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Critical Care Medicine Apr 2021In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia.
OBJECTIVES
In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia.
DESIGN
Multicenter case-controlled study.
SETTING
Two ICUs in The Netherlands and one in Switzerland.
PATIENTS
Thirty-four critically ill coronavirus disease 2019 patients were compared with 33 healthy volunteers.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
The microcirculatory parameters quantified included total vessel density (mm × mm-2), functional capillary density (mm × mm-2), proportion of perfused vessels (%), capillary hematocrit (%), the ratio of capillary hematocrit to systemic hematocrit, and capillary RBC velocity (μm × s-1). The number of leukocytes in capillary-postcapillary venule units per 4-second image sequence (4 s-1) and capillary RBC microaggregates (4 s-1) was measured. In comparison with healthy volunteers, the microcirculation of coronavirus disease 2019 patients showed increases in total vessel density (22.8 ± sd 5.1 vs 19.9 ± 3.3; p < 0.0001) and functional capillary density (22.2 ± 4.8 vs 18.8 ± 3.1; p < 0.002), proportion of perfused vessel (97.6 ± 2.1 vs 94.6 ± 6.5; p < 0.01), RBC velocity (362 ± 48 vs 306 ± 53; p < 0.0001), capillary hematocrit (5.3 ± 1.3 vs 4.7 ± 0.8; p < 0.01), and capillary-hematocrit-to-systemic-hematocrit ratio (0.18 ± 0.0 vs 0.11 ± 0.0; p < 0.0001). These effects were present in coronavirus disease 2019 patients with Sequential Organ Failure Assessment scores less than 10 but not in patients with Sequential Organ Failure Assessment scores greater than or equal to 10. The numbers of leukocytes (17.6 ± 6.7 vs 5.2 ± 2.3; p < 0.0001) and RBC microaggregates (0.90 ± 1.12 vs 0.06 ± 0.24; p < 0.0001) was higher in the microcirculation of the coronavirus disease 2019 patients. Receiver-operating-characteristics analysis of the microcirculatory parameters identified the number of microcirculatory leukocytes and the capillary-hematocrit-to-systemic-hematocrit ratio as the most sensitive parameters distinguishing coronavirus disease 2019 patients from healthy volunteers.
CONCLUSIONS
The response of the microcirculation to coronavirus disease 2019-induced hypoxemia seems to be to increase its oxygen-extraction capacity by increasing RBC availability. Inflammation and hypercoagulation are apparent in the microcirculation by increased numbers of leukocytes and RBC microaggregates.
Topics: COVID-19; Capillaries; Erythrocytes; Female; Humans; Hypoxia; Leukocytes; Male; Microcirculation; Middle Aged
PubMed: 33405410
DOI: 10.1097/CCM.0000000000004862 -
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 -
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 -
Pediatric Rheumatology Online Journal Oct 2023Pediatric uveitis is a severe inflammatory ocular condition that can lead to sight-threatening complications and can negatively impact quality of life. The retinal...
BACKGROUND
Pediatric uveitis is a severe inflammatory ocular condition that can lead to sight-threatening complications and can negatively impact quality of life. The retinal microcirculation is often affected in intermediate uveitis and panuveitis. Here, we examined the extraocular (i.e., systemic) microcirculation in pediatric uveitis cases and healthy controls using nailfold capillaroscopy (NFC).
METHODS
We performed NFC in 119 children with noninfectious uveitis and 25 healthy pediatric controls, and assessed the following parameters: capillary density (number of capillaries/mm), dilated capillaries (apex > 20 µm), avascular area, the presence of microhemorrhages, and capillary morphology. Differences in NFC parameters between cases and controls were calculated using regression analysis after adjusting for age and sex.
RESULTS
The mean (± SD) age of the patient group was 13.7 (± 3) years, with 56% females; 46%, 18%, and 36% of cases presented as anterior uveitis, intermediate uveitis, and panuveitis, respectively, with an overall mean disease duration of 4.7 (± 4.0) years. Compared to the control group, the pediatric uveitis cases had a significantly higher number of dilated capillaries/mm and a higher prevalence of ramified capillaries. Moreover, compared to the control group the intermediate uveitis cases had a significantly higher number of dilated capillaries, whereas the anterior uveitis cases had a lower capillary density and a higher prevalence of ramified capillaries.
CONCLUSIONS
Children with uveitis without systemic disease can present with changes in systemic microcirculation. These changes vary amongst the subtypes of uveitis.
Topics: Female; Humans; Child; Adolescent; Male; Microcirculation; Quality of Life; Nails; Uveitis; Uveitis, Anterior; Uveitis, Intermediate; Panuveitis; Microscopic Angioscopy
PubMed: 37784087
DOI: 10.1186/s12969-023-00896-7 -
Physiology & Behavior Oct 2020Neurally mediated anticipatory responses, also named cephalic-phase responses, and microcirculatory regulation are two important mechanisms to maintain metabolic... (Randomized Controlled Trial)
Randomized Controlled Trial
Neurally mediated anticipatory responses, also named cephalic-phase responses, and microcirculatory regulation are two important mechanisms to maintain metabolic homeostasis. Altered cephalic-phase responses in obesity and its metabolic consequences have been proposed. There is, however, a lack of studies focusing on in vivo assessment of the microcirculation during this phase in patients with obesity. In this randomized controlled trial, we selected patients with obesity and healthy subjects after clinical and laboratory assessments. Those with obesity were randomized into two groups: experimental (cephalic-phase microvascular response stimulation - CP group, n = 13) and controls (n = 14). Healthy subjects (n = 17) were also included to form a CP control group. Skin microvascular assessment was used as a model of systemic microcirculation. Resting functional capillary density (FCD) and peak FCD during post-occlusive reactive hyperemia (PORH) were measured by dorsal finger videocapillaroscopy and expressed mainly capillary recruitment capacity. Resting red blood cell velocity (RBCV), peak RBCV during PORH (RBCV), and time taken to reach RBCV (TRBCV) were assessed by dynamic nailfold videocapillaroscopy and expressed the microhemodynamics. Patients with obesity (with or without stimulus) failed to show an increase on FCD during PORH post-stimulus (p = 0.221 and p = 0.307, respectively) depicting lack of capillary recruitment. In contrast, healthy subjects presented an increase in this microvascular outcome (p = 0.004). Changes in all variables of microhemodynamics occurred in both CP groups (healthy and those with obesity). During CP, we originally demonstrated an absence of capillary recruitment in subjects with obesity. These findings might contribute to the literature of microvascular impairment and metabolic conditions.
Topics: Capillaries; Erythrocytes; Humans; Microcirculation; Microscopic Angioscopy; Obesity; Skin
PubMed: 32707159
DOI: 10.1016/j.physbeh.2020.113087 -
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 -
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 -
Journal of Cerebral Blood Flow and... Dec 2022Systemic inflammation affects cognitive functions and increases the risk of dementia. This phenomenon is thought to be mediated in part by cytokines that promote...
Systemic inflammation affects cognitive functions and increases the risk of dementia. This phenomenon is thought to be mediated in part by cytokines that promote neuronal survival, but the continuous exposure to which may lead to neurodegeneration. The effects of systemic inflammation on cerebral blood vessels, and their provision of adequate oxygen to support critical brain parenchymal cell functions, remains unclear. Here, we demonstrate that neurovascular coupling is profoundly disturbed in lipopolysaccharide (LPS) induced systemic inflammation in awake mice. In the 24 hours following LPS injection, the hyperaemic response of pial vessels to functional activation was attenuated and delayed. Concurrently, under steady-state conditions, the capillary network displayed a significant increase in the number of capillaries with blocked blood flow, as well as increased duration of 'capillary stalls'-a phenomenon previously reported in animal models of stroke and Alzheimer's disease pathology. We speculate that vascular changes and impaired oxygen availability may affect brain functions following acute systemic inflammation and contribute to the long-term risk of neurodegenerative changes associated with chronic, systemic inflammation.
Topics: Animals; Mice; Microcirculation; Lipopolysaccharides; Disease Models, Animal; Inflammation; Capillaries; Hyperemia; Oxygen
PubMed: 35999817
DOI: 10.1177/0271678X221112278 -
Cardiovascular Research Dec 2022The human gut microbiota is the microbial ecosystem in the small and large intestines of humans. It has been naturally preserved and evolved to play an important role in... (Review)
Review
Mechanisms, therapeutic implications, and methodological challenges of gut microbiota and cardiovascular diseases: a position paper by the ESC Working Group on Coronary Pathophysiology and Microcirculation.
The human gut microbiota is the microbial ecosystem in the small and large intestines of humans. It has been naturally preserved and evolved to play an important role in the function of the gastrointestinal tract and the physiology of its host, protecting from pathogen colonization, and participating in vitamin synthesis, the functions of the immune system, as well as glucose homeostasis and lipid metabolism, among others. Mounting evidence from animal and human studies indicates that the composition and metabolic profiles of the gut microbiota are linked to the pathogenesis of cardiovascular disease, particularly arterial hypertension, atherosclerosis, and heart failure. In this review article, we provide an overview of the function of the human gut microbiota, summarize, and critically address the evidence linking compositional and functional alterations of the gut microbiota with atherosclerosis and coronary artery disease and discuss the potential of strategies for therapeutically targeting the gut microbiota through various interventions.
Topics: Animals; Humans; Cardiovascular Diseases; Gastrointestinal Microbiome; Microcirculation; Ecosystem; Atherosclerosis
PubMed: 35420126
DOI: 10.1093/cvr/cvac057