Background: Assessment of the microcirculation is a promising target for the hemodynamic manageme... more Background: Assessment of the microcirculation is a promising target for the hemodynamic management of critically ill patients. However, just as the sole reliance on macrocirculatory parameters, single static parameters of the microcirculation may not represent a sufficient guide. Our hypothesis was that by serial topical application of acetylcholine (ACH) and nitroglycerin (NG), the sublingual microcirculation can be challenged to determine its endothelial cell-dependent and smooth muscledependent physiological reserve capacity. Methods: In 41 healthy subjects, sublingual capillary microscopy was performed before and after topical application of ACH and NG. Total vessel density (TVD) was assessed in parallel using manual computer-assisted image analysis as well as a fully automated analysis pathway utilizing a newly developed computer algorithm. Flow velocity was assessed using space-time diagrams of the venules as well as the algorithm-based calculation of an average perfused speed indicator (APSI). Results: No change in all measured parameters was detected after sublingual topical application of ACH. Sublingual topical application of NG however led to an increase in TVD, space-time diagram-derived venular flow velocity and APSI. No difference was detected in heart rate, blood pressure, and cardiac output as measured by echocardiography, as well as in plasma nitric oxide metabolite content before and after the topical application of ACH and NG. Conclusions: In healthy subjects, the sublingual microcirculatory physiological reserve can be assessed non-invasively by topical application of nitroglycerin without affecting systemic circulation.
Background: The PhysioHeart™ is a mature acute platform, based isolated slaughterhouse hearts and... more 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 timedependent 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.
Ischemia/reperfusion injury and inflammation are associated with microcirculatory dysfunction, en... more Ischemia/reperfusion injury and inflammation are associated with microcirculatory dysfunction, endothelial injury and glycocalyx degradation. This study aimed to assess microcirculation in the sublingual, intestinal and the (remnant) liver in patients undergoing major liver resection, to define microcirculatory leukocyte activation and its association with glycocalyx degradation. In this prospective observational study, the microcirculation was assessed at the beginning of surgery (T0), end of surgery (T1) and 24 h after surgery (T2) using Incident Dark Field imaging. Changes in vessel density, blood flow and leukocyte behaviour were monitored, as well as clinical parameters. Syndecan-1 levels as a parameter of glycocalyx degradation were analysed. 19 patients were included. Sublingual microcirculation showed a significant increase in the number of rolling leukocytes between T0 and T1 (1.5 [0.7-1.8] vs. 3.7 [1.7-5.4] Ls/C-PCV/4 s respectively, p = 0.001), and remained high at T2 when compared to T0 (3.8 [3-8.5] Ls/C-PCV/4 s, p = 0.006). The microvascular flow decreased at T2 (2.4 ± 0.3 vs. baseline 2.8 ± 0.2, respectively, p < 0.01). Duration of vascular inflow occlusion was associated with significantly higher numbers of sublingual microcirculatory rolling leukocytes. Syndecan-1 increased from T0 to T1 (42 [25-56] vs. 107 [86-164] ng/mL, p < 0.001). The microcirculatory perfusion was characterized by low convection capacity and high number of rolling leukocytes. The ability to sublingually monitor the rolling behaviour of the microcirculatory leukocytes allows for early identification of patients at risk of increased inflammatory response following major liver resection. Liver resection (LR) remains the only curative option for liver malignancies 1. Systemic inflammatory response as a result of ischemia reperfusion injury (IRI) during vascular inflow occlusion (VIO), surgical trauma and preoperative co-morbidities may contribute to poor postoperative outcomes following LR 2-7. Liver IRI induces local expression of proinflammatory cytokines, promoting the recruitment and activation of Kupffer cells (KC). Activated KC are signalled for transmigration into the liver parenchyma where they release reactive oxygen species contributing to oxidative stress in the liver as well as in distant organs 8. During the late phase of inflammation, cytokine production spills into the systemic circulation resulting in global activation of neutrophils and lymphocytes. Studies have shown that apart from the liver, multiple organs are affected by this process such as; myocardium, pancreas, intestines, kidneys, adrenal glands and the lungs 8. Leukocyte activation in multiple organs occurs at the endothelial barrier of the microvasculature where oxidative stress, decreased nitrous oxide production and a surge in pro-inflammatory cytokine production result in accumulation of activated leukocytes and degradation of endothelium 9. Studies have shown that degradation of the endothelium results in capillary leakage and disruption of capillaries 10,11. The glycocalyx is the anti-adhesive layer of the endothelium, whilst the disruption of the glycocalyx stimulates firm adhesion of the leukocytes 12. The assessment of leukocyte-endothelial interactions within the microcirculation becomes a potential target for therapeutic interventions 13,14. Microcirculatory bedside monitoring has been made possible through the introduction of handheld vital microscopes (HVM). These devices are to date, predominately applied sublingually
The Renal Microcirculation in Sepsis CHAPTER 2 19 THE RENAL MICROCIRCULATION IN SEPSIS and, thus,... more The Renal Microcirculation in Sepsis CHAPTER 2 19 THE RENAL MICROCIRCULATION IN SEPSIS and, thus, cause vasodilatation (30,31). Studies had shown evidence that RBC`s become less deformable and aggregate during sepsis (32,33) promoting microcirculatory dysfunction. These described sequel of events lead to massive microcirculatory collapse, which specifically influences the renal function, whereby the physiological vascular mechanism responsible for the vasotone regulation necessary for meeting oxygen needs is no longer functional and microcirculatory patency becomes impaired. Renal Microvascular Structures The functional morphology of the microcirculatory networks in the different organs systems is highly heterogeneous, having adapted itself the metabolic demand and function of each organ type (34) as illustrated in Fig 1. In the kidney, the renal artery branches continue to the inter-lobar artery, arcuate artery and interlobular artery, which supply blood to the afferent artery. A unique arteriolar capillary network in the present glomerulus is fed by the afferent arteriole in both the cortex and medulla. The nephron, consisting of the glomerulus, Bowman capsules and tubules, maintains the excretion, reabsorption and secretion functions of the kidney. In addition to the glomerular arteriolar structure, the renal cortex has a peri-tubular capillary network arising from efferent arterioles surrounding the proximal and distal convoluted tubules to maintain large reabsorption of glomerular filtrate. In contrast, the vasa recta is located specifically in the medulla and is fed by efferent arterioles and peri-glomerular shunt pathways located at juxta-medullary glomeruli follows to the loops of Henle´ and collecting ducts deep into the medulla. The parallel arrangement of descending vasa recta (DVR) and ascending vasa recta (AVR) with descending (DL) and ascending limbs (AL) gives rise to a counter-current exchange system that maintains the cortico-medullary osmotic gradient established from counter-current multiplication by the loops of Henle crucial for concentrating the urine (35-37) while maintaining adequate oxygen and nutrient delivery as well as metabolic clearance (38). Moreover, this parallel arrangement has a key role in regulating regional perfusion between the outer versus inner medulla (35). Contraction of the DVR results in the redirection of blood to the outer medullary interbundle capillaries (36) (Figure 1). A consequence of this structural arrangement is that there is a low oxygen tension in the medulla with medullary partial pressure of oxygen between 30 and 40 mmHg compared of the 40-60 mmHg in the cortex (39). Renal blood flow is also regionally specific, and tightly regulated by tubuloglomerular feedback mechanism in the cortex. Although only a small fraction (~10%) of the total renal blood flow enters the renal medulla, the regulation of medullar flow is important because renal blood flow seems to play a key role in the regulation of tubular function, sodium excretion, fluid volume control, and ultimately blood pressure regulation (40) which is locally
International Journal of Artificial Organs, Oct 17, 2019
Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tool... more Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, −14.9 ± 6.3%/h vs −9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, −11.8 ± 3.4%/h vs −5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform.
(CCI), it seems they do not influence the outcome in ALPPS. Despite the Age-adjusted-CCI (aCCI) i... more (CCI), it seems they do not influence the outcome in ALPPS. Despite the Age-adjusted-CCI (aCCI) is the most used tool to weight comorbidities in ALPPS Literature, it does not correlate to postoperative outcome, too. A possible explanation may be a wrong estimation of the weight of the neoplastic diagnosis in this type of surgery, considering that secondary tumors, as colorectal liver metastases, are weighted with 4 points more than primary tumor of the liver, as hepatocellular-and cholangiocarcinoma.We here propose a Corrected Age-adjusted Charlson Comorbidity Index (CaCCI) to predict postoperative 90-days mortality in patients undergoing ALPPS. Methods: Thirteen centers participated to this retrospective multicentric study. A risk analysis based on patients' characteristics and underlying disease was performed to recalibrate CCI on the basis of the relative size of logistic model regression coefficients. A nonparametric receiver operating characteristic (ROC) analysis was performed to estimate the predictive ability of CCI, aCCI and CaCCI. A good predictivity ability was defined as a C-statistic equal or greater than 0,7. Results: 449 patients were included. Mortality was observed in 65 cases (14,2%). CaCCI was generated on CCI corrected for age, weight of comorbidities and tumor type, with primary tumors weighted more that secundary. The predictive ability of the different scores measured was 0,445 for CCI, 0,523 for aCCI and 0,751 for CaCCI. Conclusions: The proposed CaCCI, unlike CCI and aCCI, has a good prediction capacity of postoperative mortality and can be easily integrated in the preoperative workout to improve patient selection.
Acute kidney injury (AKI) is frequently seen in patients with hemorrhagic shock due to hypotensio... more Acute kidney injury (AKI) is frequently seen in patients with hemorrhagic shock due to hypotension, tissue hypoxia, and inflammation despite adequate resuscitation. There is a lack of information concerning the alteration of renal microcirculation and perfusion during shock and resuscitation. The aim of this study was to investigate the possible role of renal microcirculatory alterations on development of renal dysfunction in a pig model of non-traumatic hemorrhagic shock (HS) induced AKI.Fully instrumented female pigs were divided into the two groups as Control (n = 6) and HS (n = 11). HS was achieved by withdrawing blood until mean arterial pressure (MAP) reached around 50 mmHg. After an hour cessation period, fluid resuscitation with balanced crystalloid was started for the duration of 1 h. The systemic and renal hemodynamics, renal microcirculatory perfusion (contrast-enhanced ultrasound (CEUS)) and the sublingual microcirculation were measured.CEUS peak enhancement was signific...
Surgical preparation and blood gas measurements are detailed in the supplemental data. Figure S1.... more Surgical preparation and blood gas measurements are detailed in the supplemental data. Figure S1. Myeloperoxydase (MPO) immunostaining and neutrophil gelatinase-associated lipocalin (NGAL) immunostaining in kidney sections in the four groups. **P
ABSTRACT Acute normovolemic hemodilution (ANH) is associated with low oxygen carrying capacity of... more ABSTRACT Acute normovolemic hemodilution (ANH) is associated with low oxygen carrying capacity of blood and purposed to cause renal injury in perioperative setting. It is best accomplished in a perioperative setting by a colloid such as hydroxyl ethyl starch (HES) due its capacity to fill the vascular compartment and maintain colloidal pressure. However, alterations of intra renal microvascular perfusion, flow and its effects on renal function and damage during ANH has not been sufficiently clarified. Based on the extensive use of HES in the perioperative setting we tested the hypothesis that the use of HES during ANH is able to perfuse the kidney microcirculation adequately without causing renal dysfunction and injury in pigs. Hemodilution (n = 8) was performed by stepwise replacing blood with HES to hematocrit (Hct) levels of 20% (T1), 15% (T2), and 10% (T3). Seven control animals were investigated. Systemic and renal hemodynamics were monitored. Renal microcirculatory perfusion was visualized and quantified using contrast-enhanced ultrasound (CEUS) and laser speckle imaging (LSI). In addition, sublingual microcirculation was measured by handheld vital microscopy (HVM). Intrarenal mean transit time of ultrasound contrast agent (IRMTT-CEUS) was reduced in the renal cortex at Hct 10% in comparison to control at T3 (1.4 ± 0.6 vs. 2.2 ± 0.7 seconds, respectively, P < 0.05). Although renal function was preserved, the serum neutrophil gelatinase-associated lipocalin (NGAL) levels was higher at Hct 10% (0.033 ± 0.004 pg/μg protein) in comparison to control at T3 (0.021 ± 0.002 pg/μg protein. A mild correlation between CO and IRMTT (renal RBC velocity) (r −0.53; P = 0.001) and CO and NGAL levels (r 0.66; P = 0.001) was also found. Our results show that HES induced ANH is associated with a preserved intra renal blood volume, perfusion, and function in the clinical range of Hct (<15%). However, at severely low Hct (10%) ANH was associated with renal injury as indicated by increased NGAL levels. Changes in renal microcirculatory flow (CEUS and LSI) followed those seen in the sublingual microcirculation measured with HVM.
Acute kidney injury (AKI) is a serious multifactorial conditions accompanied by the loss of funct... more Acute kidney injury (AKI) is a serious multifactorial conditions accompanied by the loss of function and damage. The renal microcirculation plays a crucial role in maintaining the kidney’s functional and structural integrity for oxygen and nutrient supply and waste product removal. However, alterations in microcirculation and oxygenation due to renal perfusion defects, hypoxia, renal tubular, and endothelial damage can result in AKI and the loss of renal function regardless of systemic hemodynamic changes. The unique structural organization of the renal microvasculature and the presence of autoregulation make it difficult to understand the mechanisms and the occurrence of AKI following disorders such as septic, hemorrhagic, or cardiogenic shock; ischemia/reperfusion; chronic heart failure; cardiorenal syndrome; and hemodilution. In this review, we describe the organization of microcirculation, autoregulation, and pathophysiological alterations leading to AKI. We then suggest innovat...
Background: The microvascular effects occurring after unilateral preoperative portal vein emboliz... more Background: The microvascular effects occurring after unilateral preoperative portal vein embolization (PVE) are poorly understood. The aim of this study was to assess the microvascular changes in the embolized and the non-embolized lobes after right PVE. Methods: Videos of the hepatic microcirculation in patients undergoing right hemihepatectomy following PVE were recorded using a handheld vital microscope (Cytocam) based on incident dark field imaging. Hepatic microcirculation was measured in the embolized and the non-embolized lobes at laparotomy, 3-6 weeks after PVE. The following microcirculatory parameters were assessed: total vessel density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel (PPV), perfused vessel density (PVD), sinusoidal diameter (SinD) and the absolute red blood cell velocity (RBCv). Results: 16 patients after major liver resection were included, 8 with and 8 without preoperative PVE. Microvascular density parameters were higher in the non-embolized lobes when compared to the embolized lobes (TVD: 40.3 ± 8.9 vs. 26.8 ± 4.6 mm/mm 2 (p < 0.003), PVD: 40.3 ± 8.8 vs. 26.7 ± 4.7 mm/mm 2 (p < 0.002), SinD: 9.2 ± 1.7 vs. 6.3 ± 0.8 mm (p < 0.040)). RBCv, PPV and the MFI were not significantly different. Conclusion: The non-embolized lobe has a significantly higher microvascular density, however without differences in microvascular flow. These findings indicate increased angiogenesis in the hypertrophic lobe.
Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase... more Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n=18) were subjected to renal ischemia (30min) and reperfusion (I/R), or sham-operated. In a second model, rats (n=18) received a 30min infusion of lipopolysaccharide (LPS; 2.5mg/kg), or saline, and fluid resuscitation. In both models, recAP (1000U/kg) was administered intravenously (15min before reperfusion, or 90min after LPS). Following recAP treatment, I/R-induced changes in renal blood flow, renal vascular resistance and oxygen delivery at early, and cortical microvascular oxygen tension ...
to identify factors associated with hospital mortality in the subgroup of ARDS patients with no r... more to identify factors associated with hospital mortality in the subgroup of ARDS patients with no risk factors. Methods: Ancillary study of an international, multicenter, prospective cohort study (LUNG SAFE study[1]). Patients meeting ARDS criteria (Berlin definition) on day 1 or 2 of acute hypoxemic respiratory failure onset were included in the study and categorized as having "common" risk factors or not. Results: Among the 2813 patients presenting ARDS in the first 48 h, 266 patients (9.4 %) had no ARDS risk factor identified at admission. Table shows the final ARDS risk factor identified in patients with or without initial risk factor identified. The patients with no risk factor were older, had more frequent previously known chronic diseases and presented with less severe SOFA (8.7 ± 3.9 vs 9.5 ± 4.1, p < 0.001) and non-pulmonary (5.4 ± 3.9 vs 6.3 ± 4.1, p < 0.001) SOFA scores. ICU mortality was lower in ARDS patients with no risk factor than in others (28.6 % vs 34.9 %, p = 0.047), but in-hospital mortality was not (35.7 % vs 39.8 %, p = 0.20). The lack of ARDS risk factor was not associated with hospital mortality (adjusted OR = 0.86 [0.65-1.13], p = 0.29). In the subgroup of patients with no ARDS risk factor, age, SOFA, concomitant heart failure, and administration of steroids within 72 hours of ARDS onset were associated with hospital mortality (Table ). Conclusions: Almost ten percent of patients with ARDS had no risk factor identified and exhibit a different clinical phenotype than others. Future research aimed at studying management strategies in this subgroup of patients is warranted.
Introduction: Critically ill children in the pediatric intensive care unit (PICU) are at high ris... more Introduction: Critically ill children in the pediatric intensive care unit (PICU) are at high risk for developing nutritional deficiencies and undernutrition is known to be a risk factor for morbidity and mortality. Malnutrition represents a continuous spectrum ranging from marginal nutrient status to severe metabolic and functional alterations and this in turn, affects clinical outcome. Objectives: The aim of the study was to assess nutritional status of critically ill children admitted to the PICU and its association to clinical outcomes. Methods: Critically ill children age 6 months to 18 years were prospectively enrolled on PICU admission. Nutritional status was assessed by weight for age (WFA: underweight), weight for height (WFH: wasting), height for age (HFA: stunting) z-scores and mid upper arm circumference (MUAC: wasting) according to the WHO. (1,2) Malnutrition was defined as mild, moderate, and severe if z-scores were > −1, > − 2, and > −3, respectively. Hospital and PICU length of stay (LOS), duration of mechanical ventilation (MV), and risk of mortality (ROM) by the Pediatric Index of Mortality 2 (PIM2) were obtained. Sensitivity and specificity of the MUAC to identify children with wasting (WFH) were calculated. Results: Two hundred and fifty children (136 males), aged 81 months (23-167; median (25-75 th IQR)), were prospectively included in the study. The hospital LOS was 8 (4-16) days; PICU LOS: 2 (1-4) days; duration of MV, 0 (0-1.5) days;
Background: Perioperative Acute Kidney Injury (AKI) caused by Ischemia-Reperfusion (IR) is a sign... more Background: Perioperative Acute Kidney Injury (AKI) caused by Ischemia-Reperfusion (IR) is a significant contributor to mortality and morbidity after major surgery. Furosemide is commonly used in postoperative patients to promote diuresis and reduce tissue edema. However, its effects on renal microcirculation, oxygenation and function after AKI are poorly understood. Herein, we investigated the effects of furosemide in rats subjected to IR insult. Methods: 24 Wistar albino rats were divided into 4 groups, with 6 in each; Sham-operated Control (C), Control + Furosemide (C+F), ischemia/reperfusion (IR), and IR+F. After induction of anaesthesia (BL), supra-aortic occlusion was applied to IR and IR+F groups for 45 minutes followed by ongoing reperfusion for 15 minutes (T1) and 2 hours(T2). Furosemide infusion was initiated simultaneously in the intervention groups after ischemia. Renal blood flow (RBF), vascular resistance (RVR), oxygen delivery (DO2ren) and consumption (VO2ren), sodium...
Journal of Clinical and Translational Research, 2020
Background: The consequences of acute normovolemic hemodilution (ANH) following different types o... more 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 (P=0.003, P=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 (P=0.02) and NS groups only (P<0.0001, P=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.
Background: Assessment of the microcirculation is a promising target for the hemodynamic manageme... more Background: Assessment of the microcirculation is a promising target for the hemodynamic management of critically ill patients. However, just as the sole reliance on macrocirculatory parameters, single static parameters of the microcirculation may not represent a sufficient guide. Our hypothesis was that by serial topical application of acetylcholine (ACH) and nitroglycerin (NG), the sublingual microcirculation can be challenged to determine its endothelial cell-dependent and smooth muscledependent physiological reserve capacity. Methods: In 41 healthy subjects, sublingual capillary microscopy was performed before and after topical application of ACH and NG. Total vessel density (TVD) was assessed in parallel using manual computer-assisted image analysis as well as a fully automated analysis pathway utilizing a newly developed computer algorithm. Flow velocity was assessed using space-time diagrams of the venules as well as the algorithm-based calculation of an average perfused speed indicator (APSI). Results: No change in all measured parameters was detected after sublingual topical application of ACH. Sublingual topical application of NG however led to an increase in TVD, space-time diagram-derived venular flow velocity and APSI. No difference was detected in heart rate, blood pressure, and cardiac output as measured by echocardiography, as well as in plasma nitric oxide metabolite content before and after the topical application of ACH and NG. Conclusions: In healthy subjects, the sublingual microcirculatory physiological reserve can be assessed non-invasively by topical application of nitroglycerin without affecting systemic circulation.
Background: The PhysioHeart™ is a mature acute platform, based isolated slaughterhouse hearts and... more 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 timedependent 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.
Ischemia/reperfusion injury and inflammation are associated with microcirculatory dysfunction, en... more Ischemia/reperfusion injury and inflammation are associated with microcirculatory dysfunction, endothelial injury and glycocalyx degradation. This study aimed to assess microcirculation in the sublingual, intestinal and the (remnant) liver in patients undergoing major liver resection, to define microcirculatory leukocyte activation and its association with glycocalyx degradation. In this prospective observational study, the microcirculation was assessed at the beginning of surgery (T0), end of surgery (T1) and 24 h after surgery (T2) using Incident Dark Field imaging. Changes in vessel density, blood flow and leukocyte behaviour were monitored, as well as clinical parameters. Syndecan-1 levels as a parameter of glycocalyx degradation were analysed. 19 patients were included. Sublingual microcirculation showed a significant increase in the number of rolling leukocytes between T0 and T1 (1.5 [0.7-1.8] vs. 3.7 [1.7-5.4] Ls/C-PCV/4 s respectively, p = 0.001), and remained high at T2 when compared to T0 (3.8 [3-8.5] Ls/C-PCV/4 s, p = 0.006). The microvascular flow decreased at T2 (2.4 ± 0.3 vs. baseline 2.8 ± 0.2, respectively, p < 0.01). Duration of vascular inflow occlusion was associated with significantly higher numbers of sublingual microcirculatory rolling leukocytes. Syndecan-1 increased from T0 to T1 (42 [25-56] vs. 107 [86-164] ng/mL, p < 0.001). The microcirculatory perfusion was characterized by low convection capacity and high number of rolling leukocytes. The ability to sublingually monitor the rolling behaviour of the microcirculatory leukocytes allows for early identification of patients at risk of increased inflammatory response following major liver resection. Liver resection (LR) remains the only curative option for liver malignancies 1. Systemic inflammatory response as a result of ischemia reperfusion injury (IRI) during vascular inflow occlusion (VIO), surgical trauma and preoperative co-morbidities may contribute to poor postoperative outcomes following LR 2-7. Liver IRI induces local expression of proinflammatory cytokines, promoting the recruitment and activation of Kupffer cells (KC). Activated KC are signalled for transmigration into the liver parenchyma where they release reactive oxygen species contributing to oxidative stress in the liver as well as in distant organs 8. During the late phase of inflammation, cytokine production spills into the systemic circulation resulting in global activation of neutrophils and lymphocytes. Studies have shown that apart from the liver, multiple organs are affected by this process such as; myocardium, pancreas, intestines, kidneys, adrenal glands and the lungs 8. Leukocyte activation in multiple organs occurs at the endothelial barrier of the microvasculature where oxidative stress, decreased nitrous oxide production and a surge in pro-inflammatory cytokine production result in accumulation of activated leukocytes and degradation of endothelium 9. Studies have shown that degradation of the endothelium results in capillary leakage and disruption of capillaries 10,11. The glycocalyx is the anti-adhesive layer of the endothelium, whilst the disruption of the glycocalyx stimulates firm adhesion of the leukocytes 12. The assessment of leukocyte-endothelial interactions within the microcirculation becomes a potential target for therapeutic interventions 13,14. Microcirculatory bedside monitoring has been made possible through the introduction of handheld vital microscopes (HVM). These devices are to date, predominately applied sublingually
The Renal Microcirculation in Sepsis CHAPTER 2 19 THE RENAL MICROCIRCULATION IN SEPSIS and, thus,... more The Renal Microcirculation in Sepsis CHAPTER 2 19 THE RENAL MICROCIRCULATION IN SEPSIS and, thus, cause vasodilatation (30,31). Studies had shown evidence that RBC`s become less deformable and aggregate during sepsis (32,33) promoting microcirculatory dysfunction. These described sequel of events lead to massive microcirculatory collapse, which specifically influences the renal function, whereby the physiological vascular mechanism responsible for the vasotone regulation necessary for meeting oxygen needs is no longer functional and microcirculatory patency becomes impaired. Renal Microvascular Structures The functional morphology of the microcirculatory networks in the different organs systems is highly heterogeneous, having adapted itself the metabolic demand and function of each organ type (34) as illustrated in Fig 1. In the kidney, the renal artery branches continue to the inter-lobar artery, arcuate artery and interlobular artery, which supply blood to the afferent artery. A unique arteriolar capillary network in the present glomerulus is fed by the afferent arteriole in both the cortex and medulla. The nephron, consisting of the glomerulus, Bowman capsules and tubules, maintains the excretion, reabsorption and secretion functions of the kidney. In addition to the glomerular arteriolar structure, the renal cortex has a peri-tubular capillary network arising from efferent arterioles surrounding the proximal and distal convoluted tubules to maintain large reabsorption of glomerular filtrate. In contrast, the vasa recta is located specifically in the medulla and is fed by efferent arterioles and peri-glomerular shunt pathways located at juxta-medullary glomeruli follows to the loops of Henle´ and collecting ducts deep into the medulla. The parallel arrangement of descending vasa recta (DVR) and ascending vasa recta (AVR) with descending (DL) and ascending limbs (AL) gives rise to a counter-current exchange system that maintains the cortico-medullary osmotic gradient established from counter-current multiplication by the loops of Henle crucial for concentrating the urine (35-37) while maintaining adequate oxygen and nutrient delivery as well as metabolic clearance (38). Moreover, this parallel arrangement has a key role in regulating regional perfusion between the outer versus inner medulla (35). Contraction of the DVR results in the redirection of blood to the outer medullary interbundle capillaries (36) (Figure 1). A consequence of this structural arrangement is that there is a low oxygen tension in the medulla with medullary partial pressure of oxygen between 30 and 40 mmHg compared of the 40-60 mmHg in the cortex (39). Renal blood flow is also regionally specific, and tightly regulated by tubuloglomerular feedback mechanism in the cortex. Although only a small fraction (~10%) of the total renal blood flow enters the renal medulla, the regulation of medullar flow is important because renal blood flow seems to play a key role in the regulation of tubular function, sodium excretion, fluid volume control, and ultimately blood pressure regulation (40) which is locally
International Journal of Artificial Organs, Oct 17, 2019
Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tool... more Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, −14.9 ± 6.3%/h vs −9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, −11.8 ± 3.4%/h vs −5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform.
(CCI), it seems they do not influence the outcome in ALPPS. Despite the Age-adjusted-CCI (aCCI) i... more (CCI), it seems they do not influence the outcome in ALPPS. Despite the Age-adjusted-CCI (aCCI) is the most used tool to weight comorbidities in ALPPS Literature, it does not correlate to postoperative outcome, too. A possible explanation may be a wrong estimation of the weight of the neoplastic diagnosis in this type of surgery, considering that secondary tumors, as colorectal liver metastases, are weighted with 4 points more than primary tumor of the liver, as hepatocellular-and cholangiocarcinoma.We here propose a Corrected Age-adjusted Charlson Comorbidity Index (CaCCI) to predict postoperative 90-days mortality in patients undergoing ALPPS. Methods: Thirteen centers participated to this retrospective multicentric study. A risk analysis based on patients' characteristics and underlying disease was performed to recalibrate CCI on the basis of the relative size of logistic model regression coefficients. A nonparametric receiver operating characteristic (ROC) analysis was performed to estimate the predictive ability of CCI, aCCI and CaCCI. A good predictivity ability was defined as a C-statistic equal or greater than 0,7. Results: 449 patients were included. Mortality was observed in 65 cases (14,2%). CaCCI was generated on CCI corrected for age, weight of comorbidities and tumor type, with primary tumors weighted more that secundary. The predictive ability of the different scores measured was 0,445 for CCI, 0,523 for aCCI and 0,751 for CaCCI. Conclusions: The proposed CaCCI, unlike CCI and aCCI, has a good prediction capacity of postoperative mortality and can be easily integrated in the preoperative workout to improve patient selection.
Acute kidney injury (AKI) is frequently seen in patients with hemorrhagic shock due to hypotensio... more Acute kidney injury (AKI) is frequently seen in patients with hemorrhagic shock due to hypotension, tissue hypoxia, and inflammation despite adequate resuscitation. There is a lack of information concerning the alteration of renal microcirculation and perfusion during shock and resuscitation. The aim of this study was to investigate the possible role of renal microcirculatory alterations on development of renal dysfunction in a pig model of non-traumatic hemorrhagic shock (HS) induced AKI.Fully instrumented female pigs were divided into the two groups as Control (n = 6) and HS (n = 11). HS was achieved by withdrawing blood until mean arterial pressure (MAP) reached around 50 mmHg. After an hour cessation period, fluid resuscitation with balanced crystalloid was started for the duration of 1 h. The systemic and renal hemodynamics, renal microcirculatory perfusion (contrast-enhanced ultrasound (CEUS)) and the sublingual microcirculation were measured.CEUS peak enhancement was signific...
Surgical preparation and blood gas measurements are detailed in the supplemental data. Figure S1.... more Surgical preparation and blood gas measurements are detailed in the supplemental data. Figure S1. Myeloperoxydase (MPO) immunostaining and neutrophil gelatinase-associated lipocalin (NGAL) immunostaining in kidney sections in the four groups. **P
ABSTRACT Acute normovolemic hemodilution (ANH) is associated with low oxygen carrying capacity of... more ABSTRACT Acute normovolemic hemodilution (ANH) is associated with low oxygen carrying capacity of blood and purposed to cause renal injury in perioperative setting. It is best accomplished in a perioperative setting by a colloid such as hydroxyl ethyl starch (HES) due its capacity to fill the vascular compartment and maintain colloidal pressure. However, alterations of intra renal microvascular perfusion, flow and its effects on renal function and damage during ANH has not been sufficiently clarified. Based on the extensive use of HES in the perioperative setting we tested the hypothesis that the use of HES during ANH is able to perfuse the kidney microcirculation adequately without causing renal dysfunction and injury in pigs. Hemodilution (n = 8) was performed by stepwise replacing blood with HES to hematocrit (Hct) levels of 20% (T1), 15% (T2), and 10% (T3). Seven control animals were investigated. Systemic and renal hemodynamics were monitored. Renal microcirculatory perfusion was visualized and quantified using contrast-enhanced ultrasound (CEUS) and laser speckle imaging (LSI). In addition, sublingual microcirculation was measured by handheld vital microscopy (HVM). Intrarenal mean transit time of ultrasound contrast agent (IRMTT-CEUS) was reduced in the renal cortex at Hct 10% in comparison to control at T3 (1.4 ± 0.6 vs. 2.2 ± 0.7 seconds, respectively, P < 0.05). Although renal function was preserved, the serum neutrophil gelatinase-associated lipocalin (NGAL) levels was higher at Hct 10% (0.033 ± 0.004 pg/μg protein) in comparison to control at T3 (0.021 ± 0.002 pg/μg protein. A mild correlation between CO and IRMTT (renal RBC velocity) (r −0.53; P = 0.001) and CO and NGAL levels (r 0.66; P = 0.001) was also found. Our results show that HES induced ANH is associated with a preserved intra renal blood volume, perfusion, and function in the clinical range of Hct (<15%). However, at severely low Hct (10%) ANH was associated with renal injury as indicated by increased NGAL levels. Changes in renal microcirculatory flow (CEUS and LSI) followed those seen in the sublingual microcirculation measured with HVM.
Acute kidney injury (AKI) is a serious multifactorial conditions accompanied by the loss of funct... more Acute kidney injury (AKI) is a serious multifactorial conditions accompanied by the loss of function and damage. The renal microcirculation plays a crucial role in maintaining the kidney’s functional and structural integrity for oxygen and nutrient supply and waste product removal. However, alterations in microcirculation and oxygenation due to renal perfusion defects, hypoxia, renal tubular, and endothelial damage can result in AKI and the loss of renal function regardless of systemic hemodynamic changes. The unique structural organization of the renal microvasculature and the presence of autoregulation make it difficult to understand the mechanisms and the occurrence of AKI following disorders such as septic, hemorrhagic, or cardiogenic shock; ischemia/reperfusion; chronic heart failure; cardiorenal syndrome; and hemodilution. In this review, we describe the organization of microcirculation, autoregulation, and pathophysiological alterations leading to AKI. We then suggest innovat...
Background: The microvascular effects occurring after unilateral preoperative portal vein emboliz... more Background: The microvascular effects occurring after unilateral preoperative portal vein embolization (PVE) are poorly understood. The aim of this study was to assess the microvascular changes in the embolized and the non-embolized lobes after right PVE. Methods: Videos of the hepatic microcirculation in patients undergoing right hemihepatectomy following PVE were recorded using a handheld vital microscope (Cytocam) based on incident dark field imaging. Hepatic microcirculation was measured in the embolized and the non-embolized lobes at laparotomy, 3-6 weeks after PVE. The following microcirculatory parameters were assessed: total vessel density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel (PPV), perfused vessel density (PVD), sinusoidal diameter (SinD) and the absolute red blood cell velocity (RBCv). Results: 16 patients after major liver resection were included, 8 with and 8 without preoperative PVE. Microvascular density parameters were higher in the non-embolized lobes when compared to the embolized lobes (TVD: 40.3 ± 8.9 vs. 26.8 ± 4.6 mm/mm 2 (p < 0.003), PVD: 40.3 ± 8.8 vs. 26.7 ± 4.7 mm/mm 2 (p < 0.002), SinD: 9.2 ± 1.7 vs. 6.3 ± 0.8 mm (p < 0.040)). RBCv, PPV and the MFI were not significantly different. Conclusion: The non-embolized lobe has a significantly higher microvascular density, however without differences in microvascular flow. These findings indicate increased angiogenesis in the hypertrophic lobe.
Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase... more Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n=18) were subjected to renal ischemia (30min) and reperfusion (I/R), or sham-operated. In a second model, rats (n=18) received a 30min infusion of lipopolysaccharide (LPS; 2.5mg/kg), or saline, and fluid resuscitation. In both models, recAP (1000U/kg) was administered intravenously (15min before reperfusion, or 90min after LPS). Following recAP treatment, I/R-induced changes in renal blood flow, renal vascular resistance and oxygen delivery at early, and cortical microvascular oxygen tension ...
to identify factors associated with hospital mortality in the subgroup of ARDS patients with no r... more to identify factors associated with hospital mortality in the subgroup of ARDS patients with no risk factors. Methods: Ancillary study of an international, multicenter, prospective cohort study (LUNG SAFE study[1]). Patients meeting ARDS criteria (Berlin definition) on day 1 or 2 of acute hypoxemic respiratory failure onset were included in the study and categorized as having "common" risk factors or not. Results: Among the 2813 patients presenting ARDS in the first 48 h, 266 patients (9.4 %) had no ARDS risk factor identified at admission. Table shows the final ARDS risk factor identified in patients with or without initial risk factor identified. The patients with no risk factor were older, had more frequent previously known chronic diseases and presented with less severe SOFA (8.7 ± 3.9 vs 9.5 ± 4.1, p < 0.001) and non-pulmonary (5.4 ± 3.9 vs 6.3 ± 4.1, p < 0.001) SOFA scores. ICU mortality was lower in ARDS patients with no risk factor than in others (28.6 % vs 34.9 %, p = 0.047), but in-hospital mortality was not (35.7 % vs 39.8 %, p = 0.20). The lack of ARDS risk factor was not associated with hospital mortality (adjusted OR = 0.86 [0.65-1.13], p = 0.29). In the subgroup of patients with no ARDS risk factor, age, SOFA, concomitant heart failure, and administration of steroids within 72 hours of ARDS onset were associated with hospital mortality (Table ). Conclusions: Almost ten percent of patients with ARDS had no risk factor identified and exhibit a different clinical phenotype than others. Future research aimed at studying management strategies in this subgroup of patients is warranted.
Introduction: Critically ill children in the pediatric intensive care unit (PICU) are at high ris... more Introduction: Critically ill children in the pediatric intensive care unit (PICU) are at high risk for developing nutritional deficiencies and undernutrition is known to be a risk factor for morbidity and mortality. Malnutrition represents a continuous spectrum ranging from marginal nutrient status to severe metabolic and functional alterations and this in turn, affects clinical outcome. Objectives: The aim of the study was to assess nutritional status of critically ill children admitted to the PICU and its association to clinical outcomes. Methods: Critically ill children age 6 months to 18 years were prospectively enrolled on PICU admission. Nutritional status was assessed by weight for age (WFA: underweight), weight for height (WFH: wasting), height for age (HFA: stunting) z-scores and mid upper arm circumference (MUAC: wasting) according to the WHO. (1,2) Malnutrition was defined as mild, moderate, and severe if z-scores were > −1, > − 2, and > −3, respectively. Hospital and PICU length of stay (LOS), duration of mechanical ventilation (MV), and risk of mortality (ROM) by the Pediatric Index of Mortality 2 (PIM2) were obtained. Sensitivity and specificity of the MUAC to identify children with wasting (WFH) were calculated. Results: Two hundred and fifty children (136 males), aged 81 months (23-167; median (25-75 th IQR)), were prospectively included in the study. The hospital LOS was 8 (4-16) days; PICU LOS: 2 (1-4) days; duration of MV, 0 (0-1.5) days;
Background: Perioperative Acute Kidney Injury (AKI) caused by Ischemia-Reperfusion (IR) is a sign... more Background: Perioperative Acute Kidney Injury (AKI) caused by Ischemia-Reperfusion (IR) is a significant contributor to mortality and morbidity after major surgery. Furosemide is commonly used in postoperative patients to promote diuresis and reduce tissue edema. However, its effects on renal microcirculation, oxygenation and function after AKI are poorly understood. Herein, we investigated the effects of furosemide in rats subjected to IR insult. Methods: 24 Wistar albino rats were divided into 4 groups, with 6 in each; Sham-operated Control (C), Control + Furosemide (C+F), ischemia/reperfusion (IR), and IR+F. After induction of anaesthesia (BL), supra-aortic occlusion was applied to IR and IR+F groups for 45 minutes followed by ongoing reperfusion for 15 minutes (T1) and 2 hours(T2). Furosemide infusion was initiated simultaneously in the intervention groups after ischemia. Renal blood flow (RBF), vascular resistance (RVR), oxygen delivery (DO2ren) and consumption (VO2ren), sodium...
Journal of Clinical and Translational Research, 2020
Background: The consequences of acute normovolemic hemodilution (ANH) following different types o... more 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 (P=0.003, P=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 (P=0.02) and NS groups only (P<0.0001, P=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.
Uploads
Papers by Bulent Ergin