The blood lactate/pyruvate equilibrium affair.

The Lactate Shuttle hypothesis is supported by a variety of techniques including mass spectrometry analytics following infusion of carbon-labeled isotopic tracers. However, there has been controversy over whether lactate tracers measure lactate (L) or pyruvate (P) turnover. Here, we review the analytical errors, use of inappropriate tissue and animal models, failure to consider L and P pool sizes in modeling results, inappropriate tracer and blood sampling sites, and failure to anticipate roles of heart and lung parenchyma on L⇔P interactions. With support from magnetic resonance spectroscopy (MRS) and immunocytochemistry, we conclude that carbon-labeled lactate tracers can be used to quantitate lactate fluxes.

Induction of scaffold angiogenesis by recipient vasculature precision micropuncture.

The success of engineered tissues continues to be limited by time to vascularization and perfusion. Here, we studied the effects of precision injury to a recipient macrovasculature in promoting neovessel formation in an adjacently placed scaffold. Segmental 60 µm diameter micropunctures (MP) were created in the recipient rat femoral artery and vein followed by coverage with a simple collagen scaffold. Scaffolds were harvested at 24, 48, 72, and 96 h post-implantation for detailed analysis. Those placed on top of an MP segment showed an earlier and more robust cellular infiltration, including both endothelial cells (CD31) and macrophages (F4/80), compared to internal non-micropunctured control limbs (p < 0.05). At the 96-hour timepoint, MP scaffolds demonstrated an increase in physiologic perfusion (p < 0.003) and a 2.5-fold increase in capillary network formation (p < 0.001). These were attributed to an overall upsurge in small vessel quantity. Furthermore, MP positioned scaffolds demonstrated significant increases in many modulators of angiogenesis, including VEGFR2 and Tie-2 despite a decrease in HIF-1α at all timepoints. This study highlights a novel microsurgical approach that can be used to rapidly vascularize or inosculate contiguously placed scaffolds and grafts. Thereby, offering an easily translatable route towards the creation of thicker and more clinically relevant engineered tissues.

A New Method Involving Percutaneous Application in the Treatment of Deep Venous Insufficiency: An Experimental Study With Internal Compression Therapy in a Porcine Model.

INTRODUCTION: To study the efficiency of internal compression therapy (ICT), a new and promising method of treatment for deep venous insufficiency, how that efficiency is achieved, and its potential side-effects, in a porcine model. MATERIAL AND METHODS: The femoral vein diameters of 4 pigs were first measured. ICT was then applied such as to reduce the diameter of these veins by 50%. The femoral vein diameters of 2 pigs were re-measured after 1 month. The femoral vein and its surrounding tissue were excised for immunohistopathological and genetic examination. The same procedures were applied to the remaining 2 pigs 3 months subsequently. Collagen I and IV immunohistochemical staining and Masson's trichrome and Alcian blue histochemical staining were applied during immunohistopathological examination. Collagen I, III, and IV and connective tissue growth factor (CTGF) mRNA expressions were examined for genetic examination. RESULTS: The femoral vein diameters decreased by approximately 50% after ICT application. This decrease persisted after the first and third months. Histopathological examination revealed loose connective tissue around the venous tissue after the operation, particularly in the third month, together with perivascular fibrosis and increased collagen in connective tissue. No difference was observed between regions with and without ICT application in terms of mucinous degeneration, an indicator of tissue injury, during Alcian blue staining. Genetic examination revealed an increase in collagen I and IV and CTGF mRNA expression in perivascular tissue resulting from ICT application. CONCLUSION: ICT is effective both in terms of creating a durable tissue around the vein and of increasing collagen tissue and stimulating fibrosis, and has no deleterious side-effects on tissue.

Ischemic Preconditioning Improves Microvascular Endothelial Function in Remote Vasculature by Enhanced Prostacyclin Production.

BACKGROUND The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. METHODS AND RESULTS A total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand-grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced (P<0.05) the remote vasodilator response to intra-arterial acetylcholine in the leg at 5 and 90 minutes after application. The enhanced response was associated with a 6-fold increase (P<0.05) in femoral venous plasma prostacyclin levels and with a transient increase (P<0.05) in arterial plasma levels of brain-derived neurotrophic factor and vascular endothelial growth factor. In contrast, hand-grip exercise did not influence remote microvascular function. CONCLUSIONS These findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral-mediated potentiation of prostacyclin formation.

A Novel Model of Balloon Angioplasty Injury in Rat Arteriovenous Fistula.

BACKGROUND: There are very few animal models of balloon angioplasty injury in arteriovenous fistula (AVF), hindering insight into the pathophysiologic processes following angioplasty in AVF. The objective of the study was to develop and characterize a rat model of AVF angioplasty injury. METHODS: Balloon angioplasty in 12- to 16-week-old Sprague-Dawley rats was performed at the arteriovenous anastomosis 14 days post-AVF creation with a 2F Fogarty balloon catheter. Morphometry and protein expression of endothelial nitric oxide synthase (eNOS), monocyte-chemoattractant protein-1 (MCP-1), alpha-smooth muscle actin (α-SMA), CD68 (macrophage marker), and collagen expression in AVFs with and without angioplasty were assessed. RESULTS: In AVFs with angioplasty versus without angioplasty: (1) angioplasty increased AVF-vein and artery intimal hyperplasia, (2) angioplasty decreased eNOS protein expression in AVF-vein and artery at 21 days post-AVF creation and remained decreased in the AVF-vein angioplasty group at 35 days, (3) angioplasty increased AVF-vein and artery α-SMA expression within the intimal region at 35 days, (4) angioplasty increased the expression of AVF-vein MCP-1 at 21 days and CD68 at 21 and 35 days, and (5) angioplasty increased AVF-vein and artery collagen expression at 35 days. CONCLUSION: Our findings describe a reproducible rat model to better understand the pathophysiologic mechanisms that ensue following AVF angioplasty.

Oral Intake of EPA:DHA 6:1 by Middle-Aged Rats for One Week Improves Age-Related Endothelial Dysfunction in Both the Femoral Artery and Vein: Role of Cyclooxygenases.

In humans, aging is associated with endothelial dysfunction and an increased risk of venous thromboembolism. Although intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 6:1 by old rats improved the endothelial dysfunction in arteries, the impact on veins remains unclear. Eight-month-old male Wistar rats were either untreated or orally administered corn oil, EPA:DHA 1:1, or EPA:DHA 6:1 (500 mg/kg/d) for seven days. Vascular reactivity was studied by myography. In middle-aged femoral artery rings, acetylcholine caused a partial relaxation at low concentrations and a contractile response at high concentrations, whereas in the old femoral vein only a partial relaxation was observed. The EPA:DHA 6:1 treatment blunted the contractile response to acetylcholine in the middle-aged femoral artery and both EPA:DHA 6:1 and 1:1 increased the relaxation to acetylcholine in the old femoral vein. No such effects were observed with corn oil. Both the non-selective cyclooxygenase inhibitor indomethacin and the COX-1 inhibitor SC-560 increased the relaxation to acetylcholine in the middle-aged femoral artery whereas the COX-2 inhibitor NS-398 increased that in the middle-aged femoral vein. In conclusion, our results indicate that aging is associated with an endothelial dysfunction in the femoral artery and vein, which can be improved by EPA:DHA 6:1 treatment-most likely via a cyclooxygenase-dependent mechanism.

Association between Galectin-3 levels within central and peripheral venous blood, and adverse left ventricular remodelling after first acute myocardial infarction.

Our study investigates association between Galectin-3 levels and adverse left ventricular remodelling (LVR) at six months. Fifty-seven patients following first acute myocardial infarction (AMI) were enrolled in this study and blood samples collected on day 1 from the femoral vein and artery, the right atrium near the coronary sinus and the aortic root, and on day 30, from the cubital vein. Patients with LVESV ≥20% at six months, were included in the LVR group. On day 1, Galectin-3 plasma levels in the femoral vein (10.34 ng/ml ± 3.81 vs 8.22 ng/ml ± 2.34, p = 0.01), and near coronary sinus (10.7 ng/ml ± 3.97 vs 8.41 ng/ml ± 2.56, p = 0.007) were higher in the LVR group. Positive correlations between Galectin-3 levels from aortic root and coronary sinus, aortic root and femoral vein, and coronary sinus and femoral vein, were observed in both groups. On day 30, Galectin-3 concentration in the cubital vein was an independent risk factor of LVR six months post-AMI, demonstrating 1.5-fold increased risk. Day-30 Galectin-3 also showed positive correlations with echocardiography parameters indicative of diastolic and systolic dysfunction. Determining Galectin-3 plasma concentration on day 30 following AMI could have beneficial prognostic value in predicting LVR.

Lactate production without hypoxia in skeletal muscle during electrical cycling: Crossover study of femoral venous-arterial differences in healthy volunteers.

BACKGROUND: Aim of the study was to compare metabolic response of leg skeletal muscle during functional electrical stimulation-driven unloaded cycling (FES) to that seen during volitional supine cycling. METHODS: Fourteen healthy volunteers were exposed in random order to supine cycling, either volitional (10-25-50 W, 10 min) or FES assisted (unloaded, 10 min) in a crossover design. Whole body and leg muscle metabolism were assessed by indirect calorimetry with concomitant repeated measurements of femoral venous-arterial differences of blood gases, glucose, lactate and amino acids. RESULTS: Unloaded FES cycling, but not volitional exercise, led to a significant increase in across-leg lactate production (from -1.1±2.1 to 5.5±7.4 mmol/min, p<0.001) and mild elevation of arterial lactate (from 1.8±0.7 to 2.5±0.8 mM). This occurred without widening of across-leg veno-arterial (VA) O2 and CO2 gaps. Femoral SvO2 difference was directly proportional to VA difference of lactate (R2 = 0.60, p = 0.002). Across-leg glucose uptake did not change with either type of exercise. Systemic oxygen consumption increased with FES cycling to similarly to 25W volitional exercise (138±29% resp. 124±23% of baseline). There was a net uptake of branched-chain amino acids and net release of Alanine from skeletal muscle, which were unaltered by either type of exercise. CONCLUSIONS: Unloaded FES cycling, but not volitional exercise causes significant lactate production without hypoxia in skeletal muscle. This phenomenon can be significant in vulnerable patients' groups.

Effect of miR-495 on lower extremity deep vein thrombosis through the TLR4 signaling pathway by regulation of IL1R1.

Lower extremity deep vein thrombosis (LEDVT), a common peripheral vascular disease caused by a blood clot in a deep vein is usually accompanied by swelling of the lower limbs. MicroRNAs (miRs) have been reported to play roles in LEDVT. We aimed to investigate the effect of miR-495 on LEDVT via toll-like receptor 4 (TLR4) signaling pathway through interleukin 1 receptor type 1 (IL1R1). LEDVT mouse model was established, and the femoral vein (FV) tissues were collected to detect expressions of miR-495, IL1R1, and TLR4 signaling-related genes. The expressions of both CD31 and CD34 (markers for endothelial progenitor cells) in the FV endothelial cells as well as the proportion of CD31+/CD34+ cells in peripheral blood were measured in order to evaluate thrombosis. The effect of miR-495 on cell viability, cell cycle, and apoptosis was analyzed. IL1R1 was confirmed as the target gene of miR-495. Besides, inhibiting the miR-495 expression could increase IL1R1 expression along with activating the TLR4 signaling pathway. The total number of the leukocytes along with the ratio of weight to length of thrombus in the FV tissue showed an increase. The overexpression of miR-495 could promote FV endothelial cell viability. By injecting agomiR-495 and antagomiR-495 in vivo, the number of leukocytes in the FV tissues and the ratio of weight to length of thrombus were significantly decreased in the mice injected with the overexpressed miR-495, and the IL1R1/TLR4 signaling pathway was inhibited. Collectively, overexpressed miR-495 directly promotes proliferation while simultaneously inhibiting apoptosis of FV endothelial cells, alleviating FV thrombosis by inhibiting IL1R1 via suppression of TLR4 signaling pathway.

Correlation of Caveolin-1 With Vascular Intimal Thickness for Different Locations of Catheter Tips in a Dog Model.

INTRODUCTION: Many studies have reported increased intimal thickness around the catheter tip after catheterization. Caveolin-1 is a protein in the endothelial cell that acts as a shear sensor causing vascular remodeling. This study aimed to elucidate the suitability of different catheter locations and determine the role of caveolin-1 in canine models. MATERIALS AND METHODS: Tunneled silicone 14.5-F catheters were inserted into the left jugular vein and right femoral vein in 8 dogs. The dogs were separated into 2 groups by catheter location and were followed up for 28 days. All dogs underwent extracorporeal circulation 3 times a week. After animal sacrifice, histological and immunohistochemical assays were performed to measure specific cell populations. RESULTS: There were higher catheter dysfunction rates and lower blood flow rates in the right femoral vein group compared to the left jugular vein group. There was intimal hyperplasia around the catheter tip in both groups with no significant difference between the two groups. There were caveolin-1 expression in the intimal layer of venous wall around the catheter tip location sites in both groups. CONCLUSIONS: These findings indicate that different catheter tip locations may influence catheter function and specific targeting of caveonlin-1 could be a strategy of possible future novel therapies for catheter-related vein stenosis.

Injection of Multipotent Mesenchymal Stromal Cells as a Cause of Hemorrhages in the Regional Lymph Nodes: Experimental Study.

Hemorrhagic changes after subcutaneous injection of autologous bone marrow multipotent mesenchymal cells with transfected GFP gene and additionally stained cell membranes to WAG rats in the projection of ligated femoral vein were studied by fluorescent microscopy. Hemorrhages in tissues with experimental acute local venous occlusion were caused by a combination of venous hypertension with inflammation around the foreign body - the ligature used for ligation of the vein. Fibrin found in tissues together with erythrocytes in the hemorrhages could stimulate the formation of granulations and new vessels instead of damaged or thrombosed ones. Multipotent mesenchymal stromal cells and their detritus getting into the regional lymph nodes initiated immune reactions morphologically confirmed by stubborn hypertrophy and hyperplasia of the lymphoid nodules, hemorrhages, and manifest diapedesis of erythrocytes to the organ parenchyma and sinus system.

Arteriovenous Sphingosine-1-Phosphate Differences Across Selected Organs of the Rat.

BACKGROUND/AIMS: Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid that is found in high concentration in plasma. The majority of plasma S1P is transported bound to HDL and albumin. Although the major sources of circulating S1P have been identified, it remains obscure what is the contribution of different organs/tissues to S1P homeostasis in plasma. Answering this question was the major aim of the present study. METHODS: The experiment was performed on male Wistar rats from whom blood samples were taken from either: 1) femoral vein, right ventricle of the heart, and abdominal aorta (n=15) or 2) hepatic vein, portal vein, and abdominal aorta (n=11). Plasma was fractionated by sequential flotation ultracentrifugation and sphingolipids were quantified by a HPLC method. RESULTS: Compared to the mixed venous blood sampled from the right ventricle, total plasma and lipoprotein-depleted plasma (LPDP) concentration of S1P in the arterial blood was lower. On the other hand, the level of S1P increased across the leg both in plasma and LPDP. The concentration of S1P, sphingosine, and sphinganine in the plasma, HDL, and LPDP isolated from the blood taken from the hepatic vein was markedly higher compared to both arterial and portal blood. CONCLUSIONS: We conclude that, in contrast to HDL-bound S1P, albumin-associated S1P is very labile in the circulation. It is degraded in the pulmonary, and to a lesser extent, gastrointestinal circulation, and released across the liver and skeletal muscle. We also conclude that liver is an important source of HDL-bound S1P and circulating free sphingoid bases.

Renal and femoral venous blood flows are regulated by different mechanisms dependent on α-adrenergic receptor subtypes and nitric oxide in anesthetized rats.

Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injection of different doses of vasoactive drugs which act in arterial vascular beds. Anesthetized adult male Wistar rats underwent to right femoral artery and vein cannulation for hemodynamic recordings and infusion of drugs. Doppler flow probes were placed around the left renal artery and vein, and left femoral artery and vein to evaluate the changes in flood flow. Phenylephrine (PHE) injection (α1-adrenergic receptor agonist) elicited vasoconstriction in all arteries and veins. Intravenous prazosin (PZS) (1mg/kg, α1-adrenergic receptor blocker) caused renal artery vasodilation, but not in the other beds. Vasoconstrictor effect of PHE was abolished by PZS in all vascular beds, except in femoral vein. Phentolamine (PTL) injection (1mg/kg, α1/α2-adrenergic receptor blocker) produced renal artery vasodilation with no change in other beds. After PTL, the vasoconstriction evoked by PHE was abolished in all vascular beds. Sodium Nitroprusside (SNP), a nitric oxide donor, elicited vasodilation in all beds, and after PTL but not post PZS injection, SNP enhanced the vasodilatory effect in femoral vein. Our findings suggest that the vasoconstriction in renal and femoral veins is mediated by different subtypes of α-adrenoceptors. The nitric oxide-dependent vasodilation in femoral vein enhances when α2-adrenoceptors are not under stimulation, but not in the other vascular beds investigated.

Intracardiac Hemostasis and Fibrinolysis Parameters in Patients with Atrial Fibrillation.

AIMS: To identify intracardiac hemostasis or fibrinolysis abnormalities, which are associated with atrial fibrillation (AF) and increase the risk of thromboembolism. PATIENTS AND METHODS: Patient group consisted of 24 patients with AF and control group included 14 individuals with other supraventricular tachycardia undergoing transcatheter radiofrequency ablation. Blood samples were drawn from the femoral vein (FV), left atrium (LA), and left atrial appendage (LAA) before the ablation procedure. Fibrinogen, factor VIII (FVIII) and factor XIII activity, von Willebrand factor (VWF) antigen, thrombin-antithrombin (TAT) complex, quantitative fibrin monomer (FM), plasminogen, α2-plasmin inhibitor, plasmin-α2-antiplasmin (PAP) complex, PAI-1 activity, and D-dimer were measured from all samples. RESULTS: Levels of FVIII and VWF were significantly elevated in the FV and LA of AF patients as compared to controls. TAT complex, FM, PAP complex, and D-dimer levels were significantly elevated in the LA as compared to FV samples in case of both groups, indicating a temporary thrombotic risk associated with the catheterization procedure. CONCLUSIONS: None of the investigated hemostasis or fibrinolysis parameters showed significant intracardiac alterations in AF patients as compared to non-AF controls. AF patients have elevated FVIII and VWF levels, most likely due to endothelial damage, presenting at both intracardiac and systemic level.

Initial Stages of Angiogenesis after Acute Experimental Local Venous Outflow Disturbances and Application of Cell Technologies.

The initial stages of angiogenesis in rats after transcutaneous injection of autologous bone marrow multipotent mesenchymal stromal cells transfected with GFP gene and stained cell membranes in the projection of ligated femoral vein were studied by fluorescent light and confocal laser microscopy. Large clusters of brightly fluorescing elongated fibroblast-like cells were seen in the paravasal tissue and in the postoperative scar and signs of angiogenesis were noted as soon as in 4 days. The injected cells not only formed new vessels, but also integrated into vessels formed by host cells. Some injected cells were phagocytizied by macrophages and the latter started to fluoresce due to the presence of the membrane dye. These macrophages within the specified period appeared in the regional inguinal lymph nodes where they formed clusters in the lymphoid parenchyma of the cortical substance.

Prostanoids counterbalance the synergism between endothelin-1 and angiotensin II in mesenteric veins of trained rats.

Exercise-induced adaptations of the modulating mechanisms that influence the angiotensin (Ang II) responses assume different features depending on the venous bed. In femoral veins, exercise mobilizes vasodilator prostanoids to cooperate with NO in order to maintain reduced Ang II responses. On the other hand, exercise's influence on the Ang II responses in veins that drain blood from the mesenteric region has been poorly described. Therefore, the present study aimed to identify the effects of a single bout of exercise, as well as exercise training, on the Ang II responses in mesenteric veins. The present study also aimed to investigate the involvement of prostanoids, NO and ET-1 in eventual exercise-induced modifications in these veins. To this end, mesenteric veins taken from resting-sedentary, exercised-sedentary, resting-trained and exercised-trained animals were studied in organ baths. In addition, the mRNA expression of prepro-endothelin-1 (ppET-1), as well as that of the ETA and ETB receptors, were quantified by real-time PCR in these veins. The results show that, either in absence or in presence of L-NAME, the Ang II responses were not different between groups. In the presence of indomethacin, higher Ang II responses were observed in the resting-trained animals than in the resting-sedentary animals. This difference, however, disappeared when L-NAME, BQ-123 or BQ-788 were added during incubation. In addition, no differences in ppET-1, ETA or ETB mRNA expression were observed between groups. Furthermore, in the presence of PD123,319, the Ang II responses in the exercised-sedentary animals were higher than those in the resting-sedentary animals. In conclusion, exercise training mobilizes endothelin-1 (ET-1) to reinforce the Ang II-induced responses mainly through ETA activation. On the other hand, vasodilator prostanoids are mobilized to act in parallel with NO in order to counterbalance the Ang II responses that have been potentiated by ET-1 in these trained animals.

Regional tissue oximetry reflects changes in arterial flow in porcine chronic heart failure treated with venoarterial extracorporeal membrane oxygenation.

Venoarterial extracorporeal membrane oxygenation (VA ECMO) is widely used in treatment of decompensated heart failure. Our aim was to investigate its effects on regional perfusion and tissue oxygenation with respect to extracorporeal blood flow (EBF). In five swine, decompensated low-output chronic heart failure was induced by long-term rapid ventricular pacing. Subsequently, VA ECMO was introduced and left ventricular (LV) volume, aortic blood pressure, regional arterial flow and tissue oxygenation were continuously recorded at different levels of EBF. With increasing EBF from minimal to 5 l/min, mean arterial pressure increased from 47+/-22 to 84+/-12 mm Hg (P<0.001) and arterial blood flow increased in carotid artery from 211+/-72 to 479+/-58 ml/min (P<0.01) and in subclavian artery from 103+/-49 to 296+/-54 ml/min (P<0.001). Corresponding brain and brachial tissue oxygenation increased promptly from 57+/-6 to 74+/-3 % and from 37+/-6 to 77+/-6 %, respectively (both P<0.01). Presented results confirm that VA ECMO is a capable form of heart support. Regional arterial flow and tissue oxygenation suggest that partial circulatory support may be sufficient to supply brain and peripheral tissue by oxygen.

Leiomiosarcoma intraluminal de vena femoral común / Intraluminal leiomyosarcoma of the common femoral vein

No disponible

Enfermedad quística subadventicial en vena femoral común / Subadventitial cystic disease of common femoral vein

No disponible

Hepatic erythropoietin response in cirrhosis.

BACKGROUND: Erythropoietin (EPO) is produced in the liver during fetal life, but after birth the production shifts to the kidneys. The liver maintains a production capacity of 10% of the total EPO-production, but can be up-regulated to 100%. Previous studies have demonstrated both elevated and reduced concentrations of EPO in cirrhosis. Increased EPO concentrations could be expected due to anemia, hypoxia, renal hypoperfusion, or EPO-mediated hepatoprotective mechanisms. In contrast, poor hepatic production capacity may cause reduced EPO concentrations in cirrhosis. In the present paper we aimed to study hepatic and renal venous concentrations of EPO in relation to the severity of the disease. MATERIALS AND METHODS: We included 24 patients with alcoholic cirrhosis and eight age-matched healthy controls. All had a full catheterization performed with the determination of EPO concentrations in the hepatic, renal and femoral veins and artery. All patients were clinically, biochemically, and hemodynamically characterized. RESULTS: The median arterial EPO concentrations in the cirrhotic patients and controls were 7.1 mIU/mL (range 3.5-179) and 7.2 mIU/mL (range 3.8-15.3), respectively. In the patient group we found no significant correlations to stage of disease of hemodynamic derangement. CONCLUSION: We found no significant differences in EPO concentrations across the liver, kidney, or peripheral circulation in the patient or control groups; and no significant correlations to clinical, biochemical, or hemodynamic characteristics. This suggests that hepatic EPO synthesis is not enhanced in cirrhosis, but larger scale studies are needed to clarify this question.