Publications by authors named "Can Ince"

339 Publications

Cardio-Pulmonary-Renal Consequences of Severe COVID-19.

Cardiorenal Med 2021 Jun 3:1-7. Epub 2021 Jun 3.

Department of Cardiology, Unit Heart Failure, Heart Transplantation & Mechanical Circulatory Support, Thorax Center, Rotterdam, The Netherlands.

Severe acute respiratory syndrome coronavirus 2 has rapidly spread worldwide and resulted in the coronavirus disease 2019 (COVID-19) pandemic. The disease raised an unprecedented demand for intensive care support due to severe pulmonary dysfunction and multiorgan failure. Although the pulmonary system is the potential target of the COVID-19, recent reports have demonstrated that COVID-19 profoundly influences the cardiovascular system and the kidneys. Research studies on cadavers have shown that direct heart and kidney injury can be frequently seen in patients deceased due to COVID-19 infection. On the other hand, functional or structural dysfunction of the heart may deteriorate the renal function and vice versa. This concept is already known as the cardiorenal syndrome and may play a role in COVID-19. Proactive monitoring of micro- and macrohemodynamics could allow prompt correction of circulatory dysfunction and can be of pivotal importance in the prevention of acute kidney injury. Moreover, type and amount of fluid therapy and vasoactive drug support could help manage these patients either with or without mechanical ventilator support. This brief review outlines the current evidence regarding the COVID-19-related renal and cardiorenal complications and discusses potential hemodynamic management strategies.
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http://dx.doi.org/10.1159/000516740DOI Listing
June 2021

Veno-arterial thrombosis and microcirculation imaging in a patient with COVID-19.

Respir Med Case Rep 2021 11;33:101428. Epub 2021 May 11.

Dept. of Intensive Care, Haga Teaching Hospital, The Hague, the Netherlands.

The Coronavirus pandemic has brought new challenges in intensive care medicine. Understanding of the pathophysiology of the vascular complications of SARS-CoV-2 infection could bring new resuscitation and therapeutic options. In this case report, we present a patient with COVID-19 pneumonia, who was admitted to our ICU and treated with high-flow nasal cannula, dexamethasone, remdesivir and high-dose prophylactic low molecular weight heparin. During ICU admission, substantial venous and arterial thrombosis developed. Meanwhile the microcirculation showed more than double amount of organ perfusion with very high total vessel density. We hypothesize that this might be a compensatory mechanism for the generalized prothrombic state in which the microcirculation increases the oxygen extraction capacity preventing multi-organ failure.
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http://dx.doi.org/10.1016/j.rmcr.2021.101428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110328PMC
May 2021

Effect of norepinephrine challenge on cardiovascular determinants assessed using a mathematical model in septic shock: a physiological study.

Ann Transl Med 2021 Apr;9(7):561

Department of Intensive Care, Erasmus MC University Hospital, Rotterdam, The Netherlands.

Background: The present study investigated the cardiovascular determinants of cardiac output (CO), mean systemic filling pressure analogue (Pmsa) derived by Geoffrey Parkin, efficiency of heart (Eh) and related parameters to a norepinephrine (NE) challenge [an increase of 10 mmHg mean arterial pressure (MAP) by NE] in septic shock patients using of a mathematical model.

Methods: Twenty-seven septic shock patients with pulse index continuous cardiac output (PiCCO) monitoring were enrolled. These patients required NE to maintain an individualized MAP for organ perfusion after early fluid resuscitation based on their clinical condition. NE was decreased to obtain a decrease of 10 mmHg from base MAP (MAP), and the NE doses were adjusted to return MAP to baseline (MAP) and produce an increase of 10 mmHg from MAP (MAP). Two NE challenge episodes were analyzed for each patient: from MAP to MAP and from MAP to MAP. The Pmsa, pressure gradient for venous return (PG), and Eh (PGvr relative to Pmsa) were estimated using a mathematical model for the three MAP levels (MAP, MAP and MAP).

Results: A total of 54 episodes of NE challenges were obtained in 27 patients. Significant and consistent increases were observed in the central venous pressure (CVP), Pmsa, and PGvr in response during the NE titration. ΔCO negatively and significantly correlated with ΔCVP (r=-0.722, P<0.0001), ΔPmsa (r=-0.549, P<0.0001), ΔResistance of venous return (Rvr) (r=-0.597, P<0.0001), and ΔResistance of systemic vascular beds (Rsys) (r=-0.597, P<0.0001). Episodes of decreasing CO/Eh were associated with a higher ΔCVP than the CO/Eh-increasing episodes. The area under the curve (AUC) of ΔCVP to predict decreased CO by the incremental NE was 0.86, and the AUC of ΔCVP to predict decreased Eh was 0.94. A cutoff of ΔCVP >1.5 mmHg for detecting decreased CO resulted in a sensitivity of 75% and a specificity of 94.1%. A cutoff of ΔCVP >1.5 mmHg for detecting decreased Eh resulted in a sensitivity of 64.3% and a specificity of 100%.

Conclusions: There were a highly divergent response in Eh and CO to afterload challenge episodes of an NE-induced 10mmHg increase in MAP. An increase in CVP may be an early alarm to identify the reduction in CO/Eh during an NE-induced increase of MAP.
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http://dx.doi.org/10.21037/atm-20-6686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105783PMC
April 2021

Microcirculatory Response to Changes in Venoarterial Extracorporeal Membrane Oxygenation Pump Flow: A Prospective Observational Study.

Front Med (Lausanne) 2021 7;8:649263. Epub 2021 Apr 7.

Department of Anesthesiology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) pump flow is crucial for maintaining organ perfusion in patients with cardiogenic shock, but VA-ECMO pump flow optimization remains as a clinical challenge. This study aimed to investigate the response of sublingual microcirculation to changes in VA-ECMO pump flow. Sublingual microcirculation was measured before and after changing VA-ECMO pump flow according to the treatment plan of ECMO team within 24 h and at 24-48 h after VA-ECMO placement. In clinical events of increasing VA-ECMO pump flow, those events with increased perfused vessel density (PVD) were grouped into group A, and the others were grouped into group B. In clinical events of decreasing VA-ECMO pump flow, those events with increased PVD were grouped into group C, and the others were grouped into group D. Increased PVD was observed in 60% (95% CI, 38.5-81.5%) of the events with increasing VA-ECMO pump flow. The probability of increasing PVD after increasing VA-ECMO pump flow were higher in the events with a PVD < 15 mm/mm at baseline than those with a PVD ≥ 15 mm/mm [100% (95% CI, 54.1-100%) vs. 42.9% (95% CI, 17.7-71.1%), = 0.042]. Other microcirculatory and hemodynamic parameters at baseline did not differ significantly between group A and B or between group C and D. This study revealed contradictory and non-contradictory responses of sublingual microcirculation to changes in VA-ECMO pump flow. Tandem measurements of microcirculation before and after changing VA-ECMO pump flow may help to ensure a good microcirculation.
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http://dx.doi.org/10.3389/fmed.2021.649263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058194PMC
April 2021

Corrections to "Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging: In Vitro and In Vivo Evaluation".

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Jun 25;68(6):2321. Epub 2021 May 25.

In the above article [1], the authors regret that there was a mistake in calculating the mol% of the microbubble coating composition used. For all experiments, the unit in mg/mL was utilized and the conversion mistake only came when converting to mol% in order to define the ratio between the coating formulation components. The correct molecular weight of PEG-40 stearate is 2046.54 g/mol [2], [3], not 328.53 g/mol. On page 556, Table I should read as shown here.
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http://dx.doi.org/10.1109/TUFFC.2021.3067599DOI Listing
June 2021

Case Report: Sublingual Microcirculatory Alterations in a Covid-19 Patient With Subcutaneous Emphysema, Venous Thrombosis, and Pneumomediastinum.

Front Med (Lausanne) 2020 28;7:624695. Epub 2021 Jan 28.

Department of Intensive Care, Haga Teaching Hospital, The Hague, Netherlands.

The Corona virus disease 2019 (Covid-19) has brought a wide range of challenges in intensive care medicine. Understanding of the pathophysiology of Covid-19 relies on interpreting of its impact on the vascular, particularly microcirculatory system. Herein we report on the first use of the latest generation hand-held vital microscope to evaluate the sublingual microcirculation in a Covid-19 patient with subcutaneous emphysema, venous thrombosis and pneumomediastinum. Remarkably, microcirculatory parameters of the patient were increased during the exacerbation period, which is not a usual finding in critically ill patients mostly presenting with a loss of hemodynamic coherence. In contrast, recovery from the disease led to a subsequent amelioration of these parameters. This report clearly shows the importance of microcirculatory monitoring for evaluating the course and the adequacy of therapy in Covid-19 patients.
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http://dx.doi.org/10.3389/fmed.2020.624695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876339PMC
January 2021

Noninvasive, in vivo assessment of the cervical microcirculation using incident dark field imaging.

Microvasc Res 2021 05 9;135:104145. Epub 2021 Feb 9.

Amsterdam UMC, University of Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam Reproduction & Development Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Bergman Clinics, Department of Gynaecology, Bergman Vrouwenzorg, Nijenburg 152, 1081 GG Amsterdam, the Netherlands.

Aim: This study evaluates the feasibility of handheld vital microscopy for noninvasive, objective assessment of the microcirculation of the human uterine cervix. We qualitatively and quantitatively describe the microcirculation in healthy subjects in order to provide a basis for its application in cervical pathology.

Methods: Incident dark field imaging was used to image the microcirculation in four quadrants of the uterine ectocervix in ten healthy participants. If the squamocolumnar junction was visible, measurements were repeated on the endocervical columnar epithelium as well. Image acquisition time was recorded and participants scored the experienced level of discomfort. Angioarchitecture was classified according to Weber's classification. Quantitative parameters included capillary density (CD), total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI).

Results: Image acquisition was easy, fast and well tolerated. Angioarchitecture was characterized by two distinctive and organized patterns; capillary loops underneath the squamous epithelium of the ectocervix and vascular networks underneath the columnar epithelium. In the image sequences containing capillary loops, mean CD was 33.2 cpll/mm (95% CI 28.2-38.2 cpll/mm). In the image sequences with vascular networks, mean TVD was 12.5 mm/mm (95% CI 11.2-13.77 mm/mm), mean PVD was 12.2 (95% CI 11.0-13.5 mm/mm), MFI was 3 and PPV was 100%.

Conclusions: Incident dark field imaging allows for noninvasive, real time visualization and objective evaluation and quantification of the microcirculation of the uterine cervix. The organized vascular patterns and optimal perfusion observed in healthy subjects allow for comparison with cervical pathology, for example in patients with cervical dysplasia or cervical cancer.
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http://dx.doi.org/10.1016/j.mvr.2021.104145DOI Listing
May 2021

Capillary Leukocytes, Microaggregates, and the Response to Hypoxemia in the Microcirculation of Coronavirus Disease 2019 Patients.

Crit Care Med 2021 04;49(4):661-670

Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.1097/CCM.0000000000004862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963442PMC
April 2021

Improved Survival beyond 28 Days up to 1 Year after CytoSorb Treatment for Refractory Septic Shock: A Propensity-Weighted Retrospective Survival Analysis.

Blood Purif 2020 Dec 22:1-7. Epub 2020 Dec 22.

Department of Intensive Care Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background And Aims: It is currently unknown whether CytoSorb treatment for septic shock improves long-term survival beyond 28 days from intensive care unit (ICU) admission and which factors determine outcome.

Methods: This was a long-term follow-up retrospective analysis of patients with septic shock who were treated with continuous renal replacement therapy (CRRT) + CytoSorb (n = 67) or CRRT alone (n = 49). These patients were previously analyzed for 28-day mortality. The primary outcome was the time to long-term all-cause mortality. Factors associated with time to event were analyzed both weighted by stabilized inverse probability of treatment weights (sIPTW) as well as unweighted stratified by therapy received.

Results: The median follow-up for the total cohort was 30 days (interquartile range [IQR]: 5-334, maximum 1,059 days) after ICU admission and 333 days (IQR: 170-583) for those who survived beyond 28 days (n = 59). Survival beyond 28 days was sustained up to 1 year after ICU admission for both treatment regimens: 80% (standard error [SE] 7%) vs. 87% (SE 7%), for CytoSorb vs. CRRT, respectively, p = 0.853. By sIPTW, CytoSorb was significantly associated with long-term outcome compared to CRRT (adjusted hazard ratio [aHR] 0.59, 95% confidence interval [CI] 0.37-0.93, p = 0.025). Independent factors associated with long-term outcome in CytoSorb-treated patients were baseline log10 lactate levels (aHR 5.1, p = 0.002), age in the presence of comorbidity (aHR 2.60, p = 0.013), and presence of abdominal sepsis (aHR 0.34, p = 0.004). A lactate level above 6.0 mmol/L at the start of CytoSorb therapy had a positive predictive value of 79% for mortality (p = 0.013).

Conclusions: Survival is achieved with CytoSorb and CRRT for patients with septic shock beyond 28 days from ICU admission and may be improved for CytoSorb treatment. Lactate levels above 6.0 mmol/L at the start of CytoSorb therapy are predictive of worse outcome with high specificity and positive predictive value.
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http://dx.doi.org/10.1159/000512309DOI Listing
December 2020

The effect of blood transfusion on sublingual microcirculation in critically ill patients: A scoping review.

Microcirculation 2021 04 9;28(3):e12666. Epub 2020 Nov 9.

Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.

Purpose: To investigate the effects of red blood cell (RBC) transfusion on sublingual microcirculation in critically ill patients.

Methods: Systematic strategy was conducted to search studies that measured sublingual microcirculation before and after transfusion in critically ill patients. This review was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Scoping Review Extension.

Results: The literature search yielded 114 articles. A total of 11 studies met the inclusion criteria. Observational evidence showed diffusive capacity of the microcirculation significantly improved in intraoperative and anemic hematologic patients after transfusion, while the convective parameters significantly improved in traumatic patients. RBC transfusion improved both diffusive and convective microcirculatory parameters in hypovolemic hemorrhagic shock patients. Most of the studies enrolled septic patients showed no microcirculatory improvements after transfusion. The positive effects of the leukoreduction were insufficiently supported. The effects of the storage time of the RBCs were not conclusive. The majority of the evidence supported a negative correlation between baseline proportion of perfused vessels (PPV) and changes in PPV.

Conclusions: This scoping review has catalogued evidence that RBC transfusion differently improves sublingual microcirculation in different populations. The existing evidence is not sufficient to conclude the effects of the leukoreduction and storage time of RBCs.
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http://dx.doi.org/10.1111/micc.12666DOI Listing
April 2021

Detection of inadequate anastomotic perfusion with handheld vital microscopy in two patients during colorectal surgery.

Clin J Gastroenterol 2021 Feb 21;14(1):141-145. Epub 2020 Sep 21.

Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands.

Introduction: Anastomotic leakage is one of the most feared complications after gastrointestinal surgery. Assessment of anastomotic viability during surgery remains challenging. Sufficient bowel tissue perfusion is a requisite for anastomotic healing. Handheld vital microscopy (HVM) is a non-invasive technique that can directly visualize the intestinal microcirculation during surgery.

Presentation Of Two Cases: Two patients underwent elective laparoscopic colorectal surgery. During surgery HVM was used to assess bowel perfusion prior to creation of a primary anastomosis. Although the bowel macroscopically appeared to be well perfused, HVM showed a severely compromised microcirculation. The colon was re-internalized and during the following minutes cyanosis of the bowel occurred which was visually determined by the surgeon. After dissection towards cranially, a new site for the primary anastomosis was chosen. The postoperative period was uncomplicated.

Discussion: Sufficient bowel tissue perfusion is often mentioned as key in the pathophysiology of anastomotic leakage. HVM is a technique that could potentially aid surgeons in the assessment of microcirculatory perfusion of the bowel during surgery.

Conclusion: We report two cases undergoing colorectal surgery in which HVM showed merit in detecting compromised bowel perfusion before creation of a primary anastomosis.
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http://dx.doi.org/10.1007/s12328-020-01235-zDOI Listing
February 2021

Automated Algorithm Analysis of Sublingual Microcirculation in an International Multicentral Database Identifies Alterations Associated With Disease and Mechanism of Resuscitation.

Crit Care Med 2020 10;48(10):e864-e875

Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Objectives: Reliable automated handheld vital microscopy image sequence analysis and the identification of disease states and effects of therapy are prerequisites for the routine use of quantitative sublingual microcirculation measurements at the point-of-care. The present study aimed to clinically validate the recently introduced MicroTools software in a large multicentral database of perioperative and critically ill patients and to use this automatic algorithm to data-mine and identify the sublingual microcirculatory variable changes in response to disease and therapy.

Design: Retrospective algorithm-based image analysis and data-mining within a large international database of sublingual capillary microscopy. Algorithm-based analysis was compared with manual analysis for validation. Thereafter, MicroTools was used to identify the functional microcirculatory alterations associated with disease conditions and identify therapeutic options for recruiting functional microcirculatory variables.

Setting: Ten perioperative/ICU/volunteer studies in six international teaching hospitals.

Patients: The database encompass 267 adult and pediatric patients undergoing surgery, treatment for sepsis, and heart failure in the ICU and healthy volunteers.

Interventions: Perioperative and ICU standard of care.

Measurements And Main Results: One thousand five hundred twenty-five handheld vital microscopy image sequences containing 149,257 microscopy images were analyzed. 3.89 × 10 RBC positions were tracked by the algorithm in real time, and offline manual analysis was performed. Good correlation and trending ability were found between manual and automatic total and functional capillary density (r = 0.6-0.8; p < 0.0001). RBC tracking within the database demonstrated changes in functional capillary density and/or RBC velocity in septic shock, heart failure, hypovolemia, obstructive shock, and hemodilution and thus detected the presence of a disease condition. Therapies recruiting the microcirculatory diffusion and convection capacity associated with systemic vasodilation and an increase in cardiac output were separately identified.

Conclusions: Algorithm-based analysis of the sublingual microcirculation closely matched manual analysis across a broad spectrum of populations. It successfully identified a methodology to quantify microcirculatory alterations associated with disease and the success of capillary recruitment, improving point-of-care application of microcirculatory-targeted resuscitation procedures.
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http://dx.doi.org/10.1097/CCM.0000000000004491DOI Listing
October 2020

Novel non-invasive imaging method for baseline risk stratification in cardiac surgery patients.

BMJ Case Rep 2020 Sep 8;13(9). Epub 2020 Sep 8.

Department of Cardiothoracic Surgery, Amsterdam UMC-AMC Campus, Amsterdam, The Netherlands

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http://dx.doi.org/10.1136/bcr-2020-234950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481092PMC
September 2020

Effects of Hemoadsorption with Cytosorb during Severe Rhabdomyolysis: Reply to the Letter to the Editor of Daum and Colleagues.

Blood Purif 2021 3;50(2):273-274. Epub 2020 Sep 3.

Department of Intensive Care, Erasmus Medical Centre, University Medical Center, Rotterdam, The Netherlands.

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http://dx.doi.org/10.1159/000509898DOI Listing
September 2020

Hemodilution causes glycocalyx shedding without affecting vascular endothelial barrier permeability in rats.

J Clin Transl Res 2020 Jun 12;5(5):243-252. Epub 2020 May 12.

Department of Adult Intensive Care, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: The consequences of acute normovolemic hemodilution (ANH) following different types of fluids on the different components of the glycocalyx and on vascular barrier permeability (VBP) remain unknown.

Aim: The aim of the study was to investigate whether the microcirculatory disruption and glycocalyx shedding induced by ANH alters VBP and whether this is affected by the composition and volume of the resuscitation fluid.

Materials And Methods: Anesthetized Wistar albino rats (n=24) underwent stepwise ANH at hematocrit levels of 35%, 25%, 20%, and 15% induced by the exchange of blood with 6% balanced hydroxyethyl starch (1:1), balanced crystalloid (1:3), and normal saline (NS) (1:3). Glycocalyx-shed products were measured at each level of hemodilution. VBP was reflected in the decay of fluorescence dyes of different molecular size and their plasma retention ratios. Edema was assessed by measuring organ water content and muscle microcirculation by hand-held videomicroscopy.

Results: NS caused increased degradation of heparan sulfate and hyaluronan compared with the control group (=0.003, =0.004, respectively). Neither VBP nor tissue edema was affected by the fluid used. The total and perfused vessel densities within the microcirculation of muscle tissue decreased at hematocrit 15% in the balanced crystalloid (=0.02) and NS groups only (<0.0001, =0.0003, respectively) compared with baseline.

Conclusions: Balanced colloid solution preserved the glycocalyx layer better than balanced and unbalanced crystalloid solutions while maintaining the microcirculatory function associated with an improved total intravascular volume. Among the fluids tested, NS caused the most microcirculatory alterations. While ANH caused the degradation of glycocalyx components regardless of fluid, it did not disrupt the vascular barrier as indicated by macromolecular leakage.

Relevance For Patients: The results of this study provide insight into the choice of fluid for optimal perioperative fluid management and the consequences of fluid type on the vascular barrier, glycocalyx, and microcirculation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453805PMC
June 2020

Intraoperative Imaging Techniques to Visualize Hepatic (Micro)Perfusion: An Overview.

Eur Surg Res 2020 13;61(1):2-13. Epub 2020 Jul 13.

Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

The microcirculation plays a crucial role in the distribution of perfusion to organs. Studies have shown that microcirculatory dysfunction is an independent predictor of morbidity and mortality. Hence, assessment of liver perfusion offers valuable information on the (patho)physiological state of the liver. The current review explores techniques in perfusion imaging that can be used intraoperatively. Available modalities include dynamic contrast-enhanced ultrasound, handheld vital microscopes, indocyanine green fluorescence angiography, and laser contrast speckle imaging. Dynamic contrast-enhanced ultrasound relays information on deep tissue perfusion and is a commonly used technique to assess tumor perfusion. Handheld vital microscopes provide direct visualization of the sinusoidal architectural structure of the liver, which is a unique feature of this technique. Intraoperative fluorescence imaging uses indocyanine green, a dye that is administered intravenously to visualize microvascular perfusion when excited using near-infrared light. Laser speckle contrast imaging produces non-contact large surface-based tissue perfusion imaging free from movement- or pressure-related artefacts. In this review, we discuss the intrinsic advantages and disadvantages of these techniques and their clinical and/or scientific applications.
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http://dx.doi.org/10.1159/000508348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592948PMC
July 2020

Assessment of sublingual microcirculation in critically ill patients: consensus and debate.

Ann Transl Med 2020 Jun;8(12):793

Department of Intensive Care Med, Laboratory of Translational Intensive Care Med, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

The main concern in shock and resuscitation is whether the microcirculation can carry adequate oxygen to the tissues and remove waste. Identification of an intact coherence between macro- and microcirculation during states of shock and resuscitation shows a functioning regulatory mechanism. However, loss of hemodynamic coherence between the macro and microcirculation can be encountered frequently in sepsis, cardiogenic shock, or any hemodynamically compromised patient. This loss of hemodynamic coherence results in an improvement in macrohemodynamic parameters following resuscitation without a parallel improvement in microcirculation resulting in tissue hypoxia and tissue compromise. Hand-held vital microscopes (HVMs) can visualize the microcirculation and help to diagnose the nature of microcirculatory shock. Although treatment with the sole aim of recruiting the microcirculation is as yet not realized, interventions can be tailored to the needs of the patient while monitoring sublingual microcirculation. With the help of the newly introduced software, called MicroTools, we believe sublingual microcirculation monitoring and diagnosis will be an essential point-of-care tool in managing shock patients.
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http://dx.doi.org/10.21037/atm.2020.03.222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333125PMC
June 2020

Interpatient heterogeneity in hepatic microvascular blood flow during vascular inflow occlusion (Pringle manoeuvre).

Hepatobiliary Surg Nutr 2020 Jun;9(3):271-283

Department of Surgery, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Background: Vascular inflow occlusion (VIO) during liver resections (Pringle manoeuvre) can be applied to reduce blood loss, however may at the same time, give rise to ischemia-reperfusion injury (IRI). The aim of this study was to assess the characteristics of hepatic microvascular perfusion during VIO in patients undergoing major liver resection.

Methods: Assessment of hepatic microcirculation was performed using a handheld vital microscope (HVM) at the beginning of surgery, end of VIO (20 minutes) and during reperfusion after the termination of VIO. The microcirculatory parameters assessed were: functional capillary density (FCD), microvascular flow index (MFI) and sinusoidal diameter (SinD).

Results: A total of 15 patients underwent VIO; 8 patients showed hepatic microvascular perfusion despite VIO (partial responders) and 7 patients showed complete cessation of hepatic microvascular perfusion (full responders). Functional microvascular parameters and blood flow levels were significantly higher in the partial responders when compared to the full responders during VIO (FCD: 0.84±0.88 . 0.00±0.00 mm/mm, P<0.03, respectively, and MFI: 0.69-0.22 . 0.00±0.00, P<0.01, respectively).

Conclusions: An interpatient heterogeneous response in hepatic microvascular blood flow was observed upon VIO. This may explain why clinical strategies to protect the liver against IRI lacked consistency.
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http://dx.doi.org/10.21037/hbsn.2020.02.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262621PMC
June 2020

Intravenous fluid therapy in the perioperative and critical care setting: Executive summary of the International Fluid Academy (IFA).

Ann Intensive Care 2020 May 24;10(1):64. Epub 2020 May 24.

Department of Intensive Care Medicine, Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg, Antwerp, Belgium.

Intravenous fluid administration should be considered as any other pharmacological prescription. There are three main indications: resuscitation, replacement, and maintenance. Moreover, the impact of fluid administration as drug diluent or to preserve catheter patency, i.e., fluid creep, should also be considered. As for antibiotics, intravenous fluid administration should follow the four Ds: drug, dosing, duration, de-escalation. Among crystalloids, balanced solutions limit acid-base alterations and chloride load and should be preferred, as this likely prevents renal dysfunction. Among colloids, albumin, the only available natural colloid, may have beneficial effects. The last decade has seen growing interest in the potential harms related to fluid overloading. In the perioperative setting, appropriate fluid management that maintains adequate organ perfusion while limiting fluid administration should represent the standard of care. Protocols including a restrictive continuous fluid administration alongside bolus administration to achieve hemodynamic targets have been proposed. A similar approach should be considered also for critically ill patients, in whom increased endothelial permeability makes this strategy more relevant. Active de-escalation protocols may be necessary in a later phase. The R.O.S.E. conceptual model (Resuscitation, Optimization, Stabilization, Evacuation) summarizes accurately a dynamic approach to fluid therapy, maximizing benefits and minimizing harms. Even in specific categories of critically ill patients, i.e., with trauma or burns, fluid therapy should be carefully applied, considering the importance of their specific aims; maintaining peripheral oxygen delivery, while avoiding the consequences of fluid overload.
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http://dx.doi.org/10.1186/s13613-020-00679-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245999PMC
May 2020

Automated quantification of tissue red blood cell perfusion as a new resuscitation target.

Curr Opin Crit Care 2020 06;26(3):273-280

Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Purpose Of Review: Identification of insufficient tissue perfusion is fundamental to recognizing circulatory shock in critically ill patients, and the primary target to restore adequate oxygen delivery. However, the concept of tissue perfusion remains ill-defined and out-of-reach for clinicians as point-of-care resuscitation target. Even though handheld vital microscopy (HVM) provides the technical prerequisites to collect information on tissue perfusion in the sublingual microcirculation, challenges in image analysis prevent quantification of tissue perfusion and manual analysis steps prohibit point-of-care application. The present review aims to discuss recent advances in algorithm-based HVM analysis and the physiological basis of tissue perfusion-based resuscitation parameters.

Recent Findings: Advanced computer vision algorithm such as MicroTools independently quantify microcirculatory diffusion and convection capacity by HVM and provide direct insight into tissue perfusion, leading to our formulation a functional parameter, tissue red blood cell (RBC) perfusion (tRBCp). Its definition is discussed in terms of the physiology of oxygen transport to the tissue and its expected effect as a point-of-care resuscitation target. Further refinements to microcirculatory monitoring include multiwavelength HVM techniques and maximal recruitable microcirculatory diffusion and convection capacity.

Summary: tRBCp as measured using algorithm-based HVM analysis with an automated software called MicroTools, represents a promising candidate to assess microcirculatory delivery of oxygen for microcirculation-based resuscitation in critically ill patients at the point-of-care.
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http://dx.doi.org/10.1097/MCC.0000000000000725DOI Listing
June 2020

Monitoring coherence between the macro and microcirculation in septic shock.

Authors:
Jan Bakker Can Ince

Curr Opin Crit Care 2020 06;26(3):267-272

Department of Intensive Care Adults, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Purpose Of Review: Currently, the treatment of patients with shock is focused on the clinical symptoms of shock. In the early phase, this is usually limited to heart rate, blood pressure, lactate levels and urine output. However, as the ultimate goal of resuscitation is the improvement in microcirculatory perfusion the question is whether these currently used signs of shock and the improvement in these signs actually correspond to the changes in the microcirculation.

Recent Findings: Recent studies have shown that during the development of shock the deterioration in the macrocirculatory parameters are followed by the deterioration of microcirculatory perfusion. However, in many cases the restoration of adequate macrocirculatory parameters is frequently not associated with improvement in microcirculatory perfusion. This relates not only to the cause of shock, where there are some differences between different forms of shock, but also to the type of treatment.

Summary: The improvement in macrohemodynamics during the resuscitation is not consistently followed by subsequent changes in the microcirculation. This may result in both over-resuscitation and under-resuscitation leading to increased morbidity and mortality. In this article the principles of coherence and the monitoring of the microcirculation are reviewed.
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http://dx.doi.org/10.1097/MCC.0000000000000729DOI Listing
June 2020

Resuscitation with PEGylated carboxyhemoglobin preserves renal cortical oxygenation and improves skeletal muscle microcirculatory flow during endotoxemia.

Am J Physiol Renal Physiol 2020 05 13;318(5):F1271-F1283. Epub 2020 Apr 13.

Department of Translational Physiology, Amsterdam University Medical Center Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

PEGylated carboxyhemoglobin (PEGHbCO), which has carbon monoxide-releasing properties and plasma expansion and oxygen-carrying properties, may improve both skeletal microcirculatory flow and renal cortical microcirculatory Po (CµPo) and, subsequently, limit endotoxemia-induced acute kidney injury. Anesthetized, ventilated Wistar albino rats ( = 44) underwent endotoxemic shock. CµPo was measured in exposed kidneys using a phosphorescence-quenching method. Rats were randomly assigned to the following five groups: ) unresuscitated lipopolysaccharide (LPS), ) LPS + Ringer's acetate (RA), ) LPS + RA + 0.5 µg·kg·min norepinephrine (NE), ) LPS + RA + 320 mg/kg PEGHbCO, and ) LPS + RA + PEGHbCO + NE. The total volume was 30 mL/kg in each group. A time control animal group was used. Skeletal muscle microcirculation was assessed by handheld intravital microscopy. Kidney immunohistochemistry and myeloperoxidase-stained leukocytes in glomerular and peritubular areas were analyzed. Endotoxemia-induced histological damage was assessed. Plasma levels of IL-6, heme oxygenase-1, malondialdehyde, and syndecan-1 were assessed by ELISA. CµPo was higher in the LPS + RA + PEGHbCO-resuscitated group, at 35 ± 6mmHg compared with 21 ± 12 mmHg for the LPS+RA group [mean difference: -13.53, 95% confidence interval: (-26.35; -0.7156), = 0.035]. The number of nonflowing, intermittent, or sluggish capillaries was smaller in groups infused with PEGHbCO compared with RA alone ( < 0.05), while the number of normally perfused vessels was greater ( < 0.05). The addition of NE did not further improve CµPo or microcirculatory parameters. Endotoxemia-induced kidney immunohistochemistry and histological alterations were not mitigated by PEGHbCO 1 h after resuscitation. Renal leukocyte infiltration and plasma levels of biomarkers were similar across groups. PEGHbCO enhanced CµPo while restoring skeletal muscle microcirculatory flow in previously nonflowing capillaries. PEGHbCO should be further evaluated as a resuscitation fluid in mid- to long-term models of sepsis-induced acute kidney injury.
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http://dx.doi.org/10.1152/ajprenal.00513.2019DOI Listing
May 2020

Microvascular Dysfunction in the Critically Ill.

Crit Care Clin 2020 Apr 22;36(2):323-331. Epub 2020 Jan 22.

Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street, #611, Little Rock, AR 72212, USA. Electronic address:

Microvascular dysfunction is a frequent complication of many chronic and acute conditions, especially in the critically ill. Moreover, the severity of microvascular alterations is associated with development of organ dysfunction and poor outcome. The complexities and heterogeneity of critical illness, especially in the elderly patient, requires more mechanistically oriented clinical trials that monitor the effectiveness of existing therapies and of those to come. Recent advances in the ability to obtain physiologically based assessments of microcirculatory function at the bedside will make microcirculatory-guided resuscitation a point of care reality.
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http://dx.doi.org/10.1016/j.ccc.2019.11.003DOI Listing
April 2020

Successful Reduction of Creatine Kinase and Myoglobin Levels in Severe Rhabdomyolysis Using Extracorporeal Blood Purification (CytoSorb®).

Blood Purif 2020 28;49(6):743-747. Epub 2020 Feb 28.

Department of Intensive Care, Erasmus Medical Centre, University Medical Center, Rotterdam, The Netherlands.

Rhabdomyolysis, if severe, can lead to acute kidney injury (AKI). Myoglobin is an iron and oxygen-binding protein that is freely filtered by the glomerulus. Precipitation of myoglobin in the nephrons' distal parts is responsible for tubular damage with AKI as a consequence. Extracorporeal clearance of myoglobin is conventionally attempted by the use of continuous renal replacement therapy (CRRT) with high cut-off dialysis membranes to limit the extent of the damage. We describe a case of a 56-year-old man with traumatic crush injury and a persistent source of muscle ischaemia unresponsive to high dose CRRT with EMiC-2 filter. Due to therapy failure, he was subsequently treated with the addition of a haemoadsorber (CytoSorb®) to the circuit. This reduced myoglobin and creatine kinase levels successfully despite ongoing tissue ischaemia. However, CytoSorb® was not enough to maintain microcirculatory perfusion, resulting in the eventual demise of the patient due to severity of the injury. Our report indicates that myoglobin was efficiently removed with CytoSorb® following exchange with the conventional high cut-off filter in continuous venovenous haemodialysis in severe traumatic rhabdomyolysis.
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http://dx.doi.org/10.1159/000505899DOI Listing
June 2021

Endothelial Responses in Sepsis.

Am J Respir Crit Care Med 2020 08;202(3):361-370

Medical Intensive Care Unit, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France.

Endothelial cells (ECs) are vascular, nonconventional immune cells that play a major role in the systemic response after bacterial infection to limit its dissemination. Triggered by exposure to pathogens, microbial toxins, or endogenous danger signals, EC responses are polymorphous, heterogeneous, and multifaceted. During sepsis, ECs shift toward a proapoptotic, proinflammatory, proadhesive, and procoagulant phenotype. In addition, glycocalyx damage and vascular tone dysfunction impair microcirculatory blood flow, leading to organ injury and, potentially, life-threatening organ failure. This review aims to cover the current understanding of the EC adaptive or maladaptive response to acute inflammation or bacterial infection based on compelling recent basic research and therapeutic clinical trials targeting microvascular and endothelial alterations during septic shock.
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http://dx.doi.org/10.1164/rccm.201910-1911TRDOI Listing
August 2020

Poor perfusion of the microvasculature in peritoneal metastases of ovarian cancer.

Clin Exp Metastasis 2020 04 1;37(2):293-304. Epub 2020 Feb 1.

Center for Gynecologic Oncology Amsterdam, Department of Gynecologic Oncology, The Netherlands Cancer Institute/Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Most women with epithelial ovarian cancer (EOC) suffer from peritoneal carcinomatosis upon first clinical presentation. Extensive peritoneal carcinomatosis has a poor prognosis and its pathophysiology is not well understood. Although treatment with systemic intravenous chemotherapy is often initially successful, peritoneal recurrences occur regularly. We hypothesized that insufficient or poorly-perfused microvasculature may impair the therapeutic efficacy of systemic intravenous chemotherapy but may also limit expansive and invasive growth characteristic of peritoneal EOC metastases. In 23 patients with advanced EOC or suspicion thereof, we determined the angioarchitecture and perfusion of the microvasculature in peritoneum and in peritoneal metastases using incident dark field (IDF) imaging. Additionally, we performed immunohistochemical analysis and 3-dimensional (3D) whole tumor imaging using light sheet fluorescence microscopy of IDF-imaged tissue sites. In all metastases, microvasculature was present but the angioarchitecture was chaotic and the vessel density and perfusion of vessels was significantly lower than in unaffected peritoneum. Immunohistochemical analysis showed expression of vascular endothelial growth factor and hypoxia inducible factor 1α, and 3D imaging demonstrated vascular continuity between metastases and the vascular network of the peritoneum beneath the elastic lamina of the peritoneum. We conclude that perfusion of the microvasculature within metastases is limited, which may cause hypoxia, affect the behavior of EOC metastases on the peritoneum and limit the response of EOC metastases to systemic treatment.
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http://dx.doi.org/10.1007/s10585-020-10024-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138772PMC
April 2020

Activation of the Nitric Oxide Pathway and Acute Myocardial Infarction Complicated by Acute Kidney Injury.

Cardiorenal Med 2020 20;10(2):85-96. Epub 2020 Jan 20.

Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.

Background/aims: The pathophysiology of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients remains poorly explored. The involvement of the nitric oxide (NO) pathway has been demonstrated in experimental ischemic AKI. The aim of this study was to assess the predictive value of circulating biomarkers of the NO pathway for AKI in STEMI patients.

Methods: Four hundred and twenty-seven STEMI patients treated with primary percutaneous coronary intervention were included. The primary end point was AKI. Biomarkers of the NO pathway (plasma superoxide dismutase [SOD], uric acid, nitrite/nitrate [NOx], neopterin) as well as cardiac biomarkers (B-type natriuretic peptide [BNP] and troponin) were sampled 12 h after admission. The predictive value of circulating biomarkers was evaluated in addition to the multivariate clinical model.

Results: AKI developed in 8.9% of patients. The 3-month mortality was significantly higher in patients with AKI (34.2 vs. 4.1%; p < 0.001). SOD, uric acid, NOx, neopterin, BNP and troponin were significantly associated with the development of AKI (area under curve [AUC]-receiver operating curve [ROC] ranging between 0.70 and 0.81). In multivariate analysis cardiogenic shock, neopterin, NOx and troponin were independent predictors of AKI. AUC-ROC of the association of multibiomarkers and clinical model was 0.90 and outperformed the predictive value of the clinical model alone. OR of NOx ≥45 µmol/L was 8.0 (95% CI 3.1-20.6) for AKI.

Conclusion: Biomarkers of the NO pathway are associated with the development of AKI in STEMI patients. These results provide insights into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway.
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http://dx.doi.org/10.1159/000503718DOI Listing
January 2020

Intestinal Mucosal and Serosal Microcirculation at the Planned Anastomosis during Abdominal Surgery.

Eur Surg Res 2019 14;60(5-6):248-256. Epub 2020 Jan 14.

Department of Anesthesiology, Intensive Care and Pain Medicine, St. Antonius Hospital, Nieuwegein, The Netherlands.

Introduction: Intestinal blood flow is often named as a key factor in the pathophysiology of anastomotic leakage. The distribution between mucosal and serosal microperfusion during surgery remains to be elucidated.

Objective: The aim of this study was to assess if the mucosal microcirculation of the intestine is more vulnerable to a surgical hit than the serosal microcirculation during surgery.

Methods: In an observational cohort study (n = 9 patients), the microcirculation of the bowel serosa and mucosa was visualized with incident dark-field imaging during surgery. At the planned anastomosis, the following microcirculatory parameters were determined: microvascular flow index (MFI), percentage of perfused vessels (PPV), perfused vessel density (PVD), and total vessel density (TVD). Data are presented as median (interquartile range [IQR]).

Results: Perfusion parameters and vessel density were significantly higher for the mucosa than the serosal microcirculation at the planned site for anastomosis or stoma. Mucosal MFI was 3.00 (IQR 3.00-3.00) compared to a serosal MFI of 2.75 (IQR 2.21-2.94), p = 0.03. The PPV was 99% (IQR 98-100) versus 92% (IQR 66-94), p = 0.01. The TVD was 16.77 mm/mm2 (IQR 13.04-18.01) versus 10.42 mm/mm2 (IQR 9.36-11.81), p = 0.01, and the PVD was 15.44 mm/mm2 (IQR 13.04-17.78) versus 9.02 mm/mm2 (IQR 6.43-9.43), p = 0.01.

Conclusions: The mucosal microcirculation was preserved, while lower perfusion of the serosa was found at the planned anastomosis or stoma during surgery. Further research is needed to link our observations to the clinically relevant endpoint of anastomotic leakage.
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http://dx.doi.org/10.1159/000505325DOI Listing
June 2020

Microcirculation: Physiology, Pathophysiology, and Clinical Application.

Blood Purif 2020 18;49(1-2):143-150. Epub 2019 Dec 18.

Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands,

This paper briefly reviews the physiological components of the microcirculation, focusing on its function in homeostasis and its central function in the realization of oxygen transport to tissue cells. Its pivotal role in the understanding of circulatory compromise in states of shock and renal compromise is discussed. Our introduction of hand-held vital microscopes (HVM) to clinical medicine has revealed the importance of the microcirculation as a central target organ in states of critical illness and inadequate response to therapy. Technical and methodological developments have been made in hardware and in software including our recent introduction and validation of automatic analysis software called MicroTools, which now allows point-of-care use of HVM imaging at the bedside for instant availability of functional microcirculatory parameters needed for microcirculatory targeted resuscitation procedures to be a reality.
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http://dx.doi.org/10.1159/000503775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114900PMC
December 2020

Investigating the physiology of normothermic ex vivo heart perfusion in an isolated slaughterhouse porcine model used for device testing and training.

BMC Cardiovasc Disord 2019 11 11;19(1):254. Epub 2019 Nov 11.

Department Cardiothoracic Surgery, Amsterdam University Medical Center, Meibergdreef 9, Amsterdam, The Netherlands.

Background: The PhysioHeart™ is a mature acute platform, based isolated slaughterhouse hearts and able to validate cardiac devices and techniques in working mode. Despite perfusion, myocardial edema and time-dependent function degradation are reported. Therefore, monitoring several variables is necessary to identify which of these should be controlled to preserve the heart function. This study presents biochemical, electrophysiological and hemodynamic changes in the PhysioHeart™ to understand the pitfalls of ex vivo slaughterhouse heart hemoperfusion.

Methods: Seven porcine hearts were harvested, arrested and revived using the PhysioHeart™. Cardiac output, SaO2, glucose and pH were maintained at physiological levels. Blood analyses were performed hourly and unipolar epicardial electrograms (UEG), pressures and flows were recorded to assess the physiological performance.

Results: Normal cardiac performance was attained in terms of mean cardiac output (5.1 ± 1.7 l/min) and pressures but deteriorated over time. Across the experiments, homeostasis was maintained for 171.4 ± 54 min, osmolarity and blood electrolytes increased significantly between 10 and 80%, heart weight increased by 144 ± 41 g, free fatty acids (- 60%), glucose and lactate diminished, ammonia increased by 273 ± 76% and myocardial necrosis and UEG alterations appeared and aggravated. Progressively deteriorating electrophysiological and hemodynamic functions can be explained by reperfusion injury, waste product intoxication (i.e. hyperammonemia), lack of essential nutrients, ion imbalances and cardiac necrosis as a consequence of hepatological and nephrological plasma clearance absence.

Conclusions: The PhysioHeart™ is an acute model, suitable for cardiac device and therapy assessment, which can precede conventional animal studies. However, observations indicate that ex vivo slaughterhouse hearts resemble cardiac physiology of deteriorating hearts in a multi-organ failure situation and signalize the need for plasma clearance during perfusion to attenuate time-dependent function degradation. The presented study therefore provides an in-dept understanding of the sources and reasons causing the cardiac function loss, as a first step for future effort to prolong cardiac perfusion in the PhysioHeart™. These findings could be also of potential interest for other cardiac platforms.
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http://dx.doi.org/10.1186/s12872-019-1242-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849278PMC
November 2019