Blood Volume Expansion Research Articles

Influence of factor XIII activity on post-operative transfusion in congenital cardiac surgery-A retrospective analysis.

ObjectivesCoagulation factor XIII (FXIII) plays a key role in fibrin clot stabilization—an essential process for wound healing following cardiothoracic surgery. However, FXIII deficiency as a risk for post-operative bleeding in pediatric cardiac surgery involving cardiopulmonary bypass (CPB) for congenital heart disease (CHD) is controversially discussed. Thus, as primary outcome measures, we analyzed the association of pre-operative FXIII activity and post-operative chest tube drainage (CTD) loss with transfusion requirements post-operatively. Secondary outcomes included the influence of cyanosis and sex on transfusion.MethodsOur retrospective analysis (2009–2010) encompassed a single center series of 76 cardio-surgical cases with CPB (0–17 years, mean age 5.61 years) that were post-operatively admitted to our pediatric intensive care unit (PICU). The observational period was 48 hours after cardiac surgery. Blood cell counts and coagulation status, including FXIII activity were routinely performed pre- and post-operatively. The administered amount of blood products and volume expanders was recorded electronically, along with the amount of CTD loss. Uni- and multivariate logistic regression analysis was performed to calculate the associations (odds ratios) of variables with post-operative transfusion needs.ResultsFXIII activities remained stable following CPB surgery. There was no association of pre- and post-operative FXIII activities and transfusion of blood products or volume expanders in the first 48 hours after surgery. Similarly, FXIII showed no association with CTD loss. Cyanosis and female sex were associated with transfusion rates.ConclusionsAlthough essentially involved in wound healing and clotting after surgery, FXIII activity does not serve as a valid predictor of post-operative transfusion need.

Pharmacotherapy for postural tachycardia syndrome.

Postural tachycardia syndrome (POTS) is a disorder characterized by the presence of orthostatic symptoms (including lightheadedness, palpitations, nausea, dyspnea, and tremulousness) as well as excessive upright tachycardia. POTS predominantly affects women of childbearing age. Treating POTS involves a multi-faceted approach using non-pharmacological and pharmacological interventions. There are no pharmacological treatments that are currently United States Food and Drug Administration (FDA) approved for POTS due to lack of randomized controlled trials. Yet, several medications can improve POTS symptoms and are supported by small prospective studies or retrospective case series. Drugs that are most commonly used for POTS target the following mechanisms 1) blood volume expansion, 2) reduction of heart rate, 3) peripheral vasoconstriction and 4) sympatholysis. Pharmacological approaches can also be used to target specific symptoms including "brain fog," fatigue, sleep, and depression. This review outlines pharmacological approaches for treating POTS and summarizes evidence supporting each treatment approach.

Activated NO pathway in uterine arteries during pregnancy in an IUGR rat model.

Insufficient development of the uteroplacental circulation may contribute to the development of intrauterine growth restriction (IUGR). We developed a rat model of IUGR by administering a low-Na+ diet. This diet reduces maternal blood volume expansion and uteroplacental perfusion. We hypothesized that an impaired endothelial function in radial arteries decreases vasorelaxation and lowers placental perfusion in this IUGR model. The objective was to assess radial uterine artery responses to vasoactive agents in the IUGR model versus controls. The vasoactive agents included phenylephrine and carbachol, use of a pressurized artery myograph, in the absence or presence of inhibitors of nitric oxide (NO) synthase [ N-nitro-l-arginine methyl ester (l-NAME)], cyclooxygenase (Ibuprofen), and endothelium-dependent hyperpolarization {apamin/1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole}, allowing better characterization of the mechanism implicated in endothelium-dependent relaxation. The results show that 1) the diameter of uterine radial arteries was significantly decreased in the IUGR group; 2) sensitivity to phenylephrine was reduced in IUGR arteries, which could be returned to control group values by inhibition of NO production; 3) the relaxation response to carbachol was increased in IUGR rats, principally mediated by endothelium-dependent hyperpolarization in both groups; 4) NO synthase inhibition by l-NAME decreased the maximum relaxation to carbachol only in the IUGR group; and 5) relaxation response to NO donors is increased in IUGR compared with control radial arteries. Contrary to the hypothesis, results in the IUGR model indicate that the NO pathway is activated in radial uterine arteries, most likely in compensation for the reduction in blood uteroplacental perfusion. NEW & NOTEWORTHY In contrast to genetic or surgical models of intrauterine growth restriction, the diet-induced model of reduced maternal volume expansion shows the nitric oxide pathway to be activated in the uterine artery, possibly from increased shear stress and/or placental factors.

Hemodynamic and Body Fluid Response to Water Ingestion

Despite a paucity of information regarding the hemodynamic changes associated with moderate fluid ingestion, the popular, unsubstantiated recommendation for most adults to ingest 8 x 8 ounce glasses of water daily (1888 mL) remains prevalent. PURPOSE: The purpose of this study was to determine the hemodynamic and body fluid changes associated with consuming water at temperatures of 4° C & 37° C and two volumes of 7 & 21 mL/kg. METHODS: 10 subjects (age 22.3 ± 1.3 yr, ht. 1.74 ± .15 m., body mass(bm), 75.1 ± 18.5 kg, 4♂) reported to the lab in a euhydrated state and refrained from ingestion of food and beverage (except water) for 10 hrs and no water 2 hours pre- trial. 30 minutes of rest preceded venipuncture for hematocrit (H), plasma specific gravity (PSG), and plasma density (PD) analyzed by digital refractometry. Hemodynamic values of heart rate (HR), stroke volume (SV) and cardiac output (Q) were obtained by a non-invasive impedance cardiography system. All measures were obtained pre-water ingestion (PRE) and at 20 minute intervals following water ingestion (T1, T2, & T3). Immediately following the PRE, subjects ingested C7, C21, H7 or H21 with the volume calculated from individual bm at a mean of 526 and 1577 mL for 7 and 21 trials, respectively. Subjects served as their own control in the randomized assignment of trials. RESULTS: Statistical analysis by ANOVA was applied to these data and revealed NSD (p>.05) among all trials. Mean values for all four trials are depicted in the following table:Table: No title available.CONCLUSION: The ingestion of water in volumes and temperatures mimicking current practices among many adults results in minimal expansion of blood volume or changes in hemodynamic function. Apparently, consuming considerable water without excessive loss of fluid from either environmental conditions or exercise induced temperature regulation, is safe with no adverse impact on non-exercising individuals.

Limited value of end-expiratory inferior vena cava diameter to predict fluid responsiveness impact of intra-abdominal pressure.

We sought to determine the diagnostic ability of the end-expiratory inferior vena cava diameter (IVCEE) to predict fluid responsiveness (FR) and the potential confounding effect of intra-abdominal pressure (IAP). In this multicenter study, 540 consecutive ventilated patients with shock of various origins underwent an echocardiographic assessment by experts. The IVCEE, velocity time integral (VTI) of the left ventricular outflow tract (LVOT) and intra-abdominal pressure (IAP) were measured. Passive leg raising (PLR) was then systematically used to perform a reversible central blood volume expansion. FR was defined by an increase in LVOT VTI ≥10% after 1min of PLR. Since IVCEE was not obtained in 117 patients (22%), 423 were studied (septic shock: 56%), 129 of them (30%) having elevated IAP (≥12mmHg) and 172 of them (41%) exhibiting FR. IVCEE≤13mm predicted FR with a specificity of at least 80% in 62 patients (15%), while IVCEE≥25mm predicted the absence of FR with a specificity of at least 80% in 61 patients (14%). In the remaining 300 patients (71%), the intermediate value of IVCEE did not allow predicting FR. An adjusted relationship between IVCEE and FR was observed while this relationship was less pronounced in patients with IAP≥12mmHg. Measurement of IVCEE in ventilated patients is moderately feasible and poorly predicts FR, with IAP acting as a confounding factor. IVCEE might add some value to guide fluid therapy but should not be used alone for fluid prediction purposes.

Hemodynamic and Electrocardiographic Aspects of Uncomplicated Singleton Pregnancy.

Pregnancy is associated with significant changes in maternal hemodynamics, which are triggered by profound systemic vasodilation and mediated through the autonomic nervous system as well as the renin-angiotensin-aldosterone system. Vascular function changes to help accommodate an increase in intravascular volume due to blood volume expansion associated with pregnancy while maintaining the efficiency of ventricular-arterial coupling and diastolic perfusion pressure. The heart undergoes physiological (eccentric) hypertrophy due to increased volume load and cardiac stroke work, whereas the functional change of the left ventricle remains controversial. There are changes in cardiac electrical activity during pregnancy which can be detected in the electrocardiogram that are not related to disease. Sympathetic activation is a common phenomenon during uncomplicated pregnancy and may be a compensatory mechanism induced by profound systemic vasodilation and a decrease in mean arterial pressure. Despite marked sympathetic activation, vasoconstrictor responsiveness is blunted during uncomplicated pregnancy. There are race and ethnic differences in maternal hemodynamic adaptations to uncomplicated pregnancy, which may be attributed to differences in socioeconomic status or in prevalence rates of cardiovascular risk factors.

The prognostic importance of the heart function in sepsis and septic shock: a Dedalus or a window of opportunities?

Sepsis is an infection-related clinical condition characterized by severe systemic inflammation, potentially evolving in multi-organ failure through a number of pathophysiological mechanisms. While sepsis is a relatively infrequent disease, it is a world-wide growing and challenging medical issue (1-3), both due to high mortality rate in the short and mid-term follow-ups, and to high costs of medical management (4,5). Hemodynamic instability and sustained hypotension with systemic hypoperfusion not responding to blood volume expansion are the hallmarks of the sepsis-related shock, or septic shock. In sepsis, refractory cardiovascular failure is a frequent cause of fatal events, and myocardial injury can be found in approximately 50% of the patients in necropsy findings (6). Therefore, one cannot infer that sepsis or septic shock is equivalent to myocardial dysfunction.

The alliance with expanding blood volume and correcting anemia is an effective therapeutic measure for the adult anemia patients of acute cerebral infarction

ABSTRACTPurpose/aim of the study: Various factors are believed to be involved in the etiology of cerebral infarction. Anemia has been shown to deteriorate in association with ischemic stroke. However, the exact clinical association between anemia and ischemic stroke still remains unclear. We evaluated the clinical features of adult anemia patients with acute cerebral infarction and seek a better treatment different from the other causes of cerebral infarction, and to provide a reference for the diagnosis and treatment of these anemia patients with acute cerebral infarction.Methods: Thirty-two adult patients of acute cerebral infarction with anemia were included in this study. A primary discharge diagnosis of acute cerebral infarction with anemia was done, and all subjects were evaluated as retrospective data. The clinical features were analyzed. A chi-square test was used to analyze the associations between different variables. Therapeutic interventions and outcomes were analyzed under t-test, compared between the two groups.Results: The NIHSS score in the patients with the administration of EBV/CA (Expanding blood volume and correcting anemia) more lowed than Non-EBV/CA in 7 days and 14 days after initial hospitalization. The mRS score in the patients with the administration of EBV/CA also more lowed than Non-EBV/CA in 14 days. Moreover, the correlation between Hb-serum-level and NIHSS scores in the time of initial hospitalization is negative significantly.Conclusions: Anemia is associated with increased neuronal damage and deterioration of acute cerebral infarction in the adults. Expanding blood volume and correcting anemia are effective therapeutic measures in the adult patients of acute cerebral infarctions with anemia.

The influence of prenatal exercise and pre-eclampsia on maternal vascular function.

During healthy pregnancy, the cardiovascular system undergoes diverse adaptations to support adequate transfer of oxygen and nutrients from mother to fetus. In order to accommodate the large expansion of blood volume and associated cardiac output, the structure, mechanics, and function of the arteries are altered. Specifically, in healthy pregnancy there is a remodeling of arteries (increased angiogenesis and vasodilation), a generalized reduction in arterial stiffness (increased compliance), and an enhanced endothelial function. The development of pregnancy complications, specifically pre-eclampsia, is associated with poor placentation (decreased angiogenesis), increased arterial stiffness, and vascular dysfunction (reduced endothelial function). Many of the positive adaptations that occur in healthy pregnancy are enhanced in response to chronic exercise. Specifically, placental angiogenesis and endothelial function have been shown to improve to a greater extent in women who are active during their pregnancy compared with those who are not. Prenatal exercise may be important in helping to reduce the risk of vascular dysfunction in pregnancy. However, our knowledge of the vascular adaptations resulting from maternal exercise is limited. This review highlights maternal vascular adaptations occurring during healthy pregnancy, and contrasts the vascular maladaptation associated with pre-eclampsia. Finally, we discuss the role of prenatal exercise on vascular function in the potential prevention of vascular complications associated with pre-eclampsia.

27-Hydroxycholesterol induces hematopoietic stem cell mobilization and extramedullary hematopoiesis during pregnancy.

Extramedullary hematopoiesis (EMH) is induced during pregnancy to support rapid expansion of maternal blood volume. EMH activation requires hematopoietic stem cell (HSC) proliferation and mobilization, processes that depend upon estrogen receptor α (ERα) in HSCs. Here we show that treating mice with estradiol to model estradiol increases during pregnancy induced HSC proliferation in the bone marrow but not HSC mobilization. Treatment with the alternative ERα ligand 27-hydroxycholesterol (27HC) induced ERα-dependent HSC mobilization and EMH but not HSC division in the bone marrow. During pregnancy, 27HC levels increased in hematopoietic stem/progenitor cells as a result of CYP27A1, a cholesterol hydroxylase. Cyp27a1-deficient mice had significantly reduced 27HC levels, HSC mobilization, and EMH during pregnancy but normal bone marrow hematopoiesis and EMH in response to bleeding or G-CSF treatment. Distinct hematopoietic stresses thus induce EMH through different mechanisms. Two different ERα ligands, estradiol and 27HC, work together to promote EMH during pregnancy, revealing a collaboration of hormonal and metabolic mechanisms as well as a physiological function for 27HC in normal mice.

Polyethylene Glycol Camouflaged Earthworm Hemoglobin.

Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris. LtEc is an extremely stable protein complex, resistant to autoxidation, and capable of transporting O2 to tissue when transfused into mammals. These characteristics render LtEc a promising candidate for the development of the next generation HBOCs. LtEc has a short half-life in circulation, limiting its application as a bridge over days, until blood became available. Conjugation with polyethylene glycol (PEG-LtEc) can extend LtEc circulation time. This study explores PEG-LtEc pharmacokinetics and pharmacodynamics. To study PEG-LtEc pharmacokinetics, hamsters instrumented with the dorsal window chamber were subjected to a 40% exchange transfusion with 10 g/dL PEG-LtEc or LtEc and followed for 48 hours. To study the vascular response of PEG-LtEc, hamsters instrumented with the dorsal window chamber received multiple infusions of 10 g/dL PEG-LtEc or LtEc solution to increase plasma LtEc concentration to 0.5, then 1.0, and 1.5 g/dL, while monitoring the animals’ systemic and microcirculatory parameters. Results confirm that PEGylation of LtEc increases its circulation time, extending the half-life to 70 hours, 4 times longer than that of unPEGylated LtEc. However, PEGylation increased the rate of LtEc oxidation in vivo. Vascular analysis verified that PEG-LtEc showed the absence of microvascular vasoconstriction or systemic hypertension. The molecular size of PEG-LtEc did not change the colloid osmotic pressure or blood volume expansion capacity compared to LtEc, due to LtEc’s already large molecular size. Taken together, these results further encourage the development of PEG-LtEc as an O2 carrying therapeutic.

Longitudinal study of vascular structure and function during normal pregnancy.

To examine alterations in maternal vascular structure and function during normal pregnancy. We assessed brachial and central blood pressure, pulse-wave velocity and augmentation index (by pulse-wave analysis and applanation tonometry), common carotid artery structure (by ultrasonography) and endothelial function in the brachial artery (by postischemic hyperemia-induced flow-mediated vasodilatation by glyceryl trinitrate) and in the forearm skin microcirculation (by laser Doppler perfusion imaging during iontophoretic administration of acetylcholine and sodium nitroprusside) in 52 healthy nulliparous women at 14, 24 and 34 weeks' gestation, and at 9 months postpartum. During pregnancy, brachial and central systolic and diastolic blood pressures initially decreased but subsequently increased (all P < 0.05). Flow-mediated vasodilatation in the brachial artery increased during early pregnancy (P < 0.05), whereas non-specific vasodilatation by glyceryl trinitrate decreased (P < 0.01), indicating improved endothelial function. Thus, endothelial function index (forearm blood flow/glyceryl trinitrate) increased during pregnancy (0.30 ± 0.18 in the non-pregnant state at 9 months postpartum and 0.51 ± 0.19, 0.61 ± 0.39 and 0.49 ± 0.30 in the first, second and third trimesters, respectively) (P < 0.001). Endothelium-dependent skin microvascular reactivity to acetylcholine also increased (P < 0.01). Carotid-femoral pulse-wave velocity decreased during pregnancy (5.88 ± 0.91 m/s in the non-pregnant state and 5.55 ± 0.67, 5.12 ± 0.66 and 5.62 ± 0.74 m/s in the first, second and third trimesters, respectively) (P < 0.001). During normal pregnancy, the blood volume expansion necessary for sufficient fetal growth is accommodated by early and marked changes in the matvascular system. This seems to be dependent on normal adaptive endothelial and vascular function. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Application of a Multi-Marker Approach to Assess Vitamin B12 Status at the End of the First Trimester of Pregnancy

Background:During pregnancy, vitamin B12 (B12) utilisation increases, with deficiency being associated with adverse outcomes (Murphy 2007, VanderJagt 2011). It remains unclear however at what level vitamin B12 status becomes detrimental, and the correlation with fetal harm.Establishing B12 status during pregnancy is complicated by physiological changes such as haemodilution due to expanded blood volume, altered renal function, alterations in the vitamin B12 -binding proteins and transfer of materno-fetal B12 yet laboratories typically rely on the total abundance of B12 in serum (serum B12) asthe sole laboratory status indicator, interpreting results against reference range cut offs derived from non-pregnant populations, including men.Serum B12 assays measure the sum of holohaptocorrin and holotranscobalamin (holoTC). Other markers of B12 status are also available and are increasingly being adopted: holoTC (active B12) accounts 6-20% of bound B12, which is the only form of B12 presented for cellular uptake and used to satisfy metabolic demand; methylmalonic acid (MMA) is a by-product of methylmalonyl-CoA metabolism, the concentration of which in serum correlates inversely with tissue B12 utilisation.Methods:Over a 2 monthperiod in 2015 we used an extended panel of laboratory tests consisting of serum B12, holoTC, and MMA to determine B12 status, and assess appropriateness of our assay reference ranges, in 100 pregnant women with normal renal function at the end of the first trimester.Laboratory AnalysisSerum B12 and holoTC were determined by an Abbott Architect analyzer. The serum B12 assay has a reference range of 187 - 883 ng/L. The holoTC assay has ²10% cross-reactivity from B12-binding proteins haptocorrin and apotranscobalamin. Values >128 pmol/L are above the dynamic assay range. In our laboratory holoTC results <25 pmol/L are defined as deficient and those >70 pmol/L as replete. Results 25-70 pmol/L are classified as indeterminate and a serum MMA assay subsequently performed (Sobczyńska-Malefora A et al 2014). We determined serum MMA using a Gerstel Multipurpose Sampler coupled to a liquid chromatography tandem mass spectrometer with electrospray ionization with results >270 nmol/L considered indicative of suboptimal B12 status (Harrington DJ 2016).Results:All three assays, figure 3, were performed for 92 women (insufficient sample available n=8).HoloTCand MMA results are shown in Table 1. The distribution ofholoTCand MMA concentrations are shown in Figure 1.One woman had a serum B12 below the reference range with a corresponding indeterminate holoTC and normal MMA. This set of results suggests questionable abundance of B12 that has not translated to functional deficiency.One woman had a holoTCconcentration <25pmol/L, however the corresponding serum B12 and MMA were not indicative of sub optimal B12 status. Fourteen women had aholoTC result above the dynamic assay range.Two women had an elevated MMA concentration with corresponding holoTCresults indicating questionable abundance of B12 but serum B12 within our reference limit. This triad of values indicates possible emerging suboptimal B12 status that would have been overlooked if serum B12 had been used in isolation.Discussion:B12 requirement increases in pregnancy and diet alone is unlikely to meet requirements (Murphy et al 2007). Deficiency has a detrimental impact on maternal and infant development and therefore it is useful to explore the relationship between different laboratory markers of B12 status in pregnancy (Ramirez-Velez et al 2016, Siddiqua et al 2014). The comparison of serum B12,holoTC and MMA levels at the end of the first trimester with reference ranges derived from non-pregnant adults suggests that they are broadly applicable.Serum B12 is the least sensitive marker and its use in isolation to assess B12 status is limiting. The application of holoTC and MMA in tandem can reveal previously missed deficient states. Using these markers two women in this small study were identified as possibly deficient although the true significance of a mildly elevated MMA in pregnancy requires further investigation. These data highlight the benefit of adopting a panel of markers ahead of a single test to assess B12 status. Identifying women at the end of the first trimester that may benefit from B12 replacement potentially protects from deficient states. [Display omitted] [Display omitted] [Display omitted] DisclosuresRobinson:Pharmacosmos: Honoraria; Amgen: Honoraria; Novartis: Honoraria.

Volume kinetic evaluation of fluid turnover after oral intake of tap water, lemonade and saline in volunteers.

BackgroundVolume kinetic fluid turnover of three beverages was investigated for the purpose of estimating their rates of absorption and elimination as well as their maximum effect on the blood volume. The results were then used to simulate the effects of ingesting different combinations of these fluids.MethodTen healthy volunteers ingested 0.5 L of tap water, lemonade (90 g/L carbohydrates) and isotonic saline (9 g/L) on different occasions. Venous blood samples for measurement of the blood haemoglobin (Hb), haematocrit and glucose concentrations were collected on 10 occasions over 2 h. A kinetic model based on haemoglobin dilution and urinary excretion was used to estimate the rate of absorption, the blood volume expansion over time, and the rate of elimination. Obtained kinetic data was used to simulate combinations of the three beverages in order to reach a predetermined goal of a 1:1 hydration of the blood volume and peripheral tissues over 6 h.ResultsTap water had the fastest absorption but primarily hydrated peripheral tissues. Maximum hydration was reached after 17 min. Lemonade effectively expanded the blood volume and was absorbed and excreted at a high rate. The maximum hydration from isotonic saline occurred 60 min after ingestion. Slow excretion could make it possible to use saline to prolong the effects of the other two beverages.ConclusionsIt is possible to use the kinetic model to evaluate fluid turnover and compartmental distribution. Composition and timing of fluid intake can be calculated mathematically to meet predetermined goals of hydration and distribution.Trial registrationNCT01360333 Date of registration: 05/23/2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s13102-016-0045-x) contains supplementary material, which is available to authorized users.

Comparative Evaluation of Crystalloid Resuscitation Rate in a Human Model of Compensated Haemorrhagic Shock.

ABSTRACTIntroduction:The most effective rate of fluid resuscitation in haemorrhagic shock is unknown.Methods:We performed a randomized crossover pilot study in a healthy volunteer model of compensated haemorrhagic shock. Following venesection of 15 mL/kg of blood, participants were randomized to 20 mL/kg of crystalloid over 10 min (FAST treatment) or 30 min (SLOW treatment). The primary end point was oxygen delivery (DO2). Secondary end points included pressure and flow-based haemodynamic variables, blood volume expansion, and clinical biochemistry.Results:Nine normotensive healthy adult volunteers participated. No significant differences were observed in DO2 and biochemical variables between the SLOW and FAST groups. Blood volume was reduced by 16% following venesection, with a corresponding 5% reduction in cardiac index (CI) (P < 0.001). Immediately following resuscitation the increase in blood volume corresponded to 54% of the infused volume under FAST treatment and 69% of the infused volume under SLOW treatment (P = 0.03). This blood volume expansion attenuated with time to 24% and 25% of the infused volume 30 min postinfusion. During fluid resuscitation, blood pressure was higher under FAST treatment. However, CI paradoxically decreased in most participants during the resuscitation phase; a finding not observed under SLOW treatment.Conclusion:FAST or SLOW fluid resuscitation had no significant impact on DO2 between treatment groups. In both groups, changes in CI and blood pressure did not reflect the magnitude of intravascular blood volume deficit. Crystalloid resuscitation expanded intravascular blood volume by approximately 25%.

Influence of metabolic dysfunction on cardiac mechanics in decompensated hypertrophy and heart failure

Alterations in energetic state of the myocardium are associated with decompensated heart failure in humans and in animal models. However, the functional consequences of the observed changes in energetic state on mechanical function are not known. The primary aim of the study was to quantify mechanical/energetic coupling in the heart and to determine if energetic dysfunction can contribute to mechanical failure. A secondary aim was to apply a quantitative systems pharmacology analysis to investigate the effects of drugs that target cross-bridge cycling kinetics in heart failure-associated energetic dysfunction. Herein, a model of metabolite- and calcium-dependent myocardial mechanics was developed from calcium concentration and tension time courses in rat cardiac muscle obtained at different lengths and stimulation frequencies. The muscle dynamics model accounting for the effect of metabolites was integrated into a model of the cardiac ventricles to simulate pressure-volume dynamics in the heart. This cardiac model was integrated into a simple model of the circulation to investigate the effects of metabolic state on whole-body function. Simulations predict that reductions in metabolite pools observed in canine models of heart failure can cause systolic dysfunction, blood volume expansion, venous congestion, and ventricular dilation. Simulations also predict that myosin-activating drugs may partially counteract the effects of energetic state on cross-bridge mechanics in heart failure while increasing myocardial oxygen consumption. Our model analysis demonstrates how metabolic changes observed in heart failure are alone sufficient to cause systolic dysfunction and whole-body heart failure symptoms.

The demand for human albumin in Italy.

Human albumin (HA) is a blood plasma protein produced in the liver. It constitutes about 60% of plasma proteins and is a physiological plasma-expander. However, its limited availability and high cost make it essential to define recommendations for its appropriate use, as an alternative to other therapeutic strategies including solutions of crystalloids and non-protein colloids. According to all official recommendations, the choice to use albumin rather than an artificial colloid strictly depends on the clinical situation of the patient1–6. HA is also used in all cases in which there is a contraindication to the use of non-protein colloids7. Based on clinical evidence, the 2009 guidance document of the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI)7 recommends the use of HA in acute conditions, which call for blood volume expansion and maintenance of adequate blood flow, as well as in some chronic conditions of low serum albumin levels. “There are some widely shared and fully agreed indications for the appropriate use of human albumin and indications that are occasionally appropriate, that is, when other criteria are fulfilled”7. In addition, in haemorrhagic shock HA should only be used as a second choice [i.e. when solutions of crystalloids or non-protein colloids (first choice treatment) have already been used at maximum doses without having produced a clinically adequate response] and in cases in which non-protein colloids are contraindicated7.

Retrospective Case Reports of Anemic Pregnant Women Receiving Intravenous Ferric Carboxymaltose: Experience from a Tertiary Hospital in Spain.

Iron deficiency and iron deficiency anemia during pregnancy call for safe treatment options that raise maternal hemoglobin levels and counterbalance iron demand and blood volume expansion while minimizing risks for the growing fetus. This retrospective study describes experience with intravenous ferric carboxymaltose given to pregnant women in a tertiary hospital in Spain. In a 5-year period, 95 pregnant women who had pretreatment hemoglobin <10 g/dL and at least one time of ferric carboxymaltose administration during pregnancy were included. Main outcome measures were week of pregnancy at iron administration, Hb levels before and after treatment, neonatal 5-minute Apgar scores, and birth weight. The majority received one dose of ferric carboxymaltose (1000 mg iron) during advanced pregnancy (median 31 weeks; interquartile range [IQR]: 27; 37 weeks) with minor to no adverse outcomes. Overall, median Hb increased from 8.5 g/dL (8.1; 8.9 g/dL) before treatment to 11.0 g/dL (9.9; 11.7 g/dL) after treatment. Normal Apgar scores were observed in all 97 infants (median birth weights 3560 g, 3270, and 3798 g). Four women received ferric carboxymaltose in the first trimester and twenty-eight during the second trimester without adverse outcomes for mother or child. These cases add to the evidence that ferric carboxymaltose administration during pregnancy is effective and safe.

Systemic hemodynamics in advanced cirrhosis: Concerns during perioperative period of liver transplantation.

Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation (LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow (PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green (ICG) kinetics reflect the patient's functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant (kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT.

Maternal and Fetal Outcomes in Pregnant Women with a Prosthetic Mechanical Heart Valve.

BACKGROUNDPregnancy is associated with several cardiocirculatory changes that can significantly impact underlying cardiac disease. These changes include an increase in cardiac output, sodium, and water retention leading to blood volume expansion, and reductions in systemic vascular resistance and systemic blood pressure. In addition, pregnancy results in a hypercoagulable state that increases the risk of thromboembolic complications.OBJECTIVESThe aim of this study is to assess the maternal and fetal outcomes of pregnant women with mechanical prosthetic heart valves (PHVs).METHODSThis is a prospective observational study that included 100 pregnant patients with cardiac mechanical valve prostheses on anticoagulant therapy. The main maternal outcomes included thromboembolic or hemorrhagic complications, prosthetic valve thrombosis, and acute decompensated heart failure. Fetal outcomes included miscarriage, fetal death, live birth, small-for-gestational age, and warfarin embryopathy. The relationship between the following were observed: – Maternal and fetal complications and the site of the replaced valve (mitral, aortic, or double)– Maternal and fetal complications and warfarin dosage (≤5 mg, >5 mg)– Maternal and fetal complications and the type of anticoagulation administered during the first trimesterRESULTSThis study included 60 patients (60%) with mitral valve replacement (MVR), 22 patients (22%) with aortic valve replacement (AVR), and 18 patients (18%) with double valve replacement (DVR). A total of 65 patients (65%) received >5 mg of oral anticoagulant (warfarin), 33 patients (33%) received ≤5 mg of warfarin, and 2 patients (2%) received low-molecular-weight heparin (LMWH; enoxaparin sodium) throughout the pregnancy. A total of 17 patients (17%) received oral anticoagulant (warfarin) during the first trimester: 9 patients received a daily warfarin dose of >5 mg while the remaining 8 patients received a daily dose of ≤5 mg. Twenty-eight patients (28%) received subcutaneous (SC) heparin calcium and 53 patients (53%) received SC LMWH (enoxaparin sodium). Prosthetic valve thrombosis occurred more frequently in patients with MVR (P = 0.008). Postpartum hemorrhage was more common in patients with aortic valve prostheses than in patients with mitral valve prostheses (P = 0.005). The incidence of perinatal death was higher in patients with AVR (P = 0.014). The incidence of live birth was higher in patients with DVR (P = 0.012). The incidence of postpartum hemorrhage was higher in patients who received a daily dose of >5 mg of warfarin than in patients who received ≤5 mg of warfarin (P = 0.05). The incidence of spontaneous abortion was also higher in patients receiving >5 mg of warfarin (P ≤ 0.001), while the incidence of live births was higher in patients receiving ≤5 mg of warfarin (P = 0.008). There was a statistically significant difference between the anticoagulant received during the first trimester and cardiac outcomes. Specifically, patients on heparin developed more heart failure (P = 0.008), arrhythmias (P = 0.008), and endocarditis (P = 0.016). There was a statistically significant relationship between heparin shifts during the first trimester and spontaneous abortion (P = 0.003).CONCLUSIONWarfarin use during the first trimester is safer for the mother but is associated with more fetal loss, especially in doses that exceed 5 mg. The incidence of maternal complications is greater in women who receive LMWH or unfractionated heparin during the first trimester, especially prosthetic valve thrombosis, although the fetal outcome is better because heparin does not cross the placenta.