Microcirculatory Perfusion Research Articles

Early and concomitant administration of norepinephrine and ilomedin improves microcirculatory perfusion without impairing macrocirculation in an intestinal ischemia-reperfusion injury swine model : a randomized experimental trial.

Intestinal ischemia-reperfusion injury is associated with both macrocirculatory and microcirculatory failure. Association of a vasoconstrictor in combination with a vasodilator such as ilomedin may improve macrocirculation parameters, microcirculation perfusion and reduce endothelial dysfunction. The primary objective was to demonstrate a difference in mean arterial pressure (MAP) after intestinal reperfusion with the concomitant administration of norepinephrine and ilomedin during ischemia compared with traditional hemodynamic treatment strategies (fluid resuscitation and vasopressors only). Secondary objectives were to demonstrate an improvement in peripheral and intestinal microcirculatory perfusion and endothelial dysfunction after intestinal reperfusion using this association. We conducted a randomized preclinical trial in twenty-one large white pigs, in which a 2-hour small bowel ischemia was performed using a segmental mesenteric occlusion model, followed by a 2-hour reperfusion. Pigs were randomized into 3 groups: goal directed fluid therapy, early administration of norepinephrine before reperfusion and early administration of ilomedin and norepinephrine before reperfusion. Macrocirculatory (MAP and Cardiac Index (CI)), microcirculatory (Sublingual with SideStream Dark Field system and intestinal hemoglobin oxygen saturation with hyperspectral imaging (HSI)) measurements and biological analysis (biomarkers of endothelial dysfunction) were performed. There were no significant differences in the MAP (p = 0.499) and the CI (p = 0.659) between the 3 groups. Perfused Vessel Density (PVD) in sublingual microcirculation was significantly higher immediately after reperfusion and 2 hours after reperfusion in the early administration of ilomedin and norepinephrine group compared with the other 2 groups (p < 0.05). Hemoglobin oxygen saturation measured at the intestinal level was significantly higher immediately after reperfusion in the early administration of ilomedin and norepinephrine group compared with the other 2 groups (p < 0.01). There were no significant differences in biomarkers of endothelial dysfunction between the 3 groups. Creatinine, AST and alkaline phosphatases increased significantly 2 hours after reperfusion in the early administration of ilomedin and norepinephrine group compared with baseline (p < 0.05). Early administration of norepinephrine and ilomedin during ischemia improved short-term post-reperfusion sublingual and intestinal microcirculation without worsening macrocirculatory parameters in an intestinal ischemia-reperfusion injury model. However, use of this strategy seemed to worsen both liver and kidney function.

Evaluation of wound temperature monitoring at various anatomical sites in the management of patients with diabetic foot undergoing microcirculation reconstruction

ObjectiveThis study aims to assess the significance of monitoring temperature change trends at various wound sites in the healing process of diabetic foot ulcers after microcirculation reconstruction surgery.MethodsA retrospective analysis was conducted on individuals with diabetic foot ulcers who had been admitted to the Department of Orthopedics at the Second Hospital of Shanxi Medical University between July 2020 and February 2022. Temperature changes were regularly monitored at the center of the wound and the distal tibia of the ipsilateral lower leg to assess microcirculatory blood perfusion. Wound, ischemia, and foot infection (WIFi) grading was performed at admission and the final follow-up was to determine the value of temperature monitoring at various sites. Additionally, the formation of collateral microarterial vessels was monitored to determine their consistency with the observed trends in temperature differences. Follow-up assessments included the recurrence of ulcers, development of ulcers at different locations, re-amputation of the toe or limb, and diabetes-related mortality.ResultsA total of 29 patients were included in the follow-up, with an average age of 57.14 ± 14.75 years and a follow-up period of 9.79 ± 4.13 months. Following microcirculation reconstruction surgery, as the microvascular network formed, the temperature difference between the center of the wound and the distal tibia on the same side gradually decreased, with no statistical difference observed at 4 weeks postoperatively. At both admission and the final follow-up, there was a significant reduction in the wound (W) and ischemia (I) grades within the WIFi classification. The temperature at the wound center showed progressive improvement as collateral microarterial vessels developed. During the follow-up period, there were 2 cases of ulcer recurrence, 1 case of an ulcer appearing at a different location, no cases of re-amputation of the toe or limb, and 2 diabetes-related fatalities.ConclusionSkin temperature monitoring offers a direct and reliable indication of microcirculatory blood perfusion. Its simplicity and cost-effectiveness make it a valuable tool for widespread use in evaluating wound healing following microcirculation reconstruction surgery.

Hemoadsorption improves kidney microcirculatory oxygenation and oxygen consumption, ameliorates tubular injury, and improves kidney function in a rat model of sepsis-induced AKI

Microcirculatory dysfunction, hypoxia, and inflammation are considered to be central in the pathogenesis of sepsis-induced acute kidney injury (AKI). In this experimental study, we hypothesized that extracorporeal removal of inflammatory cytokines by hemoadsorption (HA) therapy may mitigate renal injury associated with sepsis-induced AKI. To this end, we investigated renal microcirculatory oxygenation and perfusion, oxygen consumption, lactate, systemic hemodynamic variables, tubular cell integrity, inflammatory mediators, and kidney function in a rat model of septic AKI elicited by endotoxin infusion. Three groups of rats were investigated on extracorporeal circulation: HA only, LPS, and LPS + HA. Endotoxin infusion reduced cortex microcirculatory oxygenation and raised creatinine and lactate levels. Renal microcirculatory oxygenation, measured by two independent techniques (phosphorescence (µPO2) and spectrophotometry/Doppler (µHbO2sat and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mu \ ext{RBCv}$$\\end{document})), was ameliorated by HA therapy. The renal oxygen consumption, lactate and creatinine levels were restored in the LPS + HA group. A reduced amount of injured tubular cells was found in histological analysis of the kidneys. This experimental study demonstrated an improvement in multiple determinants of kidney oxygenation, damage, and systemic blood perfusion by HA in a clinically relevant rat model of septic AKI. Further studies are needed to optimize and support the clinical use of HA as a renal protective strategy.

Pretreatment with dual antiplatelet therapy in acute myocardial infarction

Abstract Background Combined antithrombotic therapy prevents thrombus progression and its components embolization, and thus, it has an essential role in coronary microcirculation (re)perfusion in acute myocardial infarction (AMI). Pretreatment with P2Y12 inhibitors, on top of aspirin, before primary angioplasty has not been satisfactorily studied in STEMI. Purpose To investigate the impact of combined antiplatelet therapy on-treatment on the outcome of patients with STEMI. Methods Patients who suffered STEMI during the 7 years (1/2016-12/2022) were included. The analysis is based on population data from the National Health Information System (NHIS). Information on AMIs from the Intervention Module of the Registry of Cardiovascular Operations and Interventions was combined with prescription data from the Registry of Reimbursed Health Services 6 months before MI and identification of deceased patients from the Registry of Death Records. Data from the NHIS covers almost 100% of all cases in the population. Standard descriptive statistics and test were applied in the analysis. Multivariate logistic regression adjusted for clinical and procedural characteristics was adopted to analyze the influence of pretreatment on the risk of 1) out-of-hospital cardiac arrest (OHCA), 2) clinical condition at admission – need of mechanical ventilation and circulatory instability (Killip III,IV), 3) initial TIMI flow through the infarct-related coronary artery (IRA ), and 4) short term mortality. Results The study sample consisted of data from 40,383 STEMIs of which 1,601 patients were on dual antiplatelet therapy (DAPT) with aspirin plus iP2Y12 lasting 1 to 6 months before the event occurred. Patients on chronic oral anticoagulation (N 2101) were excluded. Patients on DAPT versus those without antiplatelet therapy or on aspirin at a daily dose of 100 mg were older, had higher comorbidity rates, and were at higher risk of mortality (Table). The multivariate logistic regression analysis showed that patients on DAPT at the time of MI onset and lasting for at least one month had a higher likelihood of preserved perfusion through the IRA (Odds ratio and 95% Confidence interval, OR (95% CI) 1. 193 (1.074; 1.326), p=0.001). However, the DAPT pretreatment did not reduce the risk of OHCA, the need for mechanical ventilation, or initial circulatory destabilization. It did not positively affect the prognosis of the patients (Figure ). Conclusion The significant benefit of the DAPT pretreatment on the preservation of infarct-related coronary artery flow did not translate into a positive effect on the prognosis of STEMI patients.

To evaluate coronary microvascular obstruction by myocardial contrast echocardiography and its influence on prognosis in patients with ST-segment elevation myocardial infarction

Abstract Background The goal of primary PCI (pPCI) is not only to restore epicardial coronary blood flow quickly but also to provide continuous myocardial tissue level reperfusion through coronary microcirculation. However, the incidence of coronary microvascular obstruction (MVO) after pPCI is as high as 50%-60%, which is closely related to the occurrence of heart failure and increased mortality of patients. Myocardial contrast echocardiography (MCE) is a new noninvasive technique for real-time observation of myocardial microcirculation perfusion in a specific imaging mode. At present, there are few studies on the application of MCE in the evaluation of coronary MVO in STEMI patients in China. Purpose To evaluate coronary MVO by MCE and its influencing factors and prognosis value after pPCI in patients with STEMI. Methods Patients with STEMI who received pPCI from October 2020 to June 2023 in the CCU were enrolled. MCE examination was performed on the 5th to 7th day after pPCI. The patients were divided into the MVO group and Non-MVO group. Major adverse cardiovascular events (MACE) were observed by 6-month follow-up after STEMI onset. Multiple Logistic regression analysis was used to analyze the risk factors for MVO, Multiple Cox regression analysis of the risk factors for MACE and Kaplan-Meier survival curve to compare the cumulative event-free survival of the two groups. Results A total of 98 patients were included in the analysis. The age was 59.88±11.71 years old, and 76(77.55%) were male. MCE examination showed 52 cases in the MVO group and 46 cases in the Non-MVO group. The incidence of MVO was 53.1% (52/98). There were 15 patients with MACE during follow-up. The results of stepwise Multivariate Logistic regression analysis showed that the peak value of cardiac troponin T (cTnT) (OR=1.354,95%CI 1.103-1.661, P=0.004) and without thrombus aspiration (TA) were independent risk factors for MVO (OR=5.588,95%CI 1.915-16.308, P=0.002). Multivariate Cox regression analysis indicated that female (HR=2.891, 95%CI 1.027-8.135, P=0.044), left ventricular ejection fraction (LVEF) &amp;lt;40% (HR=9.960, 95%CI 3.370-29.435, P&amp;lt;0.001) and MVO (HR=5.759,95%CI 1.279-25.935, P=0.023) were independent risk factors for MACE. Kaplan-Meier survival curve showed that the cumulative event-free survival rate in the Non-MVO group was higher than that in the MVO group, and the difference was statistically significant (P=0.0047). Conclusion The incidence of coronary MVO was higher in STEMI patients after pPCI, the peak value of cTnT and without TA were independent risk factors of MVO. The independent risk factors for MACE were female, LVEF &amp;lt; 40%, and MVO.

Sublingual microcirculatory assessment on admission independently predicts the outcome of old intensive care patients suffering from shock

Shock is a life-threatening condition. This study evaluated if sublingual microcirculatory perfusion on admission is associated with 30-day mortality in older intensive care unit (ICU) shock patients. This trial prospectively recruited ICU patients (≥ 80 years old) with arterial lactate above 2 mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of shock cause. All patients received sequential sublingual measurements on ICU admission (± 4 h) and 24 (± 4) hours later. The primary endpoint was 30-day mortality. From September 4th, 2022, to May 30th, 2023, 271 patients were screened, and 44 included. Patients were categorized based on the median percentage of perfused small vessels (sPPV) into those with impaired and sustained microcirculation. 71% of videos were of good or acceptable quality without safety issues. Patients with impaired microcirculation had significantly shorter ICU and hospital stays (p = 0.015 and p = 0.019) and higher 30-day mortality (90.0% vs. 62.5%, p = 0.036). Cox regression confirmed the independent association of impaired microcirculation with 30-day mortality (adjusted hazard ratio 3.245 (95% CI 1.178 to 8.943, p = 0.023). Measuring sublingual microcirculation in critically ill older patients with shock on ICU admission is safe, feasible, and provides independent prognostic information about outcomes.Trial registration NCT04169204.

Predictive value of myocardial contrast echocardiography in evaluating myocardial perfusion and prognosis after percutaneous coronary intervention in patients with acute myocardial infarction

Objective: To evaluate myocardial microcirculation perfusion with myocardial contrast echocardiography (MCE) in patients with acute myocardial infarction after percutaneous coronary intervention (PCI), and to explore the prognostic value of different types of myocardial microcirculation perfusion. Methods: This is a prospective cohort study. Patients with acute myocardial infarction who underwent successful PCI in Nanfang Hospital of Southern Medical University and Kanghua Hospital of Dongguan City from October 2019 to June 2021 were selected. All the enrolled patients completed MCE examination within 72 hours after PCI. According to the examination results, the patients were divided into normal microcirculation perfusion group, delayed microcirculation perfusion group, and blocked microcirculation perfusion group. Adverse cardiovascular events including all-cause death, cardiovascular death, and angina re-hospitalization were followed up, and left ventricular ejection fraction (LVEF) review results were collected at six months to one year after surgery. Kaplan-Meier survival curve was used to investigate the difference in the incidence of adverse cardiovascular events in different myocardial perfusion groups, and Cox regression analysis was used to evaluate the effect of myocardial perfusion on adverse cardiovascular events. Results: A total of 113 patients with acute myocardial infarction were included, aged (56.3±11.5) years, with 88(78%) males. There were 31 cases in the normal microcirculation perfusion group, 43 cases in the delayed microcirculation perfusion group and 39 cases in the blocked microcirculation perfusion group. LVEF was reviewed in 49 patients, and LVEF in the delayed microcirculation perfusion group was significantly improved compared with baseline at follow-up ((63.3±1.2) % vs. (58.6±1.8) %, P=0.043), and there was no statistically significant difference between the other two groups (all P>0.05). The median follow-up time was 473 days, during follow-up period 30 adverse cardiovascular events occurred. Kaplan-Meier survival curve analysis showed that there was a statistically significant difference in the incidence of adverse cardiovascular events among the three groups (Plog-rank=0.029). Cox regression analysis showed that abnormal microcirculation perfusion (defined as delayed and blocked microcirculation perfusion) was an independent predictor of adverse cardiovascular events in patients with acute myocardial infarction after PCI (HR=1.90, 95%CI1.16-3.12, P=0.011). Conclusions: Microcirculatory perfusion decrease or lost is common in patients with acute myocardial infarction after PCI. Timely restoration of blood flow reconstruction can save heart function when microcirculatory perfusion decreases. Microcirculatory perfusion is a predictor of adverse cardiovascular events in patients with acute myocardial infarction, and patients with poor myocardial perfusion are more likely to experience adverse cardiovascular events.

7484 Pseudohypoglycemia In A Patient With Raynaud’s Phenomenon

Abstract Disclosure: J. Fedorko: None. P. Subarajan: None. A.P. Amblee: None. C.A. Poku: None. Background: The term ‘pseudohypoglycemia’ is used to describe the disparity between actual and measured capillary glucose and clinical presentation. It has been used to describe situations when a patient has the characteristic symptoms of low blood glucose (BG) Whipple’s triad), but the patient’s BG levels are within normal limits. Alternatively, this term can also be used to describe falsely low BG levels on finger-stick (capillary) readings in a patient with normal serum glucose levels and without the characteristic Whipple’s triad. Case: A 55-year-old female with Raynaud’s phenomenon was seen in Endocrine clinic with persistent hypoglycemia noted on finger-stick glucose readings. Her finger-stick glucose reading was 43, and was subsequently given 24 grams of glucose gel. Ten minutes later, a repeat finger stick BG was 44. She had no weakness, tremors, shakiness, vision changes, confusion, seizures, lightheadedness, dizziness, tachycardia, palpitations, nervousness, hunger, paresthesias irritability, confusion, seizures, loss of consciousness, or any other symptoms or signs of hypoglycemia. She had no such previous episodes and her fasting BG ranged from mid-70s to 80, with post-meal BG ranging from 100 to mid-100’s. Her most recent hemoglobin A1c was 5.5. She regularly experiences cyanosis of fingers consistent with Raynaud’s phenomenon, triggered by cold air in winter and air conditioners in summer. She does not take any medications for these episodes. Given the absence of classic Whipple triad and normal BG from peripheral blood draw, the patient’s low finger stick BG readings were attributable to Raynaud’s phenomenon. It is postulated to be secondary to decreased perfusion in the digital microcirculation and increased blood transit time in the fingers, resulting in a local increase in glucose consumption and thus low capillary finger stick BG levels. Simultaneously done serum glucose levels are usually normal. Conclusion: Pseudohypoglycemia can occur in patients with impaired peripheral circulation such as Raynaud’s phenomenon, acrocyanosis, peripheral vascular disease, shock, or with increased glycolysis by blood cells like in leukemia, polycythemia and rare infections like African trypanosomiasis, hyperviscosity syndromes like Waldenstrom’s and monoclonal gammopathy of undetermined significance. In patients with low finger-stick (capillary) glucose levels who do not display Whipple’s triad, and have comorbid conditions that might interfere with the BG reading, it is important for clinicians to recognize the difference between true and pseudohypoglycemia. This can be confirmed with a simultaneously done normal serum glucose level and will prevent unnecessary investigations or excessive treatment. Presentation: 6/3/2024

Cerebral Microcirculation: Progress and Outlook of Laser Doppler Flowmetry in Neurosurgery and Neurointensive Care.

Laser Doppler flowmetry (LDF) is a well-established technique for the investigation of tissue microcirculation. Compared to skin, the use in the human brain is sparse. The measurement of cerebral microcirculation in neurointensive care and during neurosurgery is challenging and requires adaptation to the respective clinical setting. The aim of the review is to present state of the art and progress in neurosurgery and neurointensive care where LDF has proven useful and can find clinical importance in the investigation of cerebral microcirculation. The literature in the field is summarized and recent technical improvements regarding LDF systems and fiber optical probe designs for neurosurgical and neurocritical care described. By combining two signals from the LDF unit, the measurement of the microcirculation (Perfusion) and gray whiteness (TLI) of the brain tissue, the full potential of the device is achieved. For example, a forward-looking LDF-probe detects high-risk hemorrhage areas and gray-white matter boundaries along intraoperative trajectories during stereotactic neurosurgery. Proof of principles are given for LDF as a guidance tool in deep brain stimulation implantation, brain tumor needle biopsies, and as long-term monitoring device in neurocritical care. With well-designed fiber optical probes, surgical fixation, and signal processing for movement reduction, LDF monitoring of the cerebral microcirculation is successful up to 10 days. The use of LDF can be combined with other physiological measurement techniques, for example, fluorescence spectroscopy for identification of glioblastoma during tumor surgery. Fiber optics can also be used during magnetic resonance imaging (MRI). Despite the many advantages, fiber optical LDF has not yet reached its full potential in clinical neuro-applications. Multicenter studies are required to further evaluate LDF in neurosurgery and neurointensive care. In conclusion, the present status of LDF in neurosurgery and neurointensive care has been reviewed. By combining Perfusion and TLI with tailored probe designs the full potential of LDF can be achived in measuring cerebral microcirculation. This includes guidance during DBS implantation and needle biopsies, and long-term monitoring in neurocritical care.

Quantitative evaluation of myocardial perfusion in coronary heart disease by myocardial contrast and dobutamine stress echocardiography

AbstractObjectiveWe aimed to investigate how combining myocardial contrast echocardiography (MCE) with dobutamine stress echocardiography (DSE) could help evaluate myocardial perfusion in coronary heart disease patients and understand changes in microcirculation across different levels of coronary artery blockage.MethodsWe conducted MCE and DSE tests on 53 coronary heart disease patients, categorizing ischemic myocardium into four groups: A (&lt;50%), B (50%–69%), C (70%–89%), and D (≥90%). Dynamic myocardial perfusion images were captured during rest and peak dobutamine stress from various angles, analyzing parameters like plateau value A, slope β, and the product A × β, reflecting different aspects of myocardial blood flow.ResultsParametric values of myocardial perfusion (PVMPs) were significantly lower in group D at rest compared with other groups (p &lt; 0.001). PVMPs increased notably at peak dobutamine stress in groups A, B, and C (p &lt; 0.001). Groups A and B had higher PVMPs than groups C and D, with group D significantly lower (p &lt; 0.001). β reserve values decreased gradually from group A to D, with significantly lower values of A and A × β in groups C and D compared with A and B (p &lt; 0.001). Sensitivity and specificity for predicting &gt;70% coronary artery blockage was 80%, 66%, and 74%, 80%, respectively, using specific thresholds.ConclusionCombining MCE with DSE is highly sensitive and accurate in diagnosing obstructive coronary artery blockages. It also helps assess myocardial microcirculation perfusion and left ventricular reserve function, which decline with increasing severity of coronary artery blockage.

Pycnogenol® relieves chronic venous insufficiency (CVI) in diabetics: a supplement registry study.

The aim of this supplement registry study was to evaluate the efficacy of Pycnogenol® in controlling signs and symptoms of chronic venous insufficiency (CVI), diabetic microangiopathy and microcirculatory parameters - in diabetic patients with CVI and microangiopathy. These CVI patients are eligible for medical procedures as their incompetent superficial veins can be treated with repeated sclerotherapy and or local surgery according to needs. During this registry study, only non-interventional managements were used. The effects of the use of elastic compression with standard management (SM) was compared to Pycnogenol® intake (150 mg/day) and SM, without using elastic compression for 8 weeks. Fifty-eight diabetic patients with CVI completed the study with 28 subjects supplemented with Pycnogenol® and 30 in the control group. The two groups completing 8 weeks were comparable at baseline. After 8 weeks, no side effects were observed; the compliance was optimal with >98.5% of the supplement capsules correctly used. The tolerability to stockings was lower (73% of stockings were not fully used for the whole day). There were no dropouts. Venous pressures were comparable in the two groups at baseline. Microcirculatory and clinical measurements of the patients were comparable at inclusion. After 8 weeks, the differences between Pycnogenol® and elastic compression were statistically significant for skin resting flux (RF), rate of ankle swelling (RAS), transcutaneous PO<inf>2</inf> and PCO<inf>2</inf> indicating a significant improvement in microcirculatory perfusion with Pycnogenol® in comparison with elastic compression. In parallel, clinical symptoms assessed by the Composite Symptom Score (CSS), the venous Clinical severity Score (VCSS) and the Venous Disability Score (VDS), were significantly lower in the Pycnogenol® group than in the compression group, indicating a significant clinical effect of Pycnogenol® compared to elastic compression (P<0.05). Pycnogenol® showed important antioxidant properties and lowered oxidative stress as seen also in previous studies. This registry study confirms the clinical and microcirculatory efficacy of Pycnogenol® in CVI in diabetics. The study indicates the significant supplementary, clinical role of Pycnogenol® in the management of this common clinical condition over a short period of time, possibly preventing ulcerations.

Lactated Ringers, albumin and mannitol as priming during cardiopulmonary bypass reduces pulmonary edema in rats compared with hydroxyethyl starch

BackgroundEndothelial disorders with edema formation and microcirculatory perfusion disturbances are common in cardiac surgery with cardiopulmonary bypass (CPB) and contribute to disturbed tissue oxygenation resulting in organ dysfunction. Albumin is protective for the endothelium and could be a useful additive to CPB circuit priming. Therefore, this study aimed to compare organ edema and microcirculatory perfusion in rats on CPB primed with lactated Ringers, albumin and mannitol (LR/albumin/mannitol) compared to 6% hydroxyethyl starch (HES).ResultsMale rats were subjected to 75 min of CPB primed with either LR/albumin/mannitol or with 6% HES. Renal and lung edema were determined by wet/dry weight ratio. Pulmonary wet/dry weight ratio was lower in rats on CPB primed with LR/albumin/mannitol compared to HES (4.77 [4.44–5.25] vs. 5.33 [5.06–6.33], p = 0.032), whereas renal wet/dry weight ratio did not differ between groups (4.57 [4.41–4.75] vs. 4.51 [4.47–4.73], p = 0.813). Cremaster microcirculatory perfusion was assessed before, during and after CPB with intravital microscopy. CPB immediately impaired microcirculatory perfusion compared to baseline (LR/albumin/mannitol: 2 [1–7] vs. 14 [12–16] vessels per recording, p = 0.008; HES: 4 [2–6] vs. 12 [10–13] vessels per recording, p = 0.037), which persisted after weaning from CPB without differences between groups (LR/albumin/mannitol: 5 [1–9] vs. HES: 1 [0–4], p = 0.926). In addition, rats on CPB primed with LR/albumin/mannitol required less fluids to reach sufficient flow rates (0.5 [0.0–5.0] mL vs. 9 [4.5–10.0], p < 0.001) and phenylephrine (20 [0–40] µg vs. 90 [40–200], p = 0.004). Circulating markers for inflammation (interleukin 6 and 10), adhesion (ICAM-1), glycocalyx shedding (syndecan-1) and renal injury (NGAL) were determined by ELISA or Luminex. Circulating interleukin-6 (16 [13–25] vs. 33 [24–51] ng/mL, p = 0.006), interleukin-10 (434 [295–782] vs. 2120 [1309–3408] pg/ml, p < 0.0001), syndecan-1 (5 [3–7] vs. 15 [11–16] ng/mL, p < 0.001) and NGAL (555 [375–1078] vs. 2200 [835–3671] ng/mL, p = 0.008) were lower in rats on CPB primed with LR/albumin/mannitol compared to HES.ConclusionCPB priming with LR, albumin and mannitol resulted in less pulmonary edema, renal injury, inflammation and glycocalyx degradation compared to 6% HES. Furthermore, it enhanced hemodynamic stability compared with HES. Further research is needed to explore the specific role of albumin as a beneficial additive in CPB priming.

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Dual-energy computed tomography iodine quantification combined with laboratory data for predicting microvascular invasion in hepatocellular carcinoma: a two-centre study.

Microvascular invasion (MVI) is a recognized biomarker associated with poorer prognosis in patients with hepatocellular carcinoma. Dual-energy computed tomography (DECT) is a highly sensitive technique that can determine the iodine concentration (IC) in tumour and provide an indirect evaluation of internal microcirculatory perfusion. This study aimed to assess whether the combination of DECT with laboratory data can improve preoperative MVI prediction. This retrospective study enrolled 119 patients who underwent DECT liver angiography at 2 medical centres preoperatively. To compare DECT parameters and laboratory findings between MVI-negative and MVI-positive groups, Mann-Whitney U test was used. Additionally, principal component analysis (PCA) was conducted to determine fundamental components. Mann-Whitney U test was applied to determine whether the principal component (PC) scores varied across MVI groups. Finally, a general linear classifier was used to assess the classification ability of each PC score. Significant differences were noted (P < .05) in alpha-fetoprotein (AFP) level, normalized arterial phase IC, and normalized portal phase IC between the MVI groups in the primary and validation datasets. The PC1-PC4 accounted for 67.9% of the variance in the primary dataset, with loadings of 24.1%, 16%, 15.4%, and 12.4%, respectively. In both primary and validation datasets, PC3 and PC4 were significantly different across MVI groups, with area under the curve values of 0.8410 and 0.8373, respectively. The recombination of DECT IC and laboratory features based on varying factor loadings can well predict MVI preoperatively. Utilizing PCA, the amalgamation of DECT IC and laboratory features, considering diverse factor loadings, showed substantial promise in accurately classifying MVI. There have been limited endeavours to establish such a combination, offering a novel paradigm for comprehending data in related research endeavours.

Machine Learning-Assisted Analysis of Sublingual Microcirculatory Dysfunction for Early Cardiovascular Risk Evaluation and Cardiovascular-Kidney-Metabolic Syndrome Stage in Patients With Type 2 Diabetes Mellitus.

To examine whether sublingual microcirculation can be used as an effective and noninvasive method for assessing cardiovascular, kidney, and metabolic risks in patients with type 2 diabetes mellitus (T2DM). This cross-sectional observational study enrolled 186 patients with T2DM. All patients were evaluated using the Framingham General Cardiovascular Risk Score (FGCRS) and cardiovascular-kidney-metabolic (CKM) syndrome stage. Side-stream dark-field microscopy was used for sublingual microcirculation, including total and perfused vessel density (TVD and PVD). Multiple machine-learning prediction models have been developed for CKM risk and stage assessment in T2DM patients. Receiver operating characteristic (ROC) curves were generated to determine cutoff points. Compared to patients with T2DM, diabetic patients with subclinical atherosclerosis (SA) had a greater CV risk, as measured by the FGCRS, accompanied by markedly decreased microcirculation perfusion. Microcirculatory parameters (TVD and PVD), including carotid intima-media thickness (IMT), brachial-ankle pulse wave velocity (ba-PWV), and FGCRS, were closely associated with SA incidence. Microcirculatory parameters, Index (DMSA screen), and cut-off points were used to screen for SA in patients with T2DM. Furthermore, a new set of four factors identified through machine learning showed optimal sensitivity and specificity for detecting CKM risk in patients with T2DM. Decreased microcirculatory perfusion served as a useful early marker for CKM syndrome risk stratification in patients with T2DM without SA. Sublingual microcirculatory dysfunction is closely correlated with the risk of SA and CKM risk in T2DM patients. Sublingual microcirculation could be a novel tool for assessing the CKM syndrome stage in patients with T2DM.

Shenfu injection ameliorates endotoxemia-associated endothelial dysfunction and organ injury via inhibiting PI3K/Akt-mediated glycolysis

Ethnopharmacological relevanceMicrocirculatory dysfunction is one of the main characteristics of sepsis. Shenfu Injection (SFI) as a traditional Chinese medicine is widely applied in clinical severe conditions. Recent studies have shown that SFI has the ability to ameliorate sepsis-induced inflammation and to improve microcirculation perfusion. Aim of the studyThis study aims to investigate the underlying mechanism of SFI for ameliorating sepsis-associated endothelial dysfunction and organ injury. Materials and methodsSide-stream dark-field (SDF) imaging was used to monitor the sublingual microcirculation of septic patients treated with or without SFI. Septic mouse model was used to evaluate the effects of SFI in vivo. Metabolomics and transcriptomics were performed on endothelial cells to identify the underlying mechanism for SFI-related protective effect on endothelial cells. ResultsSFI effectively abolished the disturbance and loss of sublingual microcirculation in septic patients. Twenty septic shock patients with or without SFI administration were enrolled and the data showed that SFI significantly improved the levels of total vessel density (TVD), perfused vessel density (PVD), microvascular flow index (MFI), and the proportion of perfused vessels (PPV). The administration of SFI significantly decreased the elevated plasma levels of Angiopoietin-2 (Ang2) and Syndecan-1, which are biomarkers indicative of endothelial damage in sepsis patients. In the mouse septic model in vivo, SFI inhibited the upregulation of endothelial adhesion molecules and Ly6G + neutrophil infiltration while restored the expression of VE-Cadherin in the vasculature of the lung, kidney, and liver tissue. Additionally, SFI reduced the plasma levels of Ang2, Monocyte Chemoattractant Protein-1(MCP1), and Interleukin-6 (IL6), and alleviated liver and kidney injury in septic mice. Moreover, SFI significantly inhibited the inflammatory activation and increased permeability of endothelial cells induced by endotoxins in vitro. By performing metabolomics and transcriptomics, we identified the activation of PI3K/Akt-mediated glycolysis as the underlying mechanism for SFI-related protective effect on endothelial cells. ConclusionsOur findings revealed that SFI may improve microcirculation perfusion and endothelial function in sepsis via inhibiting PI3K/Akt-mediated glycolysis, providing theoretical evidence for the clinical application of SFI.

THE ROLE OF GLYCOCALYX IN THE PATHOGENESIS OF DIABETES MELLITUS COMPLICATIONS

Glycocalyx (GC) is represented by protein-polysaccharide compounds lining the inner surface of endothelial cells in the form of a gel. GC plays an important role in the regulation of vascular homeostasis, controls vascular wall permeability and microvascular tone, prevents microvascular thrombosis and participates in the regulation of leukocyte adhesion. Damage of endothelial HA is a part and initial link of pathophysiological processes underlying the development of complications of diabetes mellitus (DM). In most cases of DM is accompanied by degradation of HA caused by hyperglycemia, which leads to impaired microcirculatory perfusion and organ dysfunction. Further study of HA, determination of its contribution to the development of diabetes complications is a very promising area of research. In this review, we analyze the main mechanisms of destruction and the role of HA in the pathophysiological mechanisms of the development of DM complications. Although numerous studies indicate a significant role of HA dysfunction in the development of micro- and macroangiopathies in the outcome of diabetes, many aspects of pathophysiological processes are still unexplored and require further research.

Intracoronary thrombolysis in ST-elevation myocardial infarction: a systematic review and meta-analysis

BackgroundDespite restoration of epicardial blood flow in acute ST-elevation myocardial infarction (STEMI), inadequate microcirculatory perfusion is common and portends a poor prognosis. Intracoronary (IC) thrombolytic therapy can reduce microvascular thrombotic...

Effects of sodium-glucose transporter-2 inhibition on systemic hemodynamics, renal function, and intra-renal oxygenation in sepsis-associated acute kidney injury

BackgroundPeople with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI.MethodsSixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8).ResultsEmpagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes.ConclusionIn a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.

Improvements in edema and microcirculation in chronic venous insufficiency with Pycnogenol® or elastic compression.

Chronic venous insufficiency (CVI) is the consequence of venous valve reflux and/or venous flow obstruction and resulting venous hypertension in the lower extremities. The aim of this prospective supplement registry study was to evaluate the efficacy of compression stockings or Pycnogenol® in controlling symptoms and edema in CVI and their efficacy on microcirculatory parameters. Two comparable groups of 30 subjects with CVI were observed for 4 months. Elastic compression was less tolerated than Pycnogenol® with 12 subjects being unable to follow the compression routine. No side effects due to supplementation were observed; tolerability of the supplementation was optimal. Ambulatory venous pressure (AVP) and refilling time (RT) at inclusion indicated a significant increase in venous pressure and reflux (refilling time <16 seconds). AVP and RT did not change after 4 months. Microcirculatory and clinical measurements were comparable at inclusion between the 2 groups. After 4 months, skin resting flux (RF) and skin PO<inf>2</inf>-PCO<inf>2</inf> were significantly improved with Pycnogenol® compared to compression (P<0.05). The significant increase in skin PO<inf>2</inf> and the decrease in PCO<inf>2</inf> after Pycnogenol® intake were ascribed to the decrease in the abnormally high skin resting flux, a sign of better perfusion and skin nutritional supply. Pycnogenol® reduced leg volume, on average by 18.3% in the evening compared to 4.4% of reduction with compression (P<0.05) showing an important effect on edema. The venous Clinical Severity Score (VCSS) and the composite symptom score (CSS) decreased significantly in the Pycnogenol® group compared to compression, indicating a better improvement in microcirculatory perfusion and nutritional supply produced by the supplementation of Pycnogenol® in comparison with compression. Pycnogenol® significantly improved microcirculation and clinical symptoms in comparison with compression. The decrease in local oxidative stress (OS) at the distal perimalleolar region with Pycnogenol® was significant in comparison with compression (P<0.05). A lower local OS is an important metabolic indication of a better capillary perfusion with better nutritional exchanges. At the end of the registry study, four small ulcerations and skin breaks in four limbs (between 3 and 5 mm of maximum diameters) were observed in the compression group. No ulcerations or skin breaks were observed in the Pycnogenol® group. Pycnogenol® relieved edema, improved microcirculation in CVI patients and reduced stationary, interstitial fluid in comparison with compression. Most symptoms of CVI are associated with interstitial water retention; the presence of extra fluid in limb tissues alters perfusion and nutrient supply. Pycnogenol® supplementation reduced water and fluid accumulation in CVI limbs and improved microcirculation and local oxidative stress thus showing important anti-edema effects.