Applying the Optimized CO Rebreathing Method for Measuring Blood Volumes and Hemoglobin Mass in Heart Failure Patients

Introduction: Determination of blood volume, red cell volume, and plasma volume contributes to the understanding of the pathophysiology in heart failure, especially concerning anemia and volume load. The optimized carbon monoxide (CO)-rebreathing method (oCORM) is used to determine these parameters and hemoglobin mass (Hbmass) in exercise physiology. The applicability of oCORM to determine the intravascular volumes and Hbmass in heart failure patients is currently undetermined because assumptions concerning CO kinetics with oCORM rely on healthy subjects with a normal ejection fraction. Therefore, the aim of the present study is to determine the applicability and the systematic error of oCORM arising from a reduced EF when oCORM is used for measurement of intravascular volumes and Hbmass in heart failure patients.Methods: oCORM was performed in 21 patients with heart failure and a reduced ejection fraction (EF) of < 30% (EFsev) and 25 controls (CONT). CO kinetics in capillary blood was studied 3–15 min after commencement of CO rebreathing. Differences in CO kinetics between the groups were assessed using a generalized linear model. The systematic error for determination of Hbmass with oCORM arising from differences in CO kinetics was assessed using the Monte Carlo method.Results: The CO kinetics was significantly different between EFsev and CONT. In both groups, exposure to CO led to a COHb increase to 6.0 ± 1.0% 3 min after CO rebreathing. There were no CO related side effects or any clinical symptoms. Monte Carlo simulation quantifies the systematic error for determination of Hbmass arising from an impaired ejection fraction to be −0.88%.Conclusion: Our results indicate an impaired vascular mixing of CO when EF is severely reduced. When Hbmass is determined using the original oCORM protocol in heart failure patients with a reduced EF, the systematic underestimation of about 1% should be considered. However, the error arising from this impaired vascular mixing appears small and clinically negligible. Furthermore, application of oCORM was safe and not related to any side effects resulting from CO exposure. In conclusion, oCORM can be used for assessing intravascular volumes and Hbmass in patients with a reduced EF

Frequency of secondary dyslipidemia in obese children

Ulrike Korsten-Reck1, Katrin Kromeyer-Hauschild2, Katrin Korsten1, Manfred W Baumstark1, Hans-H Dickhuth1, Aloys Berg11Department of Rehabilitative and Preventive Sports Medicine, University Medical Center, University of Freiburg, 79106 Freiburg, Germany; 2Institute of Human Genetics and Anthropology, Friedrich-Schiller-University Jena, 07740 Jena, GermanyObjective: This paper reports the frequency, type, and degree of dyslipidemia in obese children before therapeutic intervention. The relationships between lipid values and weight status, as well as lipid values and physical fitness, of these children were also investigated.Design and methods: The initial examination of the Freiburg Intervention Trial for Obese Children (FITOC) measured the values of triglycerides (TG), total cholesterol (C), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in 546 obese children aged 7–12 (body mass index [BMI] > 97th percentile), and compared these values with those of the age- and sex-specific reference group in the Lipid Research Clinics Population Studies Data Book (LRC). Four groups were selected according to the following scheme: A, Normolipidemia; B, Hyper-LDL-cholesterolemia alone; C, Hypo-HDL-C + hypertriglyceridemia; D, Combined hyperlipidemia = Hyper-LDL-C + hypertriglyceridemia. Body mass index, BMI-SDS (corrected BMI), and physical performance in watt/kg body weight were measured.Results: A total of 45.8% of the overweight children showed an abnormal lipid profile. Ten percent of the children had high LDL-C levels (group B), while 15% had increased LDL-C and increased TG (group D) (higher prevalence in boys). In 18.9% we found increased TG, combined with decreased HDL-C values (group C).Conclusion: Obese children are at risk of dyslipoproteinemia and related diseases. Children with the highest BMI-SDS and lowest physical fitness have the lowest HDL-C values and increased TG, indicating a higher risk for the metabolic syndrome.Keywords: atherosclerotic risk, childhood, dyslipidemia, obesit

Clarifying the Link between the Blood Lactate Concentration and Cardiovascular Risk

The blood lactate value at rest (Lac (rest) ) is linked to cardiovascular outcomes. It is unclear whether this association holds true in younger, healthy subjects, especially as the pathophysiological connection between Lac (rest) and cardiometabolic disease is not well understood. The aim of this study is clarifying the link between Lac (rest) and cardiovascular risk, and to study explanatory factors for the variance of Lac (rest) concerning metabolism and physical activity in a population of healthy patient-athletes. The distribution and intra-individual variability of Lac (rest) was assessed based on 9051 samples. The 10-year cardiovascular risk was then approximated using the Framingham risk score in a group of 1315 samples from patient-athletes. Cross-validated linear regression was used to analyze explanatory variables for Lac (rest) and 10-year cardiovascular risk. Lac (rest) is weakly associated with the Framingham score. This association disappears when adjusting for blood lipids. Lac (rest) is also linked to the predominant type of exercise with endurance athletes featuring a higher Lac (rest.) Lac (rest) does not independently predict the estimated cardiovascular risk but is associated with lipid parameters. Moreover, the intra-individual variability of Lac (rest) is high in a relevant number of subjects, which does not point towards the feasibility to use Lac (rest) as an individual risk factor

Flow cytometric assessment of erythrocyte shape through analysis of FSC histograms: use of kurtosis and implications for longitudinal evaluation.

Sphericity of erythrocytes can be estimated from analysis of FSC signal distribution in flow cytometry. Previously, Pearson's coefficient of dissymmetry (PCD) and spherical index (SphI) were applied to determine erythrocyte sphericity from the FSC histogram. The aim of the present study is to illustrate the application of kurtosis as an indicator of erythrocyte sphericity in flow cytometry in a broad range of FSC distributions. Moreover, the possibility of longitudinal evaluation of erythrocyte sphericity is studied. Change of erythrocyte sphericity of 10 healthy subjects was induced by variation of buffer osmolarity to validate applicability of sphericity measures. Agreement between the sphericity indicators was then studied in samples from 20 healthy donors taken at three time points, which were processed through density gradient centrifugation and incubated with FITC-labelled antibodies to induce a broad variation of erythrocyte form (1086 samples). SphI, PCD and kurtosis of FSC distribution were calculated. Correlation of the respective measures, standard error of measurement (SEM) and r ratio (intra- to interindividual variance) were determined to illustrate agreement between the sphericity indicators. In the first study part, all sphericity indicators illustrated change of erythrocyte shape as induced by osmolarity variation. In the second part, correlation between kurtosis and SphI was -0.97 and correlation between kurtosis and PCD was 0.58 (p<0.05). In isotype control samples, correlation between kurtosis and SphI was -0.98 and correlation between kurtosis and PCD was 0.48 (p<0.05). In these samples, mean kurtosis was -0.80 (SEM 0.03), mean SphI was 2.19 (SEM 0.04) and mean PCD was -0.31 (SEM 0.02). r ratios of all measures of sphericity were <0.6. Our results show that kurtosis is closely correlated with SphI in a broad range of erythrocyte FSC distributions. Moreover, all measures of sphericity feature r ratios <0.6, highlighting that erythrocyte sphericity appears as a feasible parameter for individual longitudinal data monitoring

Crystallization of human low density lipoprotein (LDL), a large lipid-protein complex : collection of X-ray data at very low resolution

Human LDL subfractions LDL-2 (d=1.031-1.034 g/ml) and LDL-5 (d=1.040-1.044 g/ml) were crystallized in different crystal forms using polyethylene glycol as a precipitant. Both fractions were from one donor. Crystals of LDL-5 were yellow, hexagonal, and showed no dichroism. Of LDL-2 two dichroitic crystal forms were obtained. One had a rod-like shape with deep notches at both ends (form A), the other was a more compact form with plain surfaces (form B). To be able to measure low order reflections down to 300 Å a special experimental setup was developed. One single crystal was used to obtain a complete native data set of LDL-2 (form A) with an overall internal R-factor of 4.5% for reflections from 100 to 28 Å. Data were collected under cryogenic conditions using synchrotron radiation. The space group is most probably C2 with unit cell dimensions of a=183 Å, b=421 Å, c=385 Å, α=γ=90°, β≈90°. Further optimization of the crystallization conditions and the search for heavy metal derivatives are in progress

Crystallization and Preliminary X-Ray Diffraction Data of Two Different Human Low-Density Lipoprotein (LDL) Subfractions

Human LDL subfractions LDL-2 (d = 1.031 1.034 g/ml) and LDL-5 (d = 1.040 1.044 g/ml) were crystallized in two different crystal forms by using polyethylene glycol as a precipitant. Both fractions were from one donor. Crystals of LDL-5 were yellow, hexagonal, and showed no dichroism. Crystals of LDL-2 were of the same color, had a rodlike shape with notches at both ends, and were highly dichroitic. LDL-2 crystals diffracted to a resolution of 29 Å by using synchrotron radiation. Indexing in P1 resulted in preliminary parameters for the reduced cell of a = 171 Å, b = 438 Å, c = 519 Å, α = 102°, β = 99°, γ = 91. These dimensions are consistent with the size of LDL particles. Using Fourier transform infrared spectroscopy (FTIR) and agarose gel electrophoresis, we could further confirm that the crystals consist of LDL. The FTIR spectrum showed bands characteristic for lipids and protein. Dissolved crystals exhibited a mobility similar to native LDL in agarose gels and could be stained with anti-human apolipoprotein B (apoB)

Signaling ammonium across membranes through an ammonium sensor histidine kinase

Contains fulltext : 187717.pdf (publisher's version ) (Open Access)11 p

Descriptive statistics for measures of sphericity.

<p>Mean values, SEM, intra- and inter-individual standard deviation (SD) and r ratio in IgG2b isotype control samples (representative for all IgG isotype controls) of CONT.</p