation cohort the pressure-bounded MRR interval (between MRRpb and MRRpb) was determined solely from hydrostatic pressure-corrected intracoronary pressure data. The actual MRR was calculated by simple hemodynamic equations incorporating the anatomical data of the three-dimensionally reconstructed coronary artery (MRR). These results were analyzed by regression analyses to find relations between the MRRpb bounds and the actual MRR.
RESULTS
In the derivation cohort of 23 measurements, linear regression analysis showed a tight relation between MRRpb and MRR ( = 0.74, < 0.0001). Using this relation (MRR = 1.04 + 0.51 × MRRpb), the linear prediction of the MRR was tested in the validation cohort of 19 measurements against the gold standard Doppler wire technique. A significant correlation was found between the linearly predicted and the measured values ( = 0.54, = 0.01). If the area stenosis (AS%) was included to a quadratic prediction model, the correlation was improved ( = 0.63, = 0.004).
CONCLUSIONS
The MRR can be predicted reliably to assess microvascular function by our simple model. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement provides a simultaneous physiological assessment of the macro- and microvasculature.
PubMed: 38887446
DOI: 10.3389/fcvm.2024.1322161 -
Abdominal Radiology (New York) Jun 2024Contrast-enhanced ultrasound (CEUS) is an advanced ultrasound (US) technique utilizing ultrasound contrast agents (UCAs) to provide detailed visualization of anatomic... (Review)
Review
Contrast-enhanced ultrasound (CEUS) is an advanced ultrasound (US) technique utilizing ultrasound contrast agents (UCAs) to provide detailed visualization of anatomic and vascular architecture, including the depiction of microcirculation. CEUS has been well-established in echocardiography and imaging of focal hepatic lesions and recent studies have also shown the utility of CEUS in non-hepatic applications like the urinary system. The updated guidelines by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) from 2018 describe the use of CEUS for non-hepatic applications. CEUS' excellent safety profile and spatial resolution make it a superior modality to conventional US and is often comparable and even superior to CECT in some instances. In comparison to other cross-sectional imaging modalities such as CECT or MRI, CEUS offers a safe (by virtue of non-nephrotoxic US contrast agents), accurate, cost-efficient, readily available, and a quick means of evaluation of multiple pathologies of the urinary system. CEUS also has the potential to reduce the overall economic burden on patients requiring long-term follow-up due to its low cost as compared to CT or MRI techniques. This comprehensive review focuses on the applications of CEUS in evaluating the urinary system from the kidneys to the urinary bladder. CEUS can be utilized in the kidney to evaluate complex cystic lesions, indeterminate lesions, pseudotumors (vs solid renal tumors), renal infections, and renal ischemic disorders. Additionally, CEUS has also been utilized in evaluating renal transplants. In the urinary bladder, CEUS is extremely useful in differentiating a bladder hematoma and bladder cancer when conventional US techniques show equivocal results. Quantitative parameters of time-intensity curves (TICs) of CEUS examinations have also been studied to stage and grade bladder cancers. Although promising, further research is needed to definitively stage bladder cancers and classify them as muscle-invasive or non-muscle invasive using quantitative CEUS to guide appropriate intervention. CEUS has been very effective in the classification of cystic renal lesions, however, further research is needed in differentiating benign from malignant renal masses.
PubMed: 38884782
DOI: 10.1007/s00261-024-04388-4 -
Plastic and Reconstructive Surgery.... Jun 2024Raynaud disease of the hands is a complex disorder resulting in inappropriate constriction and/or insufficient dilation in microcirculation. There is an emerging role...
BACKGROUND
Raynaud disease of the hands is a complex disorder resulting in inappropriate constriction and/or insufficient dilation in microcirculation. There is an emerging role for botulinum toxin type A (BTX-A) in the treatment armamentarium for refractory Raynaud disease. The aim of this systematic review was to critically evaluate the management of primary and secondary Raynaud disease treated with BTX-A intervention.
METHODS
We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of clinical studies assessing treatment of primary or secondary Raynaud disease with BTX-A by searching Ovid MEDLINE and Embase databases from inception to first August 2023. The review protocol was prospectively registered on the PROSPERO database (CRD42022312253).
RESULTS
Our search strategy identified 288 research articles, of which 18 studies [four randomized controlled trials (RCTs), two non-RCTs, five case series, and seven retrospective cohort studies] were eligible for analysis. Meta-analysis demonstrated that the probability of pain visual analog scale score improvement with BTX-A intervention was 81.95% [95% confidence interval (74.12-87.81) = 0.19, heterogeneity = 26%] and probability of digital ulcer healing was 79.37% [95% confidence interval (62.45-89.9) = 0.02, heterogeneity = 56%].
CONCLUSIONS
Delivery of BTX-A to digital vessels in the hand may be an effective management strategy for primary and secondary Raynaud disease. A definitive, appropriately-powered RCT with objective functional and patient-reported outcome measures is required to accurately assess and quantify the efficacy of BTX-A in Raynaud disease of the hands.
PubMed: 38881966
DOI: 10.1097/GOX.0000000000005885 -
Journal of Bodywork and Movement... Jul 2024In this case report a new approach called neurofascialvascular training (NFVT) is described. NFVT consists of two mechanisms which improve mechanosensitivity in carpal...
INTRODUCTION
In this case report a new approach called neurofascialvascular training (NFVT) is described. NFVT consists of two mechanisms which improve mechanosensitivity in carpal tunnel syndrome (CTS). The first involves increased blood flow in the nerve microcirculation, while the second stimulates the reciprocal sliding between the thin sheets of connective tissue inside the nerve. The goal of these two actions is to squeeze, mobilize and reduce intraneural edema. The novelty of this approach is the simultaneous involvement of multiple physiological systems to reduce nerve mechanosensitivity. This case report describes the rehabilitation progress achieved by NFVT in a patient with CTS.
MAIN SYMPTOMS AND/OR IMPORTANT CLINICAL FINDINGS
A 64-year-old woman complaining of nocturnal pain and tingling with severe impairment of sleep quality for two years was diagnosed at CTS.
THERAPEUTIC INTERVENTIONS
The patient underwent nine 30-min exercise sessions of NFVT.
OUTCOMES
At each session and at the last follow-up 3 months after the end of treatment the following tests were performed: the upper limb neurodynamic test1 (ULNT1), the Hand Grip Meter and the Phdurkan test. Furthermore ultrasound, numerical rating scale and the Boston Carpal Tunnel Questionnaire (BCTQ) were also adopted.
CONCLUSION
NFVT can improve symptoms and motor dysfunction in a patient with CTS.
TAKE-AWAY LESSON
In the presence of mild carpal tunnel syndrome, active neurofascialvascular training that increases peripheral blood flow and targets fascial tissue within the peripheral nervous system can resolve symptoms and produce significant improvement within a few months of starting treatment.
Topics: Humans; Carpal Tunnel Syndrome; Female; Middle Aged; Exercise Therapy; Hand Strength
PubMed: 38876659
DOI: 10.1016/j.jbmt.2023.10.003 -
The Journal of Infectious Diseases Jun 2024A hallmark of cerebral malaria is sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain microcirculation. Antibodies contribute to malaria...
A hallmark of cerebral malaria is sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain microcirculation. Antibodies contribute to malaria immunity, but it remains unclear whether functional antibodies targeting parasite-expressed ligand can block cytoadhesion in the brain. Here, we screened the plasma of older children and young adults in Malawi to characterize the antibody response against the P. falciparum-IE surface and used a bioengineered 3D human brain microvessel model incorporating variable flow dynamics to measure adhesion blocking responses. We found a strong correlation between surface antibody reactivity by flow cytometry and reduced P. falciparum-IE binding in 3D microvessels. Moreover, there was a threshold of surface antibody reactivity necessary to achieve robust inhibitory activity. Our findings provide evidence of the acquisition of adhesion blocking antibodies against cerebral binding variants in people exposed to stable P. falciparum transmission and suggest the quality of the inhibitory response can be influenced by flow dynamics.
PubMed: 38875153
DOI: 10.1093/infdis/jiae315 -
American Journal of Physiology. Heart... Jun 2024
PubMed: 38874617
DOI: 10.1152/ajpheart.00390.2024 -
Antioxidants & Redox Signaling Jun 2024Mitochondrial dynamics in alveolar macrophages (AMs) are associated with sepsis-induced acute lung injury (ALI). In this study, we aimed to investigate whether changes...
AIMS
Mitochondrial dynamics in alveolar macrophages (AMs) are associated with sepsis-induced acute lung injury (ALI). In this study, we aimed to investigate whether changes in mitochondrial dynamics could alter the polarization of AMs in sepsis-induced ALI and to explore the regulatory mechanism of mitochondrial dynamics by focusing on SIRT3-induced optic atrophy protein 1 (OPA1) deacetylation.
RESULTS
The AMs of sepsis-induced ALI showed imbalanced mitochondrial dynamics and polarization to the M1 macrophage phenotype. In sepsis, SIRT3 overexpression promotes mitochondrial dynamic equilibrium in AMs. However, 3TYP-specific inhibition of SIRT3 increased the mitochondrial dynamic imbalance and pro-inflammatory polarization of AMs and further aggravated sepsis-induced ALI. OPA1 is directly bound to and deacetylated by SIRT3 in AMs. In AMs of sepsis-induced ALI, SIRT3 protein expression was decreased and OPA1 acetylation was increased. OPA1 acetylation at the lysine 792 amino acid residue (OPA1-K792) promotes self-cleavage and is associated with an imbalance in mitochondrial dynamics. However, decreased acetylation of OPA1-K792 reversed the pro-inflammatory polarization of AMs and protected the barrier function of alveolar epithelial cells in sepsis-induced ALI.
INNOVATION
Our study revealed for the first time the regulation of mitochondrial dynamics and AMs polarization by SIRT3-mediated deacetylation of OPA1 in sepsis-induced ALI, which may serve as an intervention target for precision therapy of the disease.
CONCLUSIONS
Our data suggest that imbalanced mitochondrial dynamics promote pro-inflammatory polarization of AMs in sepsis-induced ALI, and that deacetylation of OPA1 mediated by SIRT3 improves mitochondrial dynamic equilibrium, thereby ameliorating lung injury.
PubMed: 38874521
DOI: 10.1089/ars.2023.0322 -
British Journal of Pharmacology Jun 2024Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can...
BACKGROUND AND PURPOSE
Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can initiate the plasma kallikrein-kinin cascade, producing inflammation and angioedema. The role of Factor XII in psoriasis is unknown.
EXPERIMENTAL APPROACH
The effects of deficiency of Factor XII or its enzymatic substrate, prekallikrein, were examined in the imiquimod-induced mouse model of psoriasis. Skin microcirculation was assessed using intravital confocal microscopy and laser Doppler flowmeter. A novel antibody blocking Factor XII activation was evaluated for psoriasis prevention.
KEY RESULTS
Expression of Factor XII was markedly up-regulated in human and mouse psoriatic skin. Genetic deletion of Factor XII or prekallikrein, attenuated imiquimod-induced psoriatic lesions in mice. Psoriatic induction increased skin microvascular blood perfusion, causing vasodilation, hyperpermeability and angiogenesis. It also promoted neutrophil-vascular interaction, inflammatory cytokine release and enhanced Factor XII / prekallikrein enzymatic activity with elevated bradykinin. Factor XII or prekallikrein deficiency ameliorated these microvascular abnormalities and abolished bradykinin increase. Antagonism of bradykinin B receptors reproduced the microvascular protection of Factor XII / prekallikrein deficiency, attenuated psoriatic lesions, and prevented protection by Factor XII / prekallikrein deficiency against psoriasis. Furthermore, treatment of mice with Factor XII antibody alleviated experimentally induced psoriasis and suppressed microvascular inflammation.
CONCLUSION AND IMPLICATIONS
Activation of Factor XII promoted psoriasis via prekallikrein-dependent formation of bradykinin, which critically mediated psoriatic microvascular inflammation. Inhibition of contact activation represents a novel therapeutic strategy for psoriasis.
PubMed: 38872396
DOI: 10.1111/bph.16428 -
Nature Communications Jun 2024In acute ischemic stroke, even when successful recanalization is obtained, downstream microcirculation may still be obstructed by microvascular thrombosis, which is...
In acute ischemic stroke, even when successful recanalization is obtained, downstream microcirculation may still be obstructed by microvascular thrombosis, which is associated with compromised brain reperfusion and cognitive decline. Identifying these microthrombi through non-invasive methods remains challenging. We developed the PHySIOMIC (Polydopamine Hybridized Self-assembled Iron Oxide Mussel Inspired Clusters), a MRI-based contrast agent that unmasks these microthrombi. In a mouse model of thromboembolic ischemic stroke, our findings demonstrate that the PHySIOMIC generate a distinct hypointense signal on T*-weighted MRI in the presence of microthrombi, that correlates with the lesion areas observed 24 hours post-stroke. Our microfluidic studies reveal the role of fibrinogen in the protein corona for the thrombosis targeting properties. Finally, we observe the biodegradation and biocompatibility of these particles. This work demonstrates that the PHySIOMIC particles offer an innovative and valuable tool for non-invasive in vivo diagnosis and monitoring of microthrombi, using MRI during ischemic stroke.
Topics: Animals; Polymers; Magnetic Resonance Imaging; Indoles; Mice; Contrast Media; Ferric Compounds; Disease Models, Animal; Thrombosis; Male; Stroke; Humans; Fibrinogen; Ischemic Stroke; Mice, Inbred C57BL; Protein Corona; Brain
PubMed: 38871729
DOI: 10.1038/s41467-024-49480-x