Endogenous chemical mediators of vascular smooth muscle tone.

Endogenous chemical mediators of vascular smooth muscle tone.

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Fluid selection and administration during shock is typically guided by consideration of macrovascular abnormalities and resuscitative targets (perfusion parameters, heart rate, blood pressure, cardiac output). However, the microcirculatory unit (comprised of arterioles, true capillaries, and venules) is vital for the effective delivery of oxygen an...

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... tone can be influenced by numerous chemical mediators in the circulation, such as catecholamines, endothelin and thromboxane (Table 1). Catecholamines are important (predominantly) vasoconstrictor agents released in large amounts when the sympathetic nervous system is activated. ...
Context 2
... tissue bed requirements vary based on their metabolic rate, nutrient availability and accumulation of waste products. Given that each capillary bed has unique requirements that may change independent of nearby capillary beds or systemic tissue needs, there are many local regulators of microcirculatory flow ( Table 1). Typically, these changes in perfusion occur at the level of the precapillary sphincter. ...

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... pertaining to its effect on the EG. 18 Our findings align with literature that supports the conservative and judicious use of IV fluids. [11][12][13][19][20][21] High plasma and serum concentrations of shed EG components have been associated with increased morbidity and mortality, but the clinical relevance of increased urine SDC1 concentration remains undefined and requires more investigation. ...
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Background Syndecan‐1 (SDC1) is an established marker of endothelial glycocalyx shedding. Most research on SDC1 has focused on plasma or serum concentrations, and little is known about urine concentrations. Objectives Measure urinary SDC1 concentrations in dogs undergoing anesthesia with either sevoflurane or isoflurane and assess the effects of anesthesia duration and IV crystalloids on urinary SDC1 concentrations. Animals Thirty‐one client‐owned dogs undergoing anesthesia for magnetic resonance imaging (MRI) with or without surgery for suspected intervertebral disk disease (IVDD) were used. Methods Dogs with suspected IVDD were randomized to undergo anesthesia with either sevoflurane or isoflurane. Urine was collected before and immediately after anesthesia for the analysis of SDC1. Urinary creatinine concentrations also were measured, and the ratio of urinary SDC1 to urinary creatinine (USCR) was used to account for dilution. Results Median (range) USCR was significantly higher after anesthesia compared with baseline for all groups combined (P < .05). No significant difference was found between the groups for age, sex, weight, and type of anesthesia. Multiple regression analysis of the effect of the independent variables inhalant type, age, weight, sex, anesthesia time, surgery, and quantity of IV fluids on the dependent variable SDC1 found that only the quantity of IV fluids significantly predicted a change (P < .001). Conclusions and Clinical Importance The total volume of lactated Ringer's solution administered to anesthetized dogs may affect USCR. Further investigations are warranted to evaluate the relationship between IV fluids and SDC1.
... VD and MFI have gained increasing attention as crucial assessments for haemodynamic changes and systemic microcirculation disorders in critically ill patients. Research on microcirculation evaluation in sepsis and critical care monitoring has shown that VD and MFI can determine the fluid resuscitation needs of ICU patients [22,23]. There is currently a lack of relevant research on VD and MFI for assessing SLE-PAH. ...
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Objective To investigate the role of eye signs in predicting poor outcomes in systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH). Methods This prospective observational study recruited patients diagnosed with SLE-PAH from Jan. 2021 to Dec. 2021 at the First Affiliated Hospital of Nanchang University; those with other potential causes of PAH were excluded. The evaluation of various parameters, such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), echocardiography, and risk stratification based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines, was conducted at intervals of every 1–3 months, and a 6-month follow-up period was observed. The primary outcome measure considered improvement if there was a decline in the risk stratification grade at the end point and unimproved if there was no decline. Conjunctival microvascular images were observed and recorded. Results A total of 29 SLE-PAH patients were enrolled, comprising 12 in the improved group and 17 in the nonimproved group. All SLE-PAH patients showed various manifestations of eye signs, including vessel twisting, dilation, ischaemic areas, haemorrhages, reticulum deformity, and wound spots. The nonimproved group exhibited significantly lower vessel density (VD) and microvascular flow index (MFI) of conjunctival microvascular images than the improved group. Correlation analysis revealed that VD displayed a negative correlation with the WHO-FC ( r = −0.413, p = 0.026) and NT-proBNP ( r = −0.472, p = 0.010), as well as a positive correlation with the 6MWD ( r = 0.561, p = 0.002). Similarly, MFI exhibited a negative correlation with WHO-FC ( r = −0.408, p = 0.028) and NT-proBNP ( r = −0.472, p = 0.010) and a positive correlation with 6MWD ( r = 0.157, p = 0.004). Multivariate logistic regression analysis indicated that VD (OR 10.11, 95% CI 1.95–52.36), MFI (OR 7.85, 95% CI 1.73–35.67), NT-proBNP, and 6MWD were influential factors in predicting the prognostic improvement of SLE-PAH patients. ROC curve analysis demonstrated that VD, MFI, 6MWD, and NT-proBNP (with respective AUC values of 0.83, 0.83, 0.76, and 0.90, respectively) possessed a sensitivity and specificity of 75 and 100%, as well as 83 and 100%, respectively. Regarding prognostic prediction, VD and MFI exhibited higher sensitivity than 6MWD, whereas MFI displayed higher sensitivity and specificity than NT-proBNP. Conclusion SLE-PAH can lead to various conjunctival microvascular manifestations in which vascular density and microvascular flow index can be used to assess cardiopulmonary function and predict therapeutic efficacy and prognosis in SLE-PAH patients.
... A review by Smart et al. explored evidence from preclinical and animal studies that suggested restrictive and/or slow fluid administration may be beneficial in these states, for instance, by reducing the deleterious early inflammatory response and decreasing subsequent vasopressor requirements [22]. It is proposed that restrictive regimens avoid fluid-mediated EG injury occurring via mechanisms such as release of EG-shedding matrix metalloproteinase in response to vascular stretching; oscillatory shear stress-induced activation of cathepsin L; facilitation of neutrophil-elastase-related EG shedding; and release of ANP causing EG degradation [48]. Such microcirculatory dysfunction may persist and lead to poorer outcomes despite initial improvement in macrohemodynamic markers. ...
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This systematic review identified 20 clinical studies that assessed the relationship between IV fluid administration and indicators of EG shedding in people. Across ten studies involving 1360 patients with sepsis or critical illness, it was found that EG markers were significantly elevated at baseline, but not consistently associated with rate or volume of IV fluid administration. Conversely, among nine studies of 600 stable and perioperative participants, there was a more consistent association between volume/rate of fluid administration and measures of EG shedding. These patterns were most evident when examining plasma Syn-1 concentration. Measurement of other biomarkers (e.g., Syn-4, hyaluronan and HS), as well as other methods of estimating EG thickness, were less frequently studied. The studies did not demonstrate a consistent relationship between rate/volume of fluid administration and natriuretic peptides, hemodynamic outcomes, or clinical outcomes such as length-of-stay and mortality.
... decreased, hypoxia perpetuates an inflammatory response and subsequent endothelial dysfunction. [3][4] Injury to and pathology of the microvasculature results in EGC shedding and degradation, resulting in increased permeability and pathological cellular interactions, ultimately playing a role in the development of systemic inflammatory response syndrome, coagulopathy, and multiple organ failure. 2 Therefore, there may be significant clinical implications associated with EGC shedding and microcirculatory dysfunction. Further, normalization of macrocirculatory parameters does not necessarily equate to normalization of microcirculatory parameters and reversal of pathologic derangements. ...
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OBJECTIVE To investigate the effects of hemorrhagic shock and fresh whole blood resuscitation on the microcirculation and endothelial glycocalyx using sidestream dark field (SDF) imaging and plasma biomarkers. ANIMALS 8 purpose-bred dogs. METHODS Pressure-targeted hemorrhagic shock was induced in anesthetized dogs. SDF measurement of perfused boundary region and microcirculatory variables (RBC flow, total vessel density, and relative and absolute capillary blood volume), biomarker measurement (heparan sulfate, hyaluronan, VE-cadherin, and syndecan-1), mean arterial blood pressure, and cardiac output measurement were performed before anesthesia (TP0), after induction (TP1), after hemorrhagic shock (TP2), and after 50% retransfusion (TP3) and 100% retransfusion (TP4). RESULTS At TP1, TP2, TP3, and TP4, mean arterial blood pressure was 74.25 ± 7.17 mm Hg, 49.50 ± 13.74 mm Hg, 63.50 ± 13.29 mm Hg, and 71.38 ± 8.77 mm Hg, and cardiac output was 2.57 ± 1.01 L/min, 0.8 ± 0.36 L/min, 1.81 ± 0.57 L/min, and 2.93 ± 1.22 L/min, respectively. Heparan sulfate, hyaluronan, syndecan-1, and VE-cadherin ranges were 24.80 to 77.72 ng/mL, 5.77 to 105.06 ng/mL, below detection to 1,545.69 pg/mL, and 0 to 2.52 ng/mL, respectively. Perfused boundary region, RBC flow, total vessel density, and relative and absolute capillary blood volume ranges were 1.75 to 2.68 µm, 89.6 to 584.5 µm/s, 51.7 to 1,914.3 mm/m ² , 0.94 to 1.53 10 ³ μm ³ , and 1.50 to 94.30 10 ³ μm ³ , respectively. Heparan sulfate decreased significantly over time ( P = .016). No significant differences were found for microcirculatory variables, perfused boundary regions, or other biomarkers. CLINICAL RELEVANCE This was the first study to assess microvascular dysfunction and endothelial shedding in a canine hemorrhagic shock model using SDF microscopy (Glycocheck) and plasma biomarkers. Further studies are needed to determine clinical relevance.
... However, even if septic shock patients get the MAP target above 65 mmHg, the 90-day mortality was still around 40% [8,22]. Numerous studies have confirmed that there are still microcirculation disorders after shock resuscitation [23,24]. DBP was the only independent microcirculatory determinant of tissue oxygen saturation resaturation (resStO 2 ) [25], which was measured by Near infrared spectrometry as one of the main studied microcirculation parameters and strongly associated with outcome in sepsis patients [26,27]. ...
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Background: Although the mean arterial pressure (MAP) target of 65 mmHg was achieved, diastolic blood pressure (DBP) was still low in some septic shock patients. The effects of DBP on the prognosis and optimal target for patients with septic shock are unclear. We sought to investigate the relationship between DBP and 28-day mortality in septic shock patients. Methods: In this retrospective observational study, we obtained data from the Chinese Database in Intensive Care (CDIC). We included patients with an admission diagnosis of septic shock and shock was controlled. DBP was measured every 1 h, and the mean DBP during the first 24 h (mDBP24h) was recorded. The primary outcome was 28-day mortality. Multivariable logistic regression determined the relationship between mDBP24h and 28-day mortality. Results: In total, 1251 patients were finally included. The 28-day mortality of included septic shock patients was 28.3%. The mDBP24h, not mSBP24h, was higher among 28-day survivors compared with non-survivors. 28-day mortality was inversely associated with mDBP24h (unadjusted OR 0.814 per 10 mmHg higher mDBP24h, P = 0.003), with a stepwise increase in 28-day mortality at lower mDBP24h. The 28-day mortality of patients with mDBP24h < 59 mmHg had an absolute risk reduction of 9.4% (P = 0.001). And mDBP24h < 59 mmHg was the remaining high risk factor inversely associated with 28-day mortality after multivariable adjustment (adjusted OR 1.915, 95% CI 1.037-3.536, P = 0.038), while mMAP24h and mSBP24h were not. Conclusion: In patients with septic shock after initial resuscitation, we observed an inverse association between mDBP24h and 28-day mortality. The poor outcomes in patients with mDBP24h < 59 mmHg provide indirect evidence supporting a further DBP goal of 59 mmHg for patients with septic shock after MAP of 65 mmHg was achieved.
... For most patients, the total infusion volume of 2,500-4,000 ml is enough to reach the recovery goal within the first 24 h. Effective fluid management can reduce the inflammatory response of the patient, enhance immune function and improve survival rates (94). Furthermore, microcirculatory monitoring can help diagnose occult shock (95). ...
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Severe acute pancreatitis (SAP) is a severe disease with a high prevalence and a 3-15% mortality worldwide, and premature activation of zymogen for any reason is the initial factor for the onset of SAP. Gallstone disease and heavy alcohol consumption are the two most common etiologies of SAP. Persistent inflammation, immunosuppression and catabolism syndrome (PICS) is a life-threatening illness, and there are no effective treatments. The relapse state of PICS mainly leads to high mortality due to septic shock or severe trauma, both of which are dangerous and challenging conditions for clinicians. Thus, it is important for medical staff to identify patients at high risk of PICS and to master the prevention and treatment of PICS in patients with SAP. The present review aims to increase the understanding of the pathogenesis of PICS, produce evidence for PICS diagnosis and highlight clinical treatment for PICS in patients with SAP. With this information, clinical workers could implement standardized and integrated measures at an early stage of SAP to stop its progression to PICS.
... VD and MFI have gained increasing attention as crucial assessments for hemodynamic changes and systemic microcirculation disorder in critically ill patients. Research on microcirculation evaluation in sepsis and critical care monitoring has shown that VD and MFI can determine the uid resuscitation needs of ICU patients [20,21]. There is currently a lack of relevant research on VD and MFI for assessing SLE-PAH. ...
Preprint
Full-text available
Objective To investigate the role of eye signs in predicting poor outcome of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH). Methods This prospective observational study recruited the patients diagnosed with SLE-PAH from Jan. 2010 to Dec. 2010 at the first affiliated hospital of Nanchang University, while those with other potential causes of PAH were excluded. the evaluation of various parameters such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walking distance(6MWD), World Health Organization functional class (WHO-FC), echocardiography, and risk stratification based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines were conducted at intervals of every 1–3 months, and a 6-month follow-up period was observed. The primary outcome measure considered improvement if there was a decline in the risk stratification grade at the end point, and unimproved if there was no decline. Conjunctival microvasculation images were observed and recorded. Results A total of 29 SLE-PAH patients were enrolled, comprising 12 in the improved group and 17 in the non-improved group. ALL SLE-PAH show various manifestions in eye signs including vessel twisting, dilation, ischemic areas, hemorrhages, reticulum deformity, and wound spots. The non-improved group exhibited significantly lower vessel density (VD) and microvascular flow index (MFI) of conjuctival microvasculation images compared to the improved group. Correlation analysis revealed that VD displayed a negative correlation with the WHO-FC(r=-0.413, p = 0.026)and NT-proBNP (r=-0.472, p = 0.010), as well as a positive correlation with the 6MWD(r = 0.561, p = 0.002). Similarly, MFI exhibited a negative correlation with WHO-FC (r=-0.408, p = 0.028), and NT-proBNP (r=-0.472, p = 0.010), and a positive correlation with 6MWD (r = 0.157, p = 0.004). Multivariate logistic regression analysis indicated that VD (OR 10.11, 95% CI 1.95–52.36), MFI (OR 7.85, 95% CI 1.73–35.67), NT-proBNP, and 6MWD were influential factors in predicting the prognostic improvement of SLE-PAH patients. ROC curve analysis demonstrated that VD, MFI, 6MWD, and NT-proBNP (with respective ROC AUC values of 0.83, 0.83, 0.76, and 0.90) possessed a sensitivity and specificity of 75% and 100%, as well as 83% and 100%, respectively. Regarding prognostic prediction, VD and MFI exhibited higher sensitivity compared to 6MWD, whereas MFI displayed higher sensitivity and specificity compared to NT-proBNP. Conclusion SLE-PAH can lead to various conjuctival microvascular manifestions in which vascular density and microvascular flow index can be used to assess the cardiopulmonary function and predict therapeutic efficacy and prognosis in SLE-PAH patients.
... The microvascular unit is comprised of arterioles, post capillary venules, capillaries and their sub cellular components (2). In recent years, the endothelial glycocalyx (eGC) has been recognized as an important part of that microvascular unit (3). The eGC is a gel-like structure that covers the luminal surface of the vascular endothelium, and is composed of a network of glycosaminoglycans, glycoproteins, and proteoglycans with the predominant glycosaminoglycans being heparin sulfate, chondroitin sulfate, and hyaluronan (4)(5)(6). ...
... The eGC has been recognized for its pivotal role in regulating hemostasis, permeability, and inflammation (7). The microcirculation is commonly assessed at the sublingual mucosa using hand-held sidestream dark field (SDF) videomicroscopy (2,3,8). Recently, a novel SDF video microscope 1 has been launched, which combines microcirculation video microscopy and measures the perfused boundary region (PBR) as a surrogate for eGC thickness (9)(10)(11)(12). ...
... Changes in HR, lactate and Flow between 2 specific time points are consistent with a hemorrhagic shock model using a different SDF video microscope (28). The discrepancy between macrocirculatory changes and microcirculatory derangements, or loss of hemodynamic coherence is very well described in the veterinary literature (3). ...
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Introduction To evaluate microcirculation and endothelial glycocalyx (eGC) variables using sidestream darkfield (SDF) videomicroscopy in canine cardiopulmonary bypass (CPB). Methods Dogs undergoing CPB for surgical correction of naturally-occurring cardiac disease were prospectively included. Variables collected included patient demographics, underlying cardiac disease, red blood cell flow (Flow), 4-25 μm vessel density (Density), absolute capillary blood volume (CBVabs), relative capillary blood volume (CBVrel) and eGC width assessed by perfused boundary region (PBR). Anesthetized healthy dogs were used as control. Microcirculation and eGC variables were compared at baseline under anesthesia (T0), on CPB prior to cross clamping (T1), after cross clamp removal following surgical correction (T2) and at surgical closure (T3). Results Twelve dogs were enrolled, including 10 with a complete dataset. Median Flow was 233.9, 79.9, 164.3, and 136.1 μm/s at T0, T1, T2, and T3, respectively, (p = 1.00). Median Density was 173.3, 118.4, 121.0 and 155.4 mm/mm² at T0, T1, T2, and T3, respectively, (p = 1.00). Median CBVabs decreased over time: 7.4, 6.6, 4.8 and 4.7 10³μm³ at T0, T1, T2, and T3, respectively, (p < 0.01). Median CBVrel increased over time: 1.1, 1.5,1.1, and 1.3 10³μm³ at T0, T1, T2, and T3, respectively, (p < 0.001). Median PBR increased over time: 1.8, 2.1, 2.4, 2.1 μm at T0, T1, T2, and T3, respectively, (p < 0.001). Compared to control dogs (n = 8), CPB dogs had lower CBVabs at T0. Conclusion Alterations in eGC thickness and microvascular occur in dogs undergoing CPB for naturally-occurring cardiac disease.
... However, even if septic shock patients get the MAP target above 65mmHg, the 90 day mortality was still around 40% [8,21]. Numerous studies have con rmed that there are still microcirculation disorders after shock resuscitation [22,23]. DBP was the only independent macrocirculatory determinant of tissue oxygen saturation resaturation (resStO 2 ) [24], which was measured by Near infrared spectrometry as one of the main studied microcirculation parameters and strongly associated with outcome in sepsis patients [25,26]. ...
Preprint
Full-text available
Background: Although the mean arterial pressure (MAP) target of 65mmHg was achieved, diastolic blood pressure (DBP) was still low in some septic shock patients. The effects of DBP on the prognosis and optimal target for patients with septic shock remains unknown. We sought to investigate the relationship between DBP and mortality at 28 days in septic shock patients. Methods: In this retrospective observational study, we obtained data from the Chinese Database in Intensive Care (CDIC). We included patients with an admission diagnosis of septic shock and shock was controlled. DBP was measured every 1 hour, and the mean DBP during the first 24h (mDBP24h) was recorded. The primary outcome was mortality at 28 days. Multivariable logistic regression determined the relationship between mDBP24h and mortality at 28 days. Results: In total, 1251 patients were finally included. The 28 day mortality of included septic shock patients was 28.3%. The mDBP24h, not mSBP24h,was higher among 28 day survivors compared with non-survivors. 28 day mortality was inversely associated with mDBP24h (unadjusted OR 0.814 per 10mmHg higher mDBP24h, p=0.003), with a stepwise increase in 28 day mortality at lower mDBP24h. The 28 day mortality of patients with mDBP24h <59 mmHg had an absolute risk reduction of 9.4% (p=0.001). And mDBP24h<59mmHg was the remaining high risk factor inversely associated with 28 day mortality after multivariable adjustment (adjusted OR 1.915, 95% CI 1.037-3.536, p=0.038), while mMAP24h and mSBP24h were not. Conclusion: In patients with septic shock after initial resuscitation, we observed an inverse relationship between mDBP24h and 28 day mortality. The poor outcomes in patients with mDBP24h<59mmHg provide indirect evidence supporting a further DBP goal of 59 mmHg for patients with septic shock after MAP of 65mmHg was achieved.
... Intensive fluid resuscitation is essential for patients in hemorrhagic shock after trauma, however, it can lead to fluid overload, which in consequence, can worsen the condition and lead to serious complications, including pulmonary edema, cardiac failure, delayed wound healing, tissue breakdown and impaired bowel function. Endothelial glycocalyx shading and increased vascular permeability caused by hemorrhagic shock and systemic inflammatory response syndrome (SIRS) associated with trauma can be further aggravated by aggressive fluid resuscitation (22). Thus, fluid resuscitation should be limited to the minimal necessary volumes and stopped as soon as possible with deresuscitation started immediately after the patient's condition stabilizes. ...
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Background: Appropriate fluid management is essential in the treatment of critically ill trauma patients. Both insufficient and excessive fluid volume can be associated with worse outcomes. Intensive fluid resuscitation is a crucial element of early resuscitation in trauma; however, excessive fluid infusion may lead to fluid accumulation and consequent complications such as pulmonary edema, cardiac failure, impaired bowel function, and delayed wound healing. The aim of this study was to examine the volumes of fluids infused in critically ill trauma patients during the first hours and days of treatment and their relationship to survival and outcomes. Methods: We retrospectively screened records of all consecutive patients admitted to the intensive care unit (ICU) from the beginning of 2019 to the end of 2020. All adults who were admitted to ICU after trauma and were hospitalized for a minimum of 2 days were included in the study. We used multivariate regression analysis models to assess a relationship between volume of infused fluid or fluid balance, age, ISS or APACHE II score, and mortality. We also compared volumes of fluids in survivors and non-survivors including additional analyses in subgroups depending on disease severity (ISS score, APACHE II score), blood loss, and age. Results: A total of 52 patients met the inclusion criteria for the study. The volume of infused fluids and fluid balance were positively correlated with mortality, complication rate, time on mechanical ventilation, length of stay in the ICU, INR, and APTT. Fluid volumes were significantly higher in non-survivors than in survivors at the end of the second day of ICU stay (2.77 vs. 2.14 ml/kg/h) and non-survivors had a highly positive fluid balance (6.21 compared with 2.48 L in survivors). Conclusion: In critically ill trauma patients, worse outcomes were associated with higher volumes of infusion fluids and a more positive fluid balance. Although fluid resuscitation is lifesaving, especially in the first hours after trauma, fluid infusion should be limited to a necessary minimum to avoid fluid overload and its negative consequences.