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Cardiovascular Ultrasound May 2024Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the coronary microcirculation, which may be diagnosed using invasive...
BACKGROUND
Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the coronary microcirculation, which may be diagnosed using invasive coronary physiology. CMD is responsible for impaired diastolic cardiac function. It has recently been suggested that left atrial strain (LASr) represents a highly sensitive tool for detecting cardiac diastolic function abnormalities. Accordingly, the aim of this study was to investigate the relationship between CMD and LASr.
METHODS
Consecutively enrolled patients with non-obstructed coronary arteries (NOCA) underwent CMD and LASr evaluation by invasive thermodilution and noninvasive echocardiography, respectively.
RESULTS
Forty-two (42) patients were included, out of which 26 presented with CMD. There were no significant differences between CMD-positive and negative patients in terms of clinical and echocardiographic characteristics. LASr was significantly reduced in patients with CMD (24.6% ± 6.1 vs. 30.3 ± 7.8%, p = 0.01). A moderate correlation was observed between coronary flow reserve and LAsr (r = 0.47, p = 0.002). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LASr (OR = 0.88, 95%CI 0.78-0.99.135, p = 0.04). A LASr cut-off of 25.5% enabled an optimal classification of patients with or without CMD.
CONCLUSION
Patients with NOCA and CMD had a significantly reduced LASr compared with patients without CMD, suggesting the early impairment of diastolic function in these patients.
Topics: Humans; Male; Female; Microcirculation; Middle Aged; Coronary Circulation; Heart Atria; Echocardiography; Coronary Vessels; Coronary Artery Disease; Aged; Atrial Function, Left; Thermodilution; Diastole
PubMed: 38745211
DOI: 10.1186/s12947-024-00324-0 -
Journal of Biomedical Optics Jun 2024Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective,...
SIGNIFICANCE
Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation.
AIM
We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest.
APPROACH
Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared.
RESULTS
Diabetic patients showed significantly reduced mean BF in the neurogenic () and heart () components at the M1 and M5 regions () compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic () and myogenic () components at the M1 region, as well as in the endothelial () component at the M5 region and in the myogenic component at the dorsal foot (), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region () and heel area (). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region () and heel area () in diabetic patients.
CONCLUSIONS
This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients.
Topics: Humans; Diabetic Foot; Male; Microcirculation; Female; Laser-Doppler Flowmetry; Diabetes Mellitus, Type 2; Middle Aged; Wearable Electronic Devices; Foot; Aged; Wavelet Analysis; Adult
PubMed: 38737791
DOI: 10.1117/1.JBO.29.6.065001 -
Nature Communications May 2024Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug...
Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.
Topics: Animals; Vinca Alkaloids; Nanoparticles; Blood-Brain Barrier; Mice; Cerebrovascular Circulation; Male; Brain; Humans; Neuroprotective Agents; Mice, Inbred C57BL; Tissue Distribution; Drug Delivery Systems; Mice, Transgenic
PubMed: 38734698
DOI: 10.1038/s41467-024-48461-4 -
Diagnostics (Basel, Switzerland) Apr 2024Chronic obstructive pulmonary disease (COPD) has higher rates among the general population, so early identification and prevention is the goal. The mechanisms of COPD... (Review)
Review
BACKGROUND
Chronic obstructive pulmonary disease (COPD) has higher rates among the general population, so early identification and prevention is the goal. The mechanisms of COPD development have not been completely established, although it has been demonstrated that endothelial dysfunction plays an important role. However, to date, the measurement of endothelial dysfunction is still invasive or not fully established. Nailfold video capillaroscopy (NVC) is a safe, non-invasive diagnostic tool that can be used to easily evaluate the microcirculation and can show any possible endothelial dysfunctions early on. The aim of this review is to evaluate if nailfold microcirculation abnormalities can reflect altered pulmonary vasculature and can predict the risk of cardiovascular comorbidities in COPD patients.
METHODS
A systematic literature search concerning COPD was performed in electronic databases (PUBMED, UpToDate, Google Scholar, ResearchGate), supplemented with manual research. We searched in these databases for articles published until March 2024. The following search words were searched in the databases in all possible combinations: chronic obstructive pulmonary disease (COPD), endothelial damage, vascular impairment, functional evaluation, capillaroscopy, video capillaroscopy, nailfold video capillaroscopy. Only manuscripts written in English were considered for this review. Papers were included only if they were able to define a relationship between COPD and endothelium dysfunction.
RESULTS
The search selected 10 articles, and among these, only three previous reviews were available. Retinal vessel imaging, flow-mediated dilation (FMD), and skin autofluorescence (AF) are reported as the most valuable methods for assessing endothelial dysfunction in COPD patients.
CONCLUSIONS
It has been assumed that decreased nitric oxide (NO) levels leads to microvascular damage in COPD patients. This finding allows us to assume NVC's potential effectiveness in COPD patients. However, this potential link is based on assumption; further investigations are needed to confirm this hypothesis.
PubMed: 38732364
DOI: 10.3390/diagnostics14090950 -
Journal of Clinical Medicine Apr 2024: Coronary microvascular dysfunction is associated with adverse prognosis after ST-segment elevation myocardial infarction (STEMI). We aimed to compare the invasive,...
Correlation of Non-Invasive Transthoracic Doppler Echocardiography with Invasive Doppler Wire-Derived Coronary Flow Reserve and Their Impact on Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention.
: Coronary microvascular dysfunction is associated with adverse prognosis after ST-segment elevation myocardial infarction (STEMI). We aimed to compare the invasive, Doppler wire-based coronary flow reserve (CFR) with the non-invasive transthoracic Doppler echocardiography (TTDE)-derived CFR, and their ability to predict infarct size. : We included 36 patients with invasive Doppler wire assessment on days 3-7 after STEMI treated with primary percutaneous coronary intervention (PCI), of which TTDE-derived CFR was measured in 47 vessels (29 patients) within 6 h of the invasive Doppler. Infarct size was assessed by cardiac magnetic resonance at a median of 8 months. : The correlation between invasive and non-invasive CFR was modest in the overall cohort (rho 0.400, = 0.005). It improved when only measurements in the LAD artery were considered (rho 0.554, = 0.002), with no significant correlation in the RCA artery (rho -0.190, = 0.435). Both invasive (AUC 0.888) and non-invasive (AUC 0.868) CFR, measured in the recanalized culprit artery, showed a good ability to predict infarct sizes ≥18% of the left ventricular mass, with the optimal cut off values of 1.85 and 1.80, respectively. : In patients with STEMI, TTDE- and Doppler wire-derived CFR exhibit significant correlation, when measured in the LAD artery, and both have a similarly strong association with the final infarct size.
PubMed: 38731013
DOI: 10.3390/jcm13092484 -
Canadian Journal of Physiology and... May 2024Coronary microvascular dysfunction (CMD) involves functional or structural abnormalities of the coronary microvasculature resulting in dysregulation of coronary blood...
Coronary microvascular dysfunction (CMD) involves functional or structural abnormalities of the coronary microvasculature resulting in dysregulation of coronary blood flow (CBF) in response to myocardial oxygen demand. This perfusion mismatch causes myocardial ischemia, which manifests in patients as microvascular angina (MVA). CMD can be diagnosed non-invasively via multiple imaging techniques or invasively using coronary function testing (CFT), which assists in determining the specific mechanisms involving endothelium-independent and dependent epicardial and microcirculation domains. Unlike traditional coronary artery disease (CAD), CMD can often occur in patients without obstructive atherosclerotic epicardial disease, which can make the diagnosis of CMD difficult. Moreover, MVA due to CMD is more prevalent in women and carries increased risk of future cardiovascular events. Successful treatment of symptomatic CMD is often patient-specific risk factor and endotype targeted. This article aims to review newly identified mechanisms and novel treatment strategies for managing CMD, and outline sex-specific differences in the presentation and pathophysiology of the disease.
PubMed: 38728748
DOI: 10.1139/cjpp-2023-0414 -
Biomicrofluidics May 2024The role of the circulatory system, containing the blood and lymphatic vasculatures, within the body, has become increasingly focused on by researchers as dysfunction of... (Review)
Review
The role of the circulatory system, containing the blood and lymphatic vasculatures, within the body, has become increasingly focused on by researchers as dysfunction of either of the systems has been linked to serious complications and disease. Currently, models are unable to provide the sufficient monitoring and level of manipulation needed to characterize the fluidic dynamics of the microcirculation in blood and lymphatic vessels; thus models have been pursued as an alternative model. Microfluidic devices have the required properties to provide a physiologically relevant circulatory system model for research as well as the experimental tools to conduct more advanced research analyses of microcirculation flow. In this review paper, the physiological behavior of fluid flow and electrical communication within the endothelial cells of the systems are detailed and discussed to highlight their complexities. Cell co-culturing methods and other relevant organ-on-a-chip devices will be evaluated to demonstrate the feasibility and relevance of the microfluidic model. Microfluidic systems will be determined as a noteworthy model that can display physiologically relevant flow of the cardiovascular and lymphatic systems, which will enable researchers to investigate the systems' prevalence in diseases and identify potential therapeutics.
PubMed: 38726373
DOI: 10.1063/5.0175154 -
PNAS Nexus Feb 2024Blood velocity and red blood cell (RBC) distribution profiles in a capillary vessel cross-section in the microcirculation are generally complex and do not follow...
Blood velocity and red blood cell (RBC) distribution profiles in a capillary vessel cross-section in the microcirculation are generally complex and do not follow Poiseuille's parabolic or uniform pattern. Existing imaging techniques used to map large microvascular networks in vivo do not allow a direct measurement of full 3D velocity and RBC concentration profiles, although such information is needed for accurate evaluation of the physiological variables, such as the wall shear stress (WSS) and near-wall cell-free layer (CFL), that play critical roles in blood flow regulation, disease progression, angiogenesis, and hemostasis. Theoretical network flow models, often used for hemodynamic predictions in experimentally acquired images of the microvascular network, cannot provide the full 3D profiles either. In contrast, such information can be readily obtained from high-fidelity computational models that treat blood as a suspension of deformable RBCs. These models, however, are computationally expensive and not feasible for extension to the microvascular network at large spatial scales up to an organ level. To overcome such limitations, here we present machine learning (ML) models that bypass such expensive computations but provide highly accurate and full 3D profiles of the blood velocity, RBC concentration, WSS, and CFL in every vessel in the microvascular network. The ML models, which are based on artificial neural networks and convolution-based U-net models, predict hemodynamic quantities that compare very well against the true data but reduce the prediction time by several orders. This study therefore paves the way for ML to make detailed and accurate hemodynamic predictions in spatially large microvascular networks at an organ-scale.
PubMed: 38725529
DOI: 10.1093/pnasnexus/pgae043 -
Journal of Zhejiang University.... Mar 2024Pheochromocytomas and paragangliomas (PPGLs) cause symptoms by altering the circulation levels of catecholamines and peptide hormones. Currently, the diagnosis of PPGLs...
Pheochromocytomas and paragangliomas (PPGLs) cause symptoms by altering the circulation levels of catecholamines and peptide hormones. Currently, the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines. In this study, we used ultra-performance liquid chromatography (UPLC)/quadrupole time-of-flight mass spectrometry (Q-TOF MS) analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients. We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla. Through conducting two steps of metabolomics analysis, we identified 111 differential metabolites between the healthy group and the patient group, among which 53 metabolites were validated. By integrating the information of differential metabolites and differentially expressed genes, we inferred that the cysteine-methionine, pyrimidine, and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm. The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma, whereas the pyrimidine pathway showed no significant difference. Finally, we developed an optimized diagnostic model of two metabolites, L-dihydroorotic acid and vanylglycol. Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.
Topics: Pheochromocytoma; Humans; Adrenal Gland Neoplasms; Pyrimidines; Methionine; Tyrosine; Cysteine; Male; Metabolomics; Female; Middle Aged; Adult; Metabolic Networks and Pathways
PubMed: 38725340
DOI: 10.1631/jzus.B2300579 -
Scientific Reports May 2024This study aims to measure myocardial blood flow (MBF) using dynamic CT- myocardial perfusion imaging (CT-MPI) combined with mental stressors in patients with...
Computed tomography myocardial perfusion imaging to detect myocardial ischemia in patients with anxiety and obstructive coronary heart disease post-exposure to mental stressors.
This study aims to measure myocardial blood flow (MBF) using dynamic CT- myocardial perfusion imaging (CT-MPI) combined with mental stressors in patients with obstructive coronary artery disease (OCAD) and in patients with anxiety and no obstructive coronary artery disease (ANOCAD). A total of 30 patients with OCAD with 30 patients with ANOCAD were included in this analysis. Using the 17-segment model, the rest and stress phase MBF of major coronary arteries in participants were recorded respectively. Compared with ANOCAD patients, OCAD patients were more likely to have localized reduction of MBF (p < 0.05). For patients with ANOCAD, both global MBF and MBF of the main coronary arteries in the stress phase were lower than those in the rest phase (all p < 0.05), but there was no significant difference in MBF among the main coronary arteries in the rest or stress phase (p = 0.25, p = 0.15). For patients with OCAD, the MBF of the target area was lower than that of the non-target area in both the rest and stress phase, and the MBF of the target area in the stress phase was lower than that in the rest phase (all p < 0.05). However, there was no significant difference in MBF between the rest or stress phase in the non-target area (p = 0.73). Under mental stress, the decrease in MBF in ANOCAD patients was diffuse, while the decrease in MBF in OCAD patients was localized. Dynamic CT-MPI combined with mental stressors can be used to detect MBF changes in anxiety patients.
Topics: Humans; Male; Female; Myocardial Perfusion Imaging; Middle Aged; Stress, Psychological; Anxiety; Myocardial Ischemia; Aged; Tomography, X-Ray Computed; Coronary Artery Disease; Coronary Circulation; Coronary Vessels
PubMed: 38724607
DOI: 10.1038/s41598-024-61568-4