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International Journal of Molecular... May 2024Endothelial cells (ECs) line the inner surface of all blood vessels and form a barrier that facilitates the controlled transfer of nutrients and oxygen from the... (Review)
Review
Endothelial cells (ECs) line the inner surface of all blood vessels and form a barrier that facilitates the controlled transfer of nutrients and oxygen from the circulatory system to surrounding tissues. Exposed to both laminar and turbulent blood flow, ECs are continuously subject to differential mechanical stimulation. It has been well established that the shear stress associated with laminar flow (LF) is atheroprotective, while shear stress in areas with turbulent flow (TF) correlates with EC dysfunction. Moreover, ECs show metabolic adaptions to physiological changes, such as metabolic shifts from quiescence to a proliferative state during angiogenesis. The AMP-activated protein kinase (AMPK) is at the center of these phenomena. AMPK has a central role as a metabolic sensor in several cell types. Moreover, in ECs, AMPK is mechanosensitive, linking mechanosensation with metabolic adaptions. Finally, recent studies indicate that AMPK dysregulation is at the center of cardiovascular disease (CVD) and that pharmacological targeting of AMPK is a promising and novel strategy to treat CVDs such as atherosclerosis or ischemic injury. In this review, we summarize the current knowledge relevant to this topic, with a focus on shear stress-induced AMPK modulation and its consequences for vascular health and disease.
Topics: Humans; AMP-Activated Protein Kinases; Endothelial Cells; Cardiovascular Diseases; Stress, Mechanical; Animals; Mechanotransduction, Cellular
PubMed: 38892235
DOI: 10.3390/ijms25116047 -
International Journal of Molecular... May 2024The deformability of red blood cells (RBCs), expressing their ability to change their shape as a function of flow-induced shear stress, allows them to optimize oxygen...
The deformability of red blood cells (RBCs), expressing their ability to change their shape as a function of flow-induced shear stress, allows them to optimize oxygen delivery to the tissues and minimize their resistance to flow, especially in microcirculation. During physiological aging and blood storage, or under external stimulations, RBCs undergo metabolic and structural alterations, one of which is hemoglobin (Hb) redistribution between the cytosol and the membrane. Consequently, part of the Hb may attach to the cell membrane, and although this process is reversible, the increase in membrane-bound Hb (MBHb) can affect the cell's mechanical properties and deformability in particular. In the present study, we examined the correlation between the MBHb levels, determined by mass spectroscopy, and the cell deformability, determined by image analysis. Six hemoglobin subunits were found attached to the RBC membranes. The cell deformability was negatively correlated with the level of four subunits, with a highly significant inter-correlation between them. These data suggest that the decrease in RBC deformability results from Hb redistribution between the cytosol and the cell membrane and the respective Hb interaction with the cell membrane.
Topics: Humans; Erythrocyte Deformability; Erythrocyte Membrane; Hemoglobins; Erythrocytes; Protein Binding
PubMed: 38892001
DOI: 10.3390/ijms25115814 -
Lasers in Surgery and Medicine Jun 2024Under optimal conditions, afferent and efferent human skin graft microcirculation can be restored 8-12 days postgrafting. Still, the evidence about the reperfusion...
OBJECTIVES
Under optimal conditions, afferent and efferent human skin graft microcirculation can be restored 8-12 days postgrafting. Still, the evidence about the reperfusion dynamics beyond this period in a dermato-oncologic setting is scant. We aimed to characterise the reperfusion of human skin grafts over 4 weeks according to the necrosis extension (less than 20%, or 20%-50%) and anatomic location using laser speckle contrast imaging (LSCI).
METHODS
Over 16 months, all eligible adults undergoing skin grafts following skin cancer removal on the scalp, face and lower limb were enroled. Perfusion was assessed with LSCI on the wound margin (control skin) on day 0 and on the graft surface on days 7, 14, 21 and 28. Graft necrosis extension was determined on day 28.
RESULTS
Forty-seven grafts of 47 participants were analysed. Regardless of necrosis extension, graft perfusion equalled the control skin by day 7, surpassed it by day 21, and stabilised onwards. Grafts with less than 20% necrosis on the scalp and lower limb shared this reperfusion pattern and had a consistently better-perfused centre than the periphery for the first 21 days. On the face, the graft perfusion did not differ from the control skin from day 7 onwards, and there were no differences in reperfusion within the graft during the study.
CONCLUSION
Skin graft reperfusion is a protracted process that evolves differently in the graft centre and periphery, influenced by postoperative time and anatomic location. A better knowledge of this process can potentially enhance the development of strategies to induce vessel ingrowth into tissue-engineered skin substitutes.
PubMed: 38890796
DOI: 10.1002/lsm.23815 -
Echocardiography (Mount Kisco, N.Y.) Jun 2024Persistent microvascular obstruction (MVO) after successful percutaneous coronary intervention (PCI) in acute ST segment elevation myocardial infarction (STEMI) has been... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Persistent microvascular obstruction (MVO) after successful percutaneous coronary intervention (PCI) in acute ST segment elevation myocardial infarction (STEMI) has been well-described. MVO predicts lack of recovery of left ventricular function and increased mortality. Sonothrombolysis utilizing diagnostic ultrasound induced cavitation of commercially available microbubble contrast has been effective at reducing infarct size and improving left ventricular ejection fraction (LVEF) when performed both pre- and post-PCI. However, the effectiveness of post-PCI sonothrombolysis alone after successful PCI has not been demonstrated.
METHODS
A prospective randomized controlled trial was performed in 50 consecutive consenting patients with anterior STEMI who underwent a continuous microbubble infusion immediately following successful PCI. Intermittent high mechanical index (MI) impulses were applied only in the sonthrombolysis group. Delayed enhancement magnetic resonance imaging (MRI) was performed at 48 h and again at 6-8 weeks to assess for differences in infarct size, LVEF, and MVO.
RESULTS
There were no differences between groups in age, gender, and cardiovascular risk factors. Significant (> 2 segments) MVO following successful PCI was observed in 66% of patients. Although sonothrombolysis reduced the extent of MVO acutely, there were no differences in infarct size, LVEF, or extent of MVO by MRI at 48 h. Twenty-eight patients returned for a follow up MRI at 6-8 weeks. LVEF improved only in the sonothrombolysis group (∆LVEF 7.81 ± 4.57% with sonothrombolysis vs. 1.77 ± 7.02% for low MI only, p = .011).
CONCLUSION
Post-PCI sonothrombolysis had minimal effect on reducing myocardial infarct size but improved left ventricular systolic function in patients with acute anterior wall STEMI.
Topics: Humans; Female; Male; Percutaneous Coronary Intervention; Middle Aged; Prospective Studies; Treatment Outcome; ST Elevation Myocardial Infarction; Recovery of Function; Myocardial Infarction; Microbubbles; Echocardiography; Microcirculation; Contrast Media; Aged
PubMed: 38889076
DOI: 10.1111/echo.15860 -
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