Analysis of the Relationship Between Hemorheologic Parameters,Aluminum, Manganese,and Selenium in Smokers

Smoking is a significant risk factor in fatal pathologies including cardio-cerebrovascular and respiratory diseases. Aluminum (Al) is a toxic element without known biological function, but with recognized toxic effects. Manganese (Mn) and selenium (Se) are essential trace elements involved in cellular antioxidant defense mechanisms. Al, Mn, and Se carry out their metabolic activities via blood flow and tissue oxygenation. The structure and number of red blood cells (RBC) play important role in tissue oxygenation throughout blood flow. Increased hematocrit (Hct) as a result of probable hypoxia induces disturbed blood flow, RBC aggregation (RBC Agg), RBC deformability index (Tk), and oxygen delivery index (ODI). Therefore, we aimed to investigate the effects of altered Al, Mn, and Se levels on number, structure, and function of RBCs (Hct, blood and plasma viscosity (BV and PV, respectively), RBC Agg, Tk, ODI) in smokers without diagnosis of chronic obstructive pulmonary disease (COPD) in a study group (n = 128) categorized as ex-smokers (ES), smokers (S), and healthy controls (HC). Elements were analyzed in serum using ICP-OES. BV and PV were measured via Brookfield and Harkness viscometers at 37 °C, respectively. Smokers had statistically higher serum Al and Mn levels, BV, RBC, Hgb, Hct, PV, fibrinogen, RBC Agg, Tk₄₅, and pulmonary blood flow rate, but lower serum Se levels and ODI₄₅ values versus HC. In conclusion, increased Al, Mn, and hemorheological parameters and decreased Se and ODI₄₅ might result from inflammatory response in defense mechanism in smokers without diagnosis of COPD. Our results point out that serum Al, Mn, and Se with hemorheological parameters may be beneficial markers of tissue oxygenation and defense mechanism before the clinic onset of COPD in smokers.

     

Mean arterial pressure nonlinearity in an elastic circulatory system subjected to different hematocrits

The level of hematocrit (Hct) is known to affect mean arterial pressure (MAP) by influencing blood viscosity. In the healthy population, an increase in Hct (and corresponding increase in viscosity) tends to raise MAP. However, data from a clinical study of type 2 diabetic patients indicate that this relationship is not universal. Instead, individuals in the lower levels of Hct range display a decrease in MAP for a given rise in Hct. After reaching a minimum, this trend is reversed, so that further increases in Hct lead to increases in MAP. We hypothesize that this anomalous behavior occurs due to changes in the circulatory autoregulation mechanism. To substantiate this hypothesis, we develop a physically based mathematical model that incorporates autoregulation mechanisms. Our model replicates the anomalous U-shaped relationship between MAP and Hct found in diabetic patients in the same range of Hct variability.     

Relationship between synovial fluid and plasma manganese,arginase, and nitric oxide in patients with rheumatoid arthritis

Nitric oxide (NO) participates in the pathogenesis of inflammatory reactions in many autoimmune diseases such as rheumatoid arthritis (RA). There is a reciprocal pathway between arginase and nitric oxide synthese (NOS) for NO production, and Mn is required for arginase activity and stability. To investigate whether NO production related with the arginine-nitric oxide pathway in patients with RA, we measured synovial fluid and plasma nitrite (NO_x) levels, arginase activities, and its cofactor manganese (Mn) concentrations in 21 RA patients and 13 healthy control subjects. Plasma albumin levels were measured as an index of nutritional status. NO_x levels were determined after the reduction of nitrates to nitrites using the Griess reaction. Whereas, synovial fluid arginase activities and Mn levels were found to be significantly lower (p<0.001, p<0.001, respectively), plasma arginase activities and Mn levels were similar in patients with RA when compared to the control subjects. Plasma and synovial fluid NO levels were similar in patients with RA and in healthy subjects (p>0.05, p>0.05, respectively). There were significantly positive correlations between synovial fluid and plasma arginase activities vs Mn content (r=0.543, p=0.011; r=0.516, p=0.017, respectively) and significantly negative correlations between synovial fluid and plasma NO levels vs arginase activities (r=−0.497, p=0.022; r=−0.508, p=0.019 respectively) in the patients group. Our results indicate that the lower concentration of synovial fluid Mn could cause lower arginase activity and this could also upregulate NO production by increasing L-arginine content in patients with RA.     

Influence of magnetostimulation therapy on rheological properties of blood in neurological patients

ABSTRACT

The aim of the study is to test the influence of in vivo magnetostimulation on the rheological properties of blood in neurological patients. Blood circulation in the body depends both on the mechanical properties of the circulatory system and on the physical and physicochemical properties of blood. The main factors influencing the rheological properties of blood are as follows: hematocrit, plasma viscosity, whole-blood viscosity, red cells aggregability, deformability, and the ability of red cells to orient in the flow. The blood samples were collected from neurological patients with pain. Blood samples were collected twice from each patient, that is, before the magnetostimulation and immediately after the therapy. For each blood sample, the hematocrit value was measured using the standard method. Plasma viscosity and whole-blood viscosity were measured by means of a rotary-oscillating rheometer Contraves LS40. Magnetic field was generated by the instrument Viofor JPS® and the magnetostimulation treatments were performed using M1P2 and M1P3 programs. The analysis of the results included estimation of the hematocrit value (Hct), plasma viscosity (η_p), whole-blood viscosity and rheological parameters of Quemada’s model: k₀, k_∞, γ′_c. Plasma viscosity values were obtained from the shear rate dependence of shear stress using the linear regression method. The results obtained in the study suggest that the blood rheological properties change in accord with applied magnetostimulation program.     

F-cell shift and protein loss strongly affect validity of PV reductions indicated by Hb/Hct and plasma proteins

Numerousstudies have focused on alterations in plasma volume (PV) oninterventions like quiet standing, exercise, or heat stress. However,no method seems capable of truly estimating the PV alteration.Therefore, an attempt was made to validate commonly used indexes of PVchanges. Quiet standing was used to cause graded PV reductionsestimated from hemoglobin and hematocrit (Hb/Hct) and from serumconcentrations of total protein, albumin, and "large proteins"(LP; total protein minus albumin). Results indicated the following.1) Hb/Hct, with the merit that themarker (erythrocyte) stays within the circulation, reflect accurately asmall-to-moderate PV loss (10% of control PV). At large PV decrease(15-20% of control), however, F-cell shift can cause Hb/Hct tounderestimate the response by up to 25-30%.2) Albumin and total proteinunderrate PV loss due to protein escape (mainly albumin) from thecirculation. 3) LP alsounderestimate the PV decline due to protein escape but can oftenpredict large PV reductions clearly better than Hb/Hct.4) Prolonged standing can lead topronounced 25% PV decline.

     

Nitric oxide concentrations in gas emanating from the tails of obese rats

Abstract

This study was undertaken to investigate the effects of oral L-arginine administration and exercising training on the NO concentration emanating from rat tail and NO_x in plasma. Obese (fa/fa) Zucker rats (n = 22) were divided into four groups: (1) oral L-arginine administration (A) (n = 6), (2) exercise training (E), (3) exercise training + L-arginine administration (E + A) (n = 5), and (4) non-exercise training + non-L-arginine administration (N) (n = 6). The control (+/+) Zucker rats (n = 22) were also divided into the same four groups. The body weight of the E + A and the A groups was significantly lower than that of the N group. The NO concentration emitted from the tail was higher in the L-arginine (E + A and A) groups than in the non-L-arginine (E and N) groups in both obese and control rats. Exercise training did not affect the skin gas NO concentration in either obese or control rats. Plasma NO_x concentrations in four obese rats were significantly higher than those observed in control rats. Exercise training did not influence the level of plasma NO_x in obese or control rats. In conclusion, this study confirmed that L-arginine administration increases the skin gas NO concentration and obesity increases the plasma NO_x level. The plasma NO_x concentrations were not affected by L-arginine administration or exercise training in obese or control rats.     

Nitric Oxide Correlation with Malondialdehyde and Angiotensin-Converting Enzyme in Healthy Subjects and Patients with Thoracic Wounds

The correlations between nitric oxide products (NO _x ) and the angiotensin-converting enzyme (ACE) activity and malondialdehyde (MDA) were studied in the blood serum of patients with thoracic wounds (the test group) 1, 3, 7, and 14 days after the injury. The severity of a patient's state scored from 8 to 15 on the APACHE II scale. The control group comprised 20 blood donors. One day after wounding, NO _x , MDA, and ACE activity significantly increased. Subsequently, NO _x and ACE activity decreased, whereas MDA increased. A significant negative correlation was found between NO _x and MDA, and a significant positive correlation, between NO _x and ACE activity. The correlations observed in the control group were undetectable in the patients one day after wounding but were restored on the third day. Thus, thoracic injury was accompanied by an increase in NO _x and MDA, which determine the severity of oxidative stress. The positive correlation between NO _x and ACE activity in the control and test groups reflects their concerted action in regulating the physiological functions and metabolism.     

Decreased Serum Hepcidin and Improved Functional Iron Status 6 Months After Restrictive Bariatric Surgery

Excess adiposity is associated with low‐grade inflammation and decreased iron status. Iron depletion in obesity is thought to be mediated by an inflammation‐induced increase in the body's main regulator of iron homeostasis, hepcidin. Elevated hepcidin can result in iron depletion as it prevents the release of dietary iron absorbed into the enterocytes, limiting replenishment of body iron losses. Weight reduction is associated with decreased inflammation; however, the impact of reduced inflammation on iron status and systemic hepcidin in obese individuals remains unknown. We determined prospectively the impact of weight loss on iron status parameters, serum hepcidin, inflammation, and dietary iron in 20 obese premenopausal females 6 months after restrictive bariatric surgery. At baseline, the presence of iron depletion was high with 45% of the women having serum transferrin receptor (sTfR) >28.1 nmol/l. Differences between baseline and 6 months after surgery for BMI (47.56 vs. 39.55 kg/m²; P < 0.0001), C‐reactive protein (CRP) (10.83 vs. 5.71 mg/l; P < 0.0001), sTfR (29.97 vs. 23.08 nmol/l; P = 0.001), and serum hepcidin (111.25 vs. 31.35 ng/ml; P < 0.0001) were significantly lower, whereas hemoglobin (Hb) (12.10 vs. 13.30 g/dl; P < 0.0001) and hematocrit (Hct) (36.58 vs. 38.78%; P = 0.001) were significantly higher. Ferritin and transferrin saturation (Tsat) showed minimal improvement at follow‐up. At baseline, hepcidin was not correlated with sTfR (r = 0.02); however, at follow‐up, significant correlations were found (r = ?0.58). Change in interleukin‐6 (IL‐6) from baseline was marginally associated with decreased log serum hepcidin (Δ IL‐6: β = ?0.22; P = 0.15), whereas change in BMI or weight was not. No significant difference in dietary iron was noted after surgery. Weight loss in obese premenopausal women is associated with reduced serum hepcidin and inflammation. Reduction in inflammation and hepcidin likely allow for enhanced dietary iron absorption resulting in an improved functional iron profile.     

Alterations in blood volume following short-term supramaximal exercise

To investigate the role of high-intensity intermittent exercise on adaptations in blood volume and selected hematological measures, four male subjects aged 19-23 yr [peak O2 consumption (VO2max) = 53 ml X min-1 X kg-1] performed supramaximal (120% VO2max) cycle exercise on 3 consecutive days. Each exercise session consisted of intermittent work performed as bouts of 1-min work to 4-min rest until fatigue or until a maximum of 24 repetitions had been completed. Measurements on blood samples were made before the exercise period and 24 h after the last exercise session. Plasma volume (PV) estimated using 131I-human serum albumin increased by 11.6% (3,504 vs. 3,912 ml; P less than 0.05). Total blood volume (TBV) based on PV and hematocrit (Hct) values increased by 4.5% (5,798 vs. 6,059 ml; P less than 0.05), whereas red cell volume (RCV) decreased by 6.4% (2,294 vs. 2,147 ml; P less than 0.05). Measurements of hematological indices indicated significant reductions (P less than 0.05) in whole-blood Hct (39.7 vs. 35.5%), hemoglobin concentration (15.5 vs. 13.9 g/100 ml), hemoglobin content (897 vs. 839 g), and red blood cell count (5.15 vs. 4.55 X 10(6) X mm-3). The findings of this study suggest that exercise intensity is a major factor in promoting exercise-induced hypervolemia and that rapid elevations in PV can be induced early in training.     

Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine and 5-(hydroxymethyl) uracil in Smokers

Cigarette smoke is known to generate free radicals by various mechanisms. In this study involving 30 non-smokers and 30 smokers, we show that urinary excretion of 5-(hydroxymethyl) uracil (HMUra) was not different in the two groups (6.54±2.07 vs. 6.70±1.68 nmol/mmol creatinine). In contrast, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGuo) excretion increased by 16% (1.16±0.35 vs. 1.35±0.50 nmol/mmol creatinine, p=0.039). Results concerning 8-oxo-dGuo are in agreement with those of previous studies. We observed significant multiple correlations between HMUra and creatinine (r_p=0.44), BMI (r_p=-0.27) and nicotine derivatives (r_p=0.26). Multiple correlation analysis showed relations between 8-oxo-dGuo on the one hand, and: creatinine (r_p=0.36), nicotine derivatives (r_p=0.29), BMI (r_p=-0.24) on the other.     

Carbon and nitrogen dynamics across a natural precipitation gradient in Patagonia,Argentina

Abstract. Both ecosystem carbon gain and nutrient availability are largely constrained by the magnitude and seasonality of precipitation in arid and semi‐arid ecosystems. We investigated the role of precipitation on ecosystem processes along an International Geosphere Biosphere Programme (IGBP) transect in temperate South America. The transect consists of a contiguous precipitation gradient in the southern region of Argentinean Patagonia (44–45° S), from 100 mm to 800 mm mean annual precipitation (MAP) and vegetation ranging from desert scrub to closed canopy forest. Gravimetric soil water content tracked changes in seasonal and annual precipitation, with a linear increase in soil water content with increasing MAP. Above‐ground net primary production (ANPP) increased linearly along the gradient of precipitation (ANPP =– 31.2 + 0.52 MAP, r²= 0.84, p= 0.028), supporting the relationship that carbon assimilation is largely controlled by available water in these sites, and was in general agreement with regional models of ANPP and rainfall. However, inorganic soil nitrogen was also highly linearly correlated with both MAP ([N] = 0.19 MAP – 32, r²= 0.96, p= 0.003) and ANPP (ANPP = 2.6 [N_inorganic]+59.4, r²= 0.79, p= 0.042), suggesting a direct control of precipitation on nitrogen turnover and an interaction with nitrogen availability in controlling carbon gain. The asynchrony of precipitation and changes in dominant vegetation may play important roles in determining the carbon‐nitrogen interactions along this rainfall gradient.     

Targeted activation of transcription in vivo through hairpin-triplex forming oligonucleotide in Saccharomyces cerevisiae

The aims of the present study were to analyse the effects of an oral daily dose (10 mg/kg) of the dietary flavonoid quercetin for five weeks in two-kidney, one-clip (2K1C) Goldblatt (GB) hypertensive rats. The evolution of systolic blood pressure was followed by weekly measurements, and morphological variables, proteinuria, plasma nitrates plus nitrites (NO_x) and thiobarbituric acid reactive substances (TBARS), liver oxidative stress markers and endothelial function were determined at the end of the experimental period. Quercetin treatment reduced systolic blood pressure of GB rats, producing no effect in control animals. It also reduced cardiac hypertrophy and proteinuria developed in GB hypertensive rats. Decreased endothelium-dependent relaxation to acetylcholine of aortic rings from GB rats was improved by chronic quercetin treatment, as well as increased endothelium-dependent vasoconstrictor response to acetylcholine and overproduction of TXB₂ by aortic vessels of GB rats, being without effect in normotensive animals. Increased plasma NO_x and TBARS, and decreased liver total glutathione (GSH) levels and glutathione peroxidase (GPX) activity were observed in GB hypertensive rats compared to the control animals. Normalisation of plasma NO_x and TBARS concentrations and improvement of the antioxidant defences system in liver accompanied the antihypertensive effect of quercetin. We conclude that chronic oral treatment with quercetin shows both antihypertensive and antioxidant effects in this model of renovascular hypertension. (Mol Cell Biochem 270: 147–155, 2005)M.F. García-Saura and M. Galisteo are equal contributors to this work     

Optimal Fixing of the Bandwidth-Parameter for the Empirical Regression1,2

The estimator ?₀(x) of the regression r(x) = E (Y | × = x) from measured points (x_i, y_i), i = 1(1) n, of a continuous two-dimensional random variable (X, Y) with unknown continuous density function f(x, y) and with moments up to the second order can be made with the help of a density estimation f?₀(x, y) (see e.g. SCHMERLING and PEIL, 1980). Here f?₀(x, y) still contains free parameters (so-called band-width-parameters), the values of which have to be optimally fixed in the concrete case. This fixing can be done by using a modification of the maximum-likelihood principle including jackknife techniques. The parameter values can be also found from the estimators for r(x). Here the cross-validation principle can be applied. Some numerical aspects of these possibilities for optimally fixing the bandwidth-parameter are discussed by means of examples. If ?₀(x) is used as a smoothing operator for time series the optimal choice of the parameter values is dependent on the purpose of application of the smoothed time series. The fixing will then be done by considering the so-called filter-characteristic of ?C₀(x).     

Nitrite to nitrate molar ratio is inversely proportional to oxidative cell damages and granulocytic apoptosis at the wound site following cutaneous injury in rats

Nitric oxide (NO) metabolism in response to the inflammatory cell infiltration and their apoptosis at the wound site, using a model of subcutaneously implanted sponges in Albino Oxford rats, were examined. The injured animals were sacrificed at days 1, 2 and 3 after the injury. Nitrites, nitrates (final products of NO metabolism), malondialdehyde (an indicator of oxidative cell damages), urea (product of arginase activity) and other parameters were measured both in plasma and wound fluid samples. Nitrite to nitrate molar ratio and sum of nitrites and nitrates (NO_x) were calculated. The total cell numbers were at similar level throughout the examined period, but a gradual decrease of viable granulocytes, mainly due to the increased apoptosis, and the increase of monocyte-macrophage number occurred after the second day. A gradual increase of wound fluid nitrates, NO_x and malondialdehyde suggested the increases of both NO and free oxygen radicals production. Interestingly, wound fluid nitrites peaked at the first day decreasing to the corresponding plasma levels thereafter. Wound fluid nitrite to nitrate molar ratio gradually decreased and negatively correlated both with the number of apoptotic cells (r = −0.752, p < 0.05) and malondialdehyde (r = −0.694, p < 0.05) levels. In conclusion, the inversely proportional relation between nitrite to nitrate molar ratio and both malondialdehyde and apoptotic cell number indicated a mutual relationship between NO metabolism, oxidative cell damages and cell apoptosis at the wound site early after the cutaneous wound. Moreover, the obtained findings suggest that measurement of both nitrites and nitrates contribute to better insight into overall wound NO metabolism.     

Deduction of pulmonary microvascular hematocrit from indicator dilution curves

We have developed a new model describing the relationship between plasma and red cell tracers flowing through the lung. The model is the result of an analysis of the transport of radiolabeled plasma albumin between two flowing phases and shows that differences between red cell and plasma tracer curves are related to microvascular hematocrit. The model was tested in an isolated, blood-perfused dog lung preparation in which we injected⁵¹Cr-labeled red cells and¹²⁵I-labeled plasma albumin into the pulmonary artery. From the tracer concentration-time curves at the venous outflow, we calculatedh _r, the ratio of microvascular hematocrit to large-vessel hematocrit. In 18 baseline experiments,h _r=0.92±0.01 (mn±sem) at a blood flow rate of 10.7±0.3 ml s⁻¹. We determined the effects of (a) glass bead embolization, (b) alloxan, and (c) lobe ligation onh _r. Embolization attenuated the separation between plasma and red cells (increasedh _r), probably as a consequence of passive vasodilation. Alloxan enhanced separation of plasma and red cells (decreasedh _r), possibly as a result of arteriolar vasoconstriction. Ligation of a fraction of the perfused tissue at constant flow did not cause significant change inh _r in the remaining perfused tissue. The model assumes that large-vessel transit times are uniform and that all dispersion occurs in the microvasculature. A theoretical analysis apportioning dispersion between large and small vessels disclosed that the error associated with these assumptions is likely to be less than 15% of the measuredh _r. We conclude from this study that the microvascular hematocrit model describes experimental plasma and red cell curves. The results imply thath _r can be readily deduced from tagged red cells and plasma and can be accounted for in calculating permeability-surface area in diffusing tracer experiments.     

Nitrite/Nitrate (NO<Subscript><Emphasis Type="Italic">x</Emphasis></Subscript>) and Zinc Concentrations in Influenza-associated Encephalopathy in Children with Different Sequela

NOx (NO₂ and NO₃) in CSF obtained from 22 patients with influenza-associated encephalopathy were higher than those of a control group. Within the different prognosis, there were no significant differences in NO_x levels. By analyzing the serum obtained from patients infected with influenza, including encephalopathy, with others, the serum zinc levels did show marked differences between them. Four out of eleven patients with influenza-associated encephalopathy showed low zinc levels below the normal range. However, there were no significant differences in the zinc levels between the group with sequela and without sequela. These results indicate that the increase of NO_x levels detected in influenza-associated encephalopathy relates to the low zinc levels, and both low molecules might play an important role for the cause of encephalopathy.     

Effects of Moderate Aerobic Exercise Training on Hemorheological and Laboratory Parameters in Ischemic Heart Disease Patients

Background and Design

In this study we set out to determine the effects of long-term physical training on hemorheological, laboratory parameters, exercise tolerability, psychological factors in cardiac patients participating in an ambulatory rehabilitation program.

Methods

Before physical training, patients were examined by echocardiography, tested on treadmill by the Bruce protocol, and blood was drawn for laboratory tests. The enrolled 79 ischemic heart disease patients joined a 24-week cardiac rehabilitation training program. Blood was drawn to measure hematocrit (Hct), plasma and whole blood viscosity (PV, WBV), red blood cell (RBC) aggregation and deformability. Hemorheological, clinical chemistry and psychological measurements were repeated 12 and 24 weeks later, and a treadmill test was performed at the end of the program.

Results

After 12 weeks Hct, PV, WBV and RBC aggregation were significantly decreased, RBC deformability exhibited a significant increase (p<0.05). Laboratory parameters (triglyceride, uric acid, hsCRP and fibrinogen) were significantly decreased (p<0.05). After 24 weeks the significant results were still observed. By the end of the study, IL-6 and TNF-α levels displayed decreasing trends (p<0.06). There was a significant improvement in MET (p<0.001), and the BMI decrease was also significant (p<0.05). The vital exhaustion parameters measured on the fatigue impact scale indicated a significant improvement in two areas of the daily activities (p<0.05).

Conclusions

Regular physical training improved the exercise tolerability of patients with ischemic heart disease. Previous publications have demonstrated that decreases in Hct and PV may reduce cardiovascular risk, while a decrease in RBC aggregation and an increase in deformability improve the capillary flow. Positive changes in laboratory parameters and body weight may indicate better oxidative and inflammatory circumstances and an improved metabolic state. The psychological findings point to an improvement in the quality of life.     

The effect of water exchange on bacterioplankton depletion and inorganic nutrient dynamics in coral reef cavities

We studied the effect of water exchange on the depletion (or accumulation) of bacterioplankton, dissolved organic matter and inorganic nutrients in small open framework cavities (50–70 l) at 15 m depth on the coral reef along Curaçao, Netherlands Antilles. The bacterioplankton removal rate in cavities increased with increasing water exchange rates up to a threshold of 0.0045 s⁻¹, reaching values of 50–100 mg C m⁻² total interior cavity surface area (CSA) per day. Beyond the threshold, bacterioplankton removal dropped. The cryptic community is apparently adapted to the average water exchange in these cavities (0.0041 s⁻¹). Dissolved inorganic nitrogen (DIN), nitrate + nitrite (NO _x ) in particular, accumulated in cavity water and the accumulation decreased with increasing water exchange. Net NO _x effluxes exceeded net DIN effluxes from cavities (average efflux rate of 1.9 mmol NO _x vs. 0.8 mmol DIN m⁻² interior CSA per day). The difference is ascribed to net ammonium losses (NH₄) in cavities at reef concentrations >0.025 μM NH₄, possibly due to enhanced nitrification. Dissolved inorganic phosphate accumulated in cavities, but was not related to water exchange. The cryptic biota in cavities depend on water exchange for optimization of consumption of bacterioplankton and removal of inorganic nitrogen. Coral cavities are an evident sink of bacterioplankton and a source of NO _x and PO ₄ ³⁻ .     

Plasma Free Hemoglobin and Microcirculatory Response to Fresh or Old Blood Transfusions in Sepsis

BackgroundFree hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected.MethodsThis is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (<10 or >15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO₂) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed.ResultsSimilar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098–0.219] mg/mL to 0.238 [0.163–0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003).ConclusionsOld RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01584999","term_id":"NCT01584999"}}NCT01584999     

Reference values for serum nitric oxide metabolites in pediatrics

Serum concentration of nitric oxide metabolites (NO_x) is associated with cardiovascular disease risk factors in pediatrics. The aim of this study was to determine sex- and age-specific reference ranges for serum NO_x concentrations in pediatrics. Serum NO_x levels were measured in 401 subjects (189 boys and 212 girls), aged 4–19 years, using the Griess method. Study subjects selected from participants of Tehran lipid and glucose study, an ongoing cohort study aimed at determining of noncommunicable disease risk factors among Tehranian subjects. The International Federation of Clinical Chemistry guidelines and the robust method were used for determining reference values for sample sizes greater or less than 120 respectively. The 95% reference values for serum NO_x concentrations were 13.6–69.2, 11.4–66.0, and 12.2–69.4 μmol/L in boys, girls, and total population respectively. The upper limit of serum NO_x was 28% lower in otherwise healthy overweight and obese boys while it was 6% higher in overweight and obese girls, for both groups compared to their corresponding normal weight subjects. In conclusion, this study, for the first time, reports reference values for serum NO_x levels in healthy children and adolescents.