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BMC Pediatrics Jan 2024In children with sepsis, circulatory shock and multi-organ failure remain major contributors to mortality. Prolonged capillary refill time (PCRT) is a clinical tool...
BACKGROUNDS
In children with sepsis, circulatory shock and multi-organ failure remain major contributors to mortality. Prolonged capillary refill time (PCRT) is a clinical tool associated with disease severity and tissue hypoperfusion. Microcirculation assessment with videomicroscopy represents a promising candidate for assessing and improving hemodynamic management strategies in children with sepsis. Particularly when there is loss of coherence between the macro and microcirculation (hemodynamic incoherence). We sought to evaluate the association between PCRT and microcirculation changes in sepsis.
METHODS
This was a prospective cohort study in children hospitalized with sepsis. Microcirculation was measured using sublingual video microscopy (capillary density and flow and perfused boundary region [PBR]-a parameter inversely proportional to vascular endothelial glycocalyx thickness), phalangeal tissue perfusion, and endothelial activation and glycocalyx injury biomarkers. The primary outcome was the association between PCRT and microcirculation changes.
RESULTS
A total of 132 children with sepsis were included, with a median age of two years (IQR 0.6-12.2). PCRT was associated with increased glycocalyx degradation (PBR 2.21 vs. 2.08 microns; aOR 2.65, 95% CI 1.09-6.34; p = 0.02) and fewer 4-6 micron capillaries recruited (p = 0.03), with no changes in the percentage of capillary blood volume (p = 0.13). Patients with hemodynamic incoherence had more PBR abnormalities (78.4% vs. 60.8%; aOR 2.58, 95% CI 1.06-6.29; p = 0.03) and the persistence of these abnormalities after six hours was associated with higher mortality (16.5% vs. 6.1%; p < 0.01). Children with an elevated arterio-venous CO difference (DCO) had an abnormal PBR (aOR 1.13, 95% CI 1.01-1.26; p = 0.03) and a lower density of small capillaries (p < 0.05). Prolonged capillary refill time predicted an abnormal PBR (AUROC 0.81, 95% CI 0.64-0.98; p = 0.03) and relative percentage of blood in the capillaries (AUROC 0.82, 95% CI 0.58-1.00; p = 0.03) on admission. A normal CRT at 24 h predicted a shorter hospital stay (aOR 0.96, 95% CI 0.94-0.99; p < 0.05).
CONCLUSIONS
We found an association between PCRT and microcirculation changes in children with sepsis. These patients had fewer small capillaries recruited and more endothelial glycocalyx degradation. This leads to nonperfused capillaries, affecting oxygen delivery to the tissues. These disorders were associated with hemodynamic incoherence and worse clinical outcomes when the CRT continued to be abnormal 24 h after admission.
Topics: Child; Humans; Infant; Child, Preschool; Microcirculation; Prospective Studies; Sepsis; Capillaries; Biomarkers
PubMed: 38245695
DOI: 10.1186/s12887-024-04524-5 -
Hypertension (Dallas, Tex. : 1979) Apr 2017
Review
Topics: Awards and Prizes; Disease Progression; Humans; Kidney; Microcirculation; Renal Circulation; Renal Insufficiency, Chronic
PubMed: 28193706
DOI: 10.1161/HYPERTENSIONAHA.116.08319 -
Microcirculation (New York, N.Y. : 1994) Apr 2021Impaired tissue oxygen delivery is a major cause of organ damage and failure in critically ill patients, which can occur even when systemic parameters, including cardiac... (Review)
Review
Impaired tissue oxygen delivery is a major cause of organ damage and failure in critically ill patients, which can occur even when systemic parameters, including cardiac output and arterial hemoglobin saturation, are close to normal. This review addresses oxygen transport mechanisms at the microcirculatory scale, and how hypoxia may occur in spite of adequate convective oxygen supply. The structure of the microcirculation is intrinsically heterogeneous, with wide variations in vessel diameters and flow pathway lengths, and consequently also in blood flow rates and oxygen levels. The dynamic processes of structural adaptation and flow regulation continually adjust microvessel diameters to compensate for heterogeneity, redistributing flow according to metabolic needs to ensure adequate tissue oxygenation. A key role in flow regulation is played by conducted responses, which are generated and propagated by endothelial cells and signal upstream arterioles to dilate in response to local hypoxia. Several pathophysiological conditions can impair local flow regulation, causing hypoxia and tissue damage leading to organ failure. Therapeutic measures targeted to systemic parameters may not address or may even worsen tissue oxygenation at the microvascular level. Restoration of tissue oxygenation in critically ill patients may depend on restoration of endothelial cell function, including conducted responses.
Topics: Critical Illness; Endothelial Cells; Humans; Hypoxia; Microcirculation; Oxygen; Perfusion
PubMed: 33236393
DOI: 10.1111/micc.12673 -
Journal of Applied Physiology... Sep 2022Pulse transit time (PTT) is the time it takes for pressure waves to propagate through the arterial system. Arterial stiffness assessed via PTT has been extensively...
Pulse transit time (PTT) is the time it takes for pressure waves to propagate through the arterial system. Arterial stiffness assessed via PTT has been extensively examined in the conduit arteries; however, limited information is available about PTT to the skeletal muscle microcirculation. Therefore, the purpose of this study was to assess PTT to the skeletal muscle microcirculation (PTTm) with near-infrared spectroscopy (NIRS) and to determine whether PTTm provides unique information about vascular function that PTT assessed in the conduit arteries (PTTc) cannot provide. This pilot study was conducted with 10 (male = 5; female = 5) individuals of similar age (21.5 ± 1.2 yr). The feasibility of using the intersecting tangents method to derive PTTm with NIRS was assessed during reactive hyperemia with the cross-correlation of PTTm produced by the intersecting tangents method and a different algorithm that used signal spectral properties. To determine whether PTTm was distinct from PTTc, the cross-correlation of PTTm and PTTc during reactive hyperemia was assessed. Cross-correlation indicated agreement between PTTm derived from both algorithms ( = 0.77, < 0.01) and a lack of agreement between PTTm and PTTc during reactive hyperemia ( = 0.07, < 0.01). Therefore, we conclude that it is feasible to assess PTTm using NIRS, and PTTm provides unique information about vascular function, including skeletal muscle microvascular elasticity, which cannot be achieved with traditional PTTc. PTTm with NIRS may provide a comprehensive and noninvasive assessment of vascular function and health. Pulse transit time to the skeletal muscle microcirculation can be assessed using near-infrared spectroscopy and the intersecting tangents method. Pulse transit analysis to the microcirculation provides a comprehensive assessment of the vascular response to postocclusive reactive hyperemia that pulse transit analysis in the conduit arteries cannot provide. Pulse transit time to the skeletal muscle microcirculation using near-infrared spectroscopy provides unique information about microvascular elasticity in the skeletal muscle. These findings indicate that the combination of near-infrared spectroscopy and pulse transit analysis may be a useful method for assessing the skeletal muscle microcirculation.
Topics: Female; Humans; Hyperemia; Male; Microcirculation; Muscle, Skeletal; Pilot Projects; Pulse Wave Analysis; Spectroscopy, Near-Infrared
PubMed: 35834626
DOI: 10.1152/japplphysiol.00173.2022 -
European Heart Journal Aug 2023
Topics: Humans; Prognosis; Microcirculation; Heart; Coronary Circulation
PubMed: 37358487
DOI: 10.1093/eurheartj/ehad291 -
Trends in Endocrinology and Metabolism:... Jun 2015Insulin enhances the compliance of conduit arteries, relaxes resistance arterioles to increase tissue blood flow, and dilates precapillary arterioles to expand muscle... (Review)
Review
Insulin enhances the compliance of conduit arteries, relaxes resistance arterioles to increase tissue blood flow, and dilates precapillary arterioles to expand muscle microvascular blood volume. These actions are impaired in the insulin resistant states. Exercise ameliorates endothelial dysfunction and improves insulin responses in insulin resistant patients, but the precise underlying mechanisms remain unclear. The microvasculature critically regulates insulin action in muscle by modulating insulin delivery to the capillaries nurturing the myocytes and trans-endothelial insulin transport. Recent data suggest that exercise may exert its insulin-sensitizing effect via recruiting muscle microvasculature to increase insulin delivery to and action in muscle. The current review focuses on how the interplay among exercise, insulin action, and the vasculature contributes to exercise-mediated insulin sensitization in muscle.
Topics: Exercise; Humans; Insulin; Insulin Resistance; Microcirculation; Muscle, Skeletal
PubMed: 25735473
DOI: 10.1016/j.tem.2015.02.002 -
Anaesthesiology Intensive Therapy 2015Shock is defined as a state in which the circulation is unable to deliver sufficient oxygen to meet the demands of the tissues, resulting in cellular dysoxia and organ... (Review)
Review
Shock is defined as a state in which the circulation is unable to deliver sufficient oxygen to meet the demands of the tissues, resulting in cellular dysoxia and organ failure. In this process, the factors that govern the circulation at a haemodynamic level and oxygen delivery at a microcirculatory level play a major role. This manuscript aims to review the blood flow regulation from macro- and micro-haemodynamic point of view and to discuss new potential therapeutic approaches for cardiovascular instability in patients in cardiovascular shock. Despite the recent advances in haemodynamics, the mechanisms that control the vascular resistance and the venous return are not fully understood in critically ill patients. The physical properties of the vascular wall, as well as the role of the mean systemic filling pressure are topics that require further research. However, the haemodynamics do not totally explain the physiopathology of cellular dysoxia, and several factors such as inflammatory changes at the microcirculatory level can modify vascular resistance and tissue perfusion. Cellular vasoactive mediators and endothelial and glucocalix damage are also involved in microcirculatory impairment. All the levels of the circulatory system must be taken into account. Evaluation of microcirculation may help one to detect under-diagnosed shock, and together with classic haemodynamics, guide one towards the appropriate therapy. Restoration of classic haemodynamic parameters is essential but not sufficient to detect and treat patients in cardiovascular shock.
Topics: Cardiac Output; Glomerular Filtration Rate; Homeostasis; Humans; Microcirculation; Renal Circulation; Shock
PubMed: 26588480
DOI: 10.5603/AIT.a2015.0077 -
Journal of Cerebral Blood Flow and... Oct 2023Temporal lobe epilepsy (TLE) is increasingly associated with blood-brain barrier dysfunction and microvascular alterations, yet the pathophysiological link is missing....
Temporal lobe epilepsy (TLE) is increasingly associated with blood-brain barrier dysfunction and microvascular alterations, yet the pathophysiological link is missing. An important barrier function is exerted by the glycocalyx, a gel-like layer coating the endothelium. To explore such associations, we used intraoperative videomicroscopy to quantify glycocalyx and microcirculation properties of the neocortex and hippocampus of 15 patients undergoing resective brain surgery as treatment for drug-resistant TLE, and 15 non-epileptic controls. Fluorescent lectin staining of neocortex and hippocampal tissue was used for blood vessel surface area quantification. Neocortical perfused boundary region, the thickness of the glycocalyx' impaired layer, was higher in patients (2.64 ± 0.52 µm) compared to controls (1.31 ± 0.29 µm), 0.01, indicative of reduced glycocalyx integrity in patients. Moreover, erythrocyte flow velocity analysis revealed an impaired ability of TLE patients to (de-)recruit capillaries in response to changing metabolic demands ( = 0.75, 0.01), indicating failure of neurovascular coupling mechanisms. Blood vessel quantification comparison between intraoperative measurements and resected tissue showed strong correlation ( = 0.94, 0.01). This is the first report on assessment of glycocalyx and microcirculation properties in TLE patients, confirming the pivotal role of cerebrovascular changes. Further assessment of the cerebral microcirculation in relation to epileptogenesis might open avenues for new therapeutic targets for drug-resistant epilepsy.
Topics: Humans; Epilepsy, Temporal Lobe; Glycocalyx; Microcirculation; Blood-Brain Barrier; Capillaries
PubMed: 37231664
DOI: 10.1177/0271678X231179413 -
Oxidative Medicine and Cellular... 2021A major shortcoming of postischemic therapy for myocardial infarction is the no-reflow phenomenon due to impaired cardiac microvascular function including... (Review)
Review
A major shortcoming of postischemic therapy for myocardial infarction is the no-reflow phenomenon due to impaired cardiac microvascular function including microcirculatory barrier function, loss of endothelial activity, local inflammatory cell accumulation, and increased oxidative stress. Consequently, inadequate reperfusion of the microcirculation causes secondary ischemia, aggravating the myocardial reperfusion injury. ATP-sensitive potassium ion (K) channels regulate the coronary blood flow and protect cardiomyocytes from ischemia-reperfusion injury. Studies in animal models of myocardial ischemia-reperfusion have illustrated that the opening of mitochondrial KATP (mito-K) channels alleviates endothelial dysfunction and reduces myocardial necrosis. By contrast, blocking mito-K channels aggravates microvascular necrosis and no-reflow phenomenon following ischemia-reperfusion injury. Nicorandil, as an antianginal drug, has been used for ischemic preconditioning (IPC) due to its mito-K channel-opening effect, thereby limiting infarct size and subsequent severe ischemic insult. In this review, we analyze the protective actions of nicorandil against microcirculation reperfusion injury with a focus on improving mitochondrial integrity. In addition, we discuss the function of mitochondria in the pathogenesis of myocardial ischemia.
Topics: Animals; Humans; Microcirculation; Mitochondria; Myocardial Ischemia; Myocardial Reperfusion Injury; Nicorandil; Oxidative Stress
PubMed: 34285763
DOI: 10.1155/2021/4665632 -
Arquivos Brasileiros de Cardiologia Nov 2020
Topics: Adiposity; Endothelium, Vascular; Humans; Hypertension; Microcirculation
PubMed: 33295454
DOI: 10.36660/abc.20200574