Abnormal Rheology Research Articles

Patient-specific blood rheology in sickle-cell anaemia.

Sickle-cell anaemia (SCA) is an inherited blood disorder exhibiting heterogeneous cell morphology and abnormal rheology, especially under hypoxic conditions. By using a multiscale red blood cell (RBC) model with parameters derived from patient-specific data, we present a mesoscopic computational study of the haemodynamic and rheological characteristics of blood from SCA patients with hydroxyurea (HU) treatment (on-HU) and those without HU treatment (off-HU). We determine the shear viscosity of blood in health as well as in different states of disease. Our results suggest that treatment with HU improves or worsens the rheological characteristics of blood in SCA depending on the degree of hypoxia. However, on-HU groups always have higher levels of haematocrit-to-viscosity ratio (HVR) than off-HU groups, indicating that HU can indeed improve the oxygen transport potential of blood. Our patient-specific computational simulations suggest that the HVR level, rather than the shear viscosity of sickle RBC suspensions, may be a more reliable indicator in assessing the response to HU treatment.

Abnormal Regulation of Microvascular Tone inaMurine Model of Sickle Cell Disease Assessed byContrast Ultrasound.

Microvascular dysregulation, abnormal rheology, and vaso-occlusive events play a role in the pathophysiology of sickle cell disease (SCD). The aim of this study was to test the hypothesis that abnormalities in skeletal muscle perfusion in a murine model of SCD could be parametrically assessed by quantitative contrast-enhanced ultrasound perfusion imaging. A murine model of moderate SCD without anemia produced by homozygous β-globin deletion replaced by human βs-globin transgene (NY1DD-/-; n=18), heterozygous transgene replacement (NY1DD+/-; n=19), and C57Bl/6 control mice (n=14) was studied. Quantitative contrast-enhanced ultrasound of the proximal hindlimb skeletal muscle was performed at rest and during contractile exercise (2Hz). Time-intensity data were analyzed to measure microvascular blood volume (MBV), microvascular blood transit rate (β), and microvascular blood flow. Erythrocyte deformability was measured by elongation at various rotational shears. At rest, muscle MBV was similar between strains, whereas β was significantly (P=.0015, analysis of variance) reduced to a similar degree in NY1DD-/- and NY1DD+/- compared with wild-type mice (0.24±0.10, 0.16±0.07, and 0.34±0.14 sec(-1), respectively), resulting in a reduction in microvascular blood flow. During contractile exercise, there were no groupwise differences in β (1.43±0.67, 1.09±0.42, and 1.36±0.49 sec(-1) for NY1DD-/-, NY1DD+/-, and wild-type mice, respectively) or in microvascular blood flow or MBV. Erythrocyte deformability at high shear stress (≥5Pa) was mildly reduced in both transgenic groups, although it was not correlated with blood flow or β. Contrast-enhanced ultrasound in skeletal muscle revealed a lower microvascular blood transit rate in the NY1DD model of SCD and sickle trait but no alterations in MBV. The abnormality in microvascular blood transit rate was likely due to vasomotor dysfunction, because it was abrogated by contractile exercise and at rest was only weakly related to erythrocyte deformability.

Noninvasive Detection of Hematocrit and the Mean Corpuscular Hemoglobin Concentration Levels by Vis-NIR Spectroscopy

Hematocrit (HCT) and mean hemoglobin concentration(MCHC) play a very important role in preventing cardiovascular disease and anemia. A method was developed on the basis of spectroscopy to detect HCT and MCHC non-invasively and accurately. The anatomical study showed that the blood rheology abnormalities and blood viscosity's changes can cause the changes of tongue, so there is a certain correlation between tongue and blood components. Reflectance spectrums from the tongue tips of 240 volunteers were collected, then the tongue pictures were captured and the biochemical analysis results were recorded at the same time. The 240 samples were separated into two parts: calibration sample and test sample. Spectra were then subjected to a partial least squares regression (PLSR) analysis to develop mathematics models for predicting HCT levels. The correlation between the data and prediction of HCT and MCHC yielded calibration samples value of 0.998 and 0.938. HCT and MCHC levels of test samples predicted by this model from Visible-Near infrared spectra provided a coefficient of determination in prediction of 0.979 and 0.883 with an average relative error of prediction of 1.65% and 1.88%, a root mean square error of prediction of 4.066 and 4.139. From the experiment results we can see that the model which was built before can better predict the HCT and MCHC, and the results also showed that spectrometry method may provide a promising approach to the noninvasive measurement of human HCT and MCHC with a combination of PLSR analysis.

Analysis of Mechanical Behavior of Red Cell Membrane in Sickle Cell Disease

Sickle cell disease (SCD) is a disease of abnormal rheology. The rheological properties of normal erythrocytes appear to be largely determined by those of the red cell membrane. In SCD, the intracellular polymerization of sickle he- moglobin upon deoxygnation leads to marked increase in intracellular viscosity and elastic stiffness and also having indirect effects on cell membrane .To examine mathematically, the abnormal cell rheology behavior due to polymerization process and that due membrane abnormalities , we mechanically modeled the whole cell deformability as viscoelastic solid and proposed a Voigt-model of nonlinear viscoelastic solid constitutive relation as mixture''of an elastic and viscous dissipative parts, with parameters of elastic and viscous moduli. The elastic part used to express stress-strain relations via strain energy function of the material and the viscous part derivation depends on strain - rate of deformation. The combination of both constitutive expressions is used to predict the viscoelastic properties of normal and sickle erythrocyte. Furthermore, sickle hemoglobin polymerization also leads to alter the osmotic behavior of the cell and to investigate such osmotic effect; we employ the van't Hoff law of osmotic pressure versus volume relation. The analysis of both formulations presented well the abnormal rheological /mechanical characterization of sickle erythrocyte membrane as we understood and concluded from our results.

Ulcerating stasis dermatitis of the forearm due to arteriovenous fistula: A case report and review of the published work

Stasis ulcers of the upper limbs are rare, and only 30 cases have been reported, all of which were due to rheological abnormalities. A 59-year-old woman sustained an injury to her right upper limb, resulting in incomplete transections of the brachial artery and the brachial vein. Emergent reconstruction of the brachial artery was performed. Raynaud's phenomenon was observed postoperatively, followed by extreme edema, eczematization and the development of ulcers on the forearm. She was referred to our hospital for treatment. 3-D computed tomography (CT) revealed end-to-end anastomosis of the brachial artery and the brachial vein. An additional brachial-radial artery bypass and closure of the anastomosis dramatically improved her skin symptoms. Vascular anomalies including surgery should be suspected when patients present with stasis dermatitis of the upper limbs.

The Role of Renin-Angiotensin System in Prothrombotic State in Essential Hypertension

Rheological, haemostatic, endothelial and platelet abnormalities appear to play a role in the thrombotic complications of hypertension. This prothrombotic/hypercoagulable state in hypertension may contribute to the increased risk and severity of target organ damage. It can be induced by the activated renin-angiotensin system (RAS), with abnormalities in endothelial and platelet function, coagulation and fibrinolysis. Treatment of uncomplicated essential hypertension by RAS targeting antihypertensive therapy could result in a reversal of prothrombotic abnormalities, contributing to a reduction of thrombosis-related complications. Since angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have two distinct mechanisms of RAS interruption, it is hypothesized that each therapy might have different impact on the prothrombotic state in hypertensive patients. Some studies demonstrate a beneficial effect of both ACE inhibitors and ARBs on prothrombotic state, in addition to their efficacy to normalize elevated blood pressure. The potentially antithrombotic effect of the RAS inhibiting agents may in turn support the preservation of cardiovascular function. Available data may offer an additional explanation for the efficacy of the RAS targeting agents in the prevention of cardiovascular events in patients with atherosclerotic vascular disease.

Effects of different resuscitation fluids on the rheologic behavior of red blood cells, blood viscosity and plasma viscosity in experimental hemorrhagic shock

Background Hemorrhagic shock is associated with severe rheological abnormalities. We hypothesized that in the setting of hemorrhagic shock, resuscitation can alter hemorheological characteristics dramatically, and different fluids cause different effects. The aim of this study was to investigate whether the type of fluid administered has an impact on hemorheological characteristics at the early stage of resuscitation in a rodent model of hemorrhagic shock. Methods Animals were randomized into five groups: (1) sham hemorrhage (SHAM); (2) shock and sham resuscitation (SHOCK); (3) shock and resuscitation with normal saline 32 ml/kg (NS); (4) shock and resuscitation with 7.5% hypertonic saline 4 ml/kg (HS); (5) shock and resuscitation with 7.5% hypertonic saline/6% Dextran 70 4 ml/kg (HSD). Hemorheological characteristics were measured at 60 min after resuscitation. Results Results showed that NS resuscitation deteriorated red blood cell (RBC) deformability compared with the SHOCK group. The HS group showed improved RBC deformability compared with the NS group, although the differences were not statistically significant. There were significant improvements of RBC deformability at all shear rates in the HSD group compared with the NS group. Whole blood and plasma viscosities decreased significantly in the SHOCK group compared with the SHAM group. At shear rates of 60 and 150 s −1, the NS group decreased whole blood viscosity compared with the SHOCK group. The HSD group showed elevated plasma viscosity compared with the SHOCK, NS and HS groups. Conclusion These results suggested that at the early stage of hemorrhagic shock resuscitation, hypertonic–hyperoncotic resuscitation could improve RBC deformability compared with isotonic crystalloid resuscitation. Dextran 70 could elevate plasma viscosity to nearly baseline level. These effects of hypertonic–hyperoncotic resuscitation could be beneficial to maintain microcirculation.

Effects of cardiotonic pill on RBC rheologic abnormalities in HFD-induced mice and LPL deficient mice

The lipoprotein lipase deficient (LPL-/-) mice and high fat-diet (HFD) induced hypertriglyceridemic mice were used to investigate the effects of cardiotonic pill (CP) on RBC rheologic abnormalities. Mice were randomly divided into the following five groups: the control group; the untreated HFD group; the untreated LPL-/- group; the treated HFD group; and the treated LPL-/- group, and the treated HFD and LPL-/- mice were administered with CP twice a day (400 mg/kg/day) orally for four weeks. Then, plasma triglyceride (TG), RBC deformation index (DI), orientation index (DI)or and RBC electrophoretic time (EPT) were measured. Compared with the untreated HFD mice, TG level and EPT reduced and DI and (DI)or increased markedly in the treated HFD mice (P<0.05). However, compared with the untreated LPL-/- mice, these parameters in the treated LPL-/- mice had no statistically significant changes (P>0.05). Our data show that CP can lower plasma TG level and ameliorate RBC rheologic abnormalities in the HFD-induced hypertriglyceridemic mice, but it losses its capacity in the LPL deficient animals. The results indicate that LPL may be one of the important targets for CP regulating lipometabolism and rheologic abnormalities.

Physiological Responses of Sickle Cell Trait Carriers during Exercise

Growing evidence suggests that physiological responses during exercise in sickle cell trait (SCT) carriers might differ from persons with normal haemoglobin. Epidemiological and experimental results support the view that SCT carriers could be advantaged in certain anaerobic activities, but the underlying physiological and bio-cellular mechanisms remain unknown. Maximal aerobic physical fitness (i.e. maximal oxygen consumption and maximal aerobic power) is not affected by SCT; however, recent studies suggest that SCT carriers could be characterized by a lesser aerobic capacity. Discrepancies are frequently reported in the literature concerning lactate metabolism during exercise in this population. While some studies observed higher blood lactate concentration during exercise in individuals carrying SCT compared with subjects with normal haemoglobin, others described lower concentration, which suggests a paradoxical lower lactate production by exercising muscles and/or greater ability to clear circulating lactate in SCT carriers. One of the most debated topics is the clinically benign condition of SCT, particularly during strenuous exercise. SCT carriers are usually involved in physical exercise without developing medical complications; however, several authors have presented case reports of SCT carriers who have collapsed and died unexpectedly during or after exercise. Blood rheological, haemostatic and vascular adhesion mechanism abnormalities in combination with environmental factors, such as heat strain, might play a role in the occurrence of these fatal scenarios. Several physiological differences have been observed between SCT carriers and non-SCT carriers, which make it necessary to consider the former as a specific population in response to exercise.

Blood rheology abnormalities and vascular cell adhesion mechanisms in sickle cell trait carriers during exercise

Sickle cell trait (SCT) is usually considered a benign disorder compared with sickle cell anemia (SS hemoglobinopathy). However, several authors have reported cases of exercise-related sudden death in this population. Among the mechanisms that could be involved in these fatal complications, vaso-occlusive processes, such as those occurring in SS hemoglobinopathy, may play a role. In sickle cell anemia, these vaso-occlusive processes involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet rolling on the vascular wall. Recent results suggest that adhesion phenomena could be amplified in SCT carriers during exercise compared with non-carriers. Other mechanisms like alterations in blood coagulation and/or hemorheological properties can also favor the occurrence of vaso-occlusive processes. Although few studies have reported coagulation disturbances in SCT carriers at rest, we recently observed no difference between this population and control subjects in response to exercise. In contrast, by studying the behavior of several hemorheological parameters in response to several types of exercise, we detected hemorheological abnormalities in individuals with SCT. These abnormalities included higher red blood cell rigidity and higher blood viscosity in the SCT carriers compared with the non-carriers, particularly during the late recovery period (24 and 48 h after exercise). Therefore, we can suggest that the risks for microvascular complications in SCT carriers in response to exercise could be dependent on alterations in blood rheology and vascular adhesion processes.

Last Word on Point:Counterpoint “Sickle cell trait should/should not be considered asymptomatic and as a benign condition during physical activity”

POINT-COUNTERPOINTLast Word on Point:Counterpoint “Sickle cell trait should/should not be considered asymptomatic and as a benign condition during physical activity”Philippe Connes, Marie-Dominique Hardy-Dessources, and Olivier HuePhilippe Connes, Marie-Dominique Hardy-Dessources, and Olivier HuePublished Online:01 Dec 2007https://doi.org/10.1152/japplphysiol.00855.2007MoreSectionsPDF (30 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat to the editor: We greatly appreciate the contributions made by Bergeron and Baskurt and Meiselman (1) and we sincerely agree with their remarks. Although sickle cell trait (SCT) carriers are characterized by blood rheological abnormalities (3) and sometimes hemostatic and vascular cell adhesion perturbations, most of the SCT carriers performed exercise without any symptoms. As underlined by Baskurt and Meiselman (1), the vascular autoregulatory reserve is undoubtedly a critical point in the fatal events reported in SCT carriers during exercise that requires further investigation. Particularly, the interrelationships between nitric oxide metabolism and blood rheology, such as red blood cell aggregation and deformability, must be investigated in SCT carriers. Kark et al. (2) reported that the relative risk of exercise-related death unexplained by pre-existing disease was 28 for SCT. The excess exercise-related death with SCT was likely to result from the immediate stress of exercise. About 50% of the deaths resulted from heat illness due to over exertion and the remaining cases were idiopathic sudden deaths. It is difficult to prove a causal relationship between SCT conditions and these sudden deaths and it is possible that co-risk factors, such as heat stress, viral illness, poor physical conditioning, and dehydration, have precipitated the occurrence of these fatal complications. Of course, SCT carriers must practice sports, as everyone, but basic recommendations have to be provided by medical staff and trainers, such as wear light clothes, start exercise gradually, and drink adequately during exercise. The last recommendation is particularly important for SCT carriers because it seems that they might be naturally more predisposed to dehydration due to their inability to concentrate their urine when deprived of water (4). This defect might make SCT carriers less able to conserve water than noncarriers.The National Athletic Trainers' Association (NATA) in the United States recently elaborated a task force that includes more than 20 organizations. They strongly propose that colleges and high schools show greater awareness of the typically benign condition, which poses a grave risk during intense exertion of physical activity. The Task Force consensus recommends confirming SCT status in all athletes' preparticipation physical examinations and provides details on measures that can reduce the risk of collapse during sports and exercise related to SCT among athletes.FOOTNOTESThe costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.REFERENCES1 Baskurt OK, Meiselman HJ, Bergeron MF. Comments on Point:Counterpoint “Sickle cell trait should/should not be considered asymptomatic and as a benign condition during physical activity.” J Appl Physiol; doi:10.1152/japplphysiol.00886.2007.Google Scholar2 Kark JA, Posey DM, Schumacher HR, Ruehle CJ. Sickle-cell trait as a risk factor for sudden death in physical training. N Engl J Med 317: 781–787, 1987.Crossref | PubMed | ISI | Google Scholar3 Monchanin G, Connes P, Wouassi D, Francina A, Djoda B, Banga PE, Owona FX, Thiriet P, Massarelli R, Martin C. Hemorheology, sickle cell trait, and alpha-thalassemia in athletes: effects of exercise. Med Sci Sports Exerc 37: 1086–1092, 2005.Crossref | PubMed | ISI | Google Scholar4 Sherry P. Sickle cell trait and rhabdomyolysis: case report and review of the literature. Mil Med 155: 59–61, 1990.Crossref | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: P. Connes, Laboratoire ACTES (EA 3596), Département de Physiologie, Université des Antilles et de la Guyane, Guadeloupe (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited BySICKLE CELL DISEASESickle Cell Trait More from this issue > Volume 103Issue 6December 2007Pages 2144-2144 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00855.2007History Published online 1 December 2007 Published in print 1 December 2007 Metrics

Assessment of erythrocyte shape by flow cytometry techniques

Background: Red blood cell (RBC) rheology is altered in different diseases, including acute conditions such as patients in intensive care units (ICU) with sepsis or with an inflammatory reaction due...

Venodynamic and Hemorheological Variables in Patients with Diabetes Mellitus

The association between diabetes mellitus and the occurrence of peripheral vascular disease has been well established. However, it is unclear whether the venous circulation is also affected. This study was done to determine whether there is impairment of venous function in the legs of patients with diabetes mellitus and the relationship with rheological parameters. Venous occlusion plethysmography was used to assess venous circulation in the legs of 54 diabetic patients at the University Hospital of the West Indies. The venodynamic variables measured were segmental venous capacitance (SVC), maximum venous outflow (MVO), and venous emptying time (VET) at the calf, ankle and great-toe. Plasma fibrinogen concentration (PFC), relative plasma viscosity (RPV) and whole blood viscosity (WBV) were measured by standard techniques. Calf SVC was significantly less in neuropathic diabetic patients (ND) than in non-diabetic subjects (C) (p <0.05). MVO at the calf of ND and non-neuropathic diabetic patients (NND) was significantly lower than in C (p <0.05). VET at the ankle and calf were significantly shorter in ND compared with NND (p <0.05). No statistically significant differences in SVC, MVO and VET among the three groups were observed at the great-toe. PFC was significantly higher in diabetic patients than in the control group. No significant differences were detected in WBV at high or low shear rates. These findings strongly suggest impairment of venous function in the legs of diabetic patients. This impairment of venous function appears to be unrelated to rheological abnormalities.

C-reactive protein and red cell aggregation correlate with late venous function after acute deep venous thrombosis

Risk factors leading to development and subsequent progression of chronic venous insufficiency after acute deep venous thrombosis (DVT) are only partially identified. Inflammation and rheologic abnormalities might have a causative role. The purpose of this study was to investigate C-reactive protein (CRP), D -dimer, and blood rheologic parameters in patients after acute DVT in relation to clinical outcome. Patients with a history of acute proved DVT underwent clinical examination and duplex ultrasound scanning of the veins, and Venous Clinical Severity Score (VCSS) and Venous Segmental Disease Score (VSDS) were calculated. Further, CRP, D -dimer, and several rheologic parameters were determined and related to outcome as assessed with venous scores. Forty-three patients were examined 28 (median) months after the index event. Patients had higher CRP ( P < .001), D -dimer ( P < .001), red blood cell aggregation ( P < .01), fibrinogen concentration ( P < .01), and leukocyte count ( P < .05) than did healthy control subjects. CRP and red blood cell aggregation were positively correlated with VCSS ( r = 0.42 and P < .01, and r = 0.30 and P < 0.05, respectively). Multivariate regression analysis showed that the relation between CRP and VCSS was independent of other laboratory and rheologic parameters and of age, total thrombus load, duration of compression therapy after the index event, recurrence, recanalization, and presence of comorbid conditions ( P < .05). CRP is independently related to the severity of venous dysfunction in patients after acute DVT. Chronic inflammation as well as changes in blood rheologic parameters may be causally involved in the development of chronic venous insufficiency occurring in the medium-term and long-term course after acute DVT.

In Vivo Studies of Sickle Red Blood Cells

The defining clinical feature of sickle cell anemia is periodic occurrence of painful vasoocclusive crisis. Factors that promote trapping and sickling of red cells in the microcirculation are likely to trigger vasoocclusion. The marked red cell heterogeneity in sickle blood and abnormal adhesion of sickle red cells to vascular endothelium would be major disruptive influences. Using ex vivo and in vivo models, the authors show how to dissect the relative contribution of heterogeneous sickle red cell classes to adhesive and obstructive events. These studies revealed that (1) both rheological abnormalities and adhesion of sickle red cells contribute to their abnormal hemodynamic behavior, (2) venules are the sites of sickle cell adhesion, and (3) sickle red cell deformability plays an important role in adhesive and obstructive events. Preferential adhesion of deformable sickle red cells in postcapillary venules followed by selective trapping of dense sickle red cells could result in vasoocclusion. An updated version of this 2-step model is presented. The multifactorial nature of sickle red cell adhesion needs to be considered in designing antiadhesive therapy in vivo.

The impact of peripheral arterial disease on circulating platelets

Introduction: To test the hypothesis that circulating platelets display evidence of reversible interactions with atherosclerotic lesions, platelet α-granule content and propensity for microaggregate formation were measured in samples from normal donors ( n=65) and from patients with either peripheral arterial disease ( n=47) or renovascular hypertension ( n=22). To measure the effect of a defined arterial injury on platelet function, platelet samples were compared before and 30 min after elective angioplasty. Materials and methods: P-selectin was measured after strong stimulation of ultra-dilute platelets with thrombin (10 nM). Microaggregation was measured as a platelet count deficit in citrate-anticoagulated platelet-rich plasma (PRP) relative to that predicted from the count in EDTA-anticoagulated blood. Results: Platelet α-granule P-selectin was significantly lower from platelets of patients compared to normal donors. In addition, platelets from patients have a significantly greater propensity to form microaggregates in citrate anticoagulant. In contrast to atherosclerotic renovascular hypertension, platelets from patients with fibromuscular dysplasia, a distinct non-inflammatory cause of arterial stenosis, do not differ significantly from normal donors. Other than the PRP platelet count, which rose transiently following angioplasty, other platelet measures were unchanged by the injury. Conclusions: Atherosclerotic arterial disease is associated with an increased share of platelets unable to express P-selectin and an increased fraction of platelets that microaggregate in citrate anticoagulant. These platelet alterations are not completely explained by either focal arterial injury or abnormal rheology associated with arterial stenosis but appear to be an effect of the atherosclerotic process.

Prognostic value of interleukin-6, plasma viscosity, fibrinogen, von Willebrand factor, tissue factor and vascular endothelial growth factor levels in congestive heart failure.

Congestive heart failure (CHF) carries a poor prognosis with a high mortality rate, frequent hospitalizations and increased risk of thrombotic complications such as stroke. Cytokines may contribute to the progression and prothrombotic state of CHF, including the pro-inflammatory interleukin-6 (IL-6) and the pro-angiogenic vascular endothelial growth factor (VEGF), both of which are raised in CHF. The procoagulant properties of both cytokines may be mediated via tissue factor (TF), a potent clotting activator. We hypothesized that plasma levels of these markers, as well as levels of plasma viscosity, fibrinogen, soluble P-selectin and von Willebrand factor (markers of abnormal rheology, clotting, platelet activation, and endothelial damage, respectively) will be useful in predicting morbidity and mortality in chronic stable CHF. One hundred and twenty consecutive out-patients with chronic stable CHF (92 males; mean [SD] age 64 [11] years, mean [SD] left ventricular ejection fraction of 29 [6]%) were recruited and followed for 2 years during which 42 patients reached a clinical end-point of all-cause mortality and cardiovascular hospitalizations, including stroke and myocardial infarction. Plasma IL-6 (P=0.003) and TF (P=0.013) levels, but not other research indices, were higher in those who suffered events compared with those without events. Predictors of end-points were high (> or =median) TF (P=0.011), and IL-6 (P=0.023) levels, as well as the lowest quartile of a left ventricular ejection fraction (P=0.007). A strong correlation was present between TF and IL-6 levels (r=0.59; P<0.0001) and with VEGF levels (r=0.43; P<0.0001). IL-6 and TF are predictors of poor prognosis in chronic CHF, raising the hypothesis that IL-6 may contribute to the progression and thrombotic complications of CHF via its actions on TF expression. Although VEGF did not independently predict outcome in chronic CHF, the possibility arises that it may act with IL-6 to induce TF expression.

Alterations of red blood cell shape and sialic acid membrane content in septic patients.

To investigate the relationship between red blood cell (RBC) shape and modifications of RBC membrane protein content in critically ill patients with or without sepsis compared with healthy control volunteers. Prospective, observational in vitro study. University-affiliated cell biology laboratory. Human erythrocytes from healthy volunteers and nonseptic and septic intensive care unit patients. Sialic acid membrane content was measured on isolated RBC membrane proteins by high-performance liquid chromatography. RBC shape, estimated by the spherical index (M2/M1) or by the moment and effect of osmolality on RBC shape, was studied by flow cytometry at 25 degrees C. Glycophorin A content was measured with antiglycophorin antibodies in flow cytometry. Sialic acid content was lower in the septic than in the nonseptic patients (1.98 +/- 0.79, 2.20 +/- 0.39 microg/100 microg membrane protein, respectively; p =.01) and than in the volunteers (2.71 +/- 1.00 microg/100 microg membrane protein; p <.001). No significant difference was found in glycophorin A content between septic and nonseptic patients. RBCs from septic patients had a more spherical shape in isotonic solution than those of healthy volunteers, as assessed by a computed spherical index (M2/M1 ratio: 1.68 +/- 0.34 vs. 1.95 +/- 0.32; p =.001). Only the RBCs of septic patients failed to change their shape in hypo-osmolar solution (M2/M1 ratio: 1.68 +/- 0.34 in iso-osmolar, 1.56 +/- 0.28 in hypo-osmolar solution; p =.17). There was a significant correlation between the RBC shape evaluated by the spherical index or by the moment of the cytometric histogram and the sialic acid membrane content in all critically ill patients (septic and nonseptic patients) (r2 =.16, p =.01 for the moment, and r2 =.17, p =.01 for the spherical index, respectively). RBCs of septic patients are characterized by a more spherical shape, a decreased capacity of sphericity in hypo-osmolar solution, and a reduction in the sialic acid content of the RBC membrane. These modifications in RBC shape and membrane may contribute to the RBC rheologic abnormalities frequently described in sepsis.

Rheological abnormalities and thromboembolic complications in heart disease: spontaneous echo contrast and red cell aggregation.

The role of abnormal rheological changes in the pathogenesis of thromboembolism has received much attention in recent years, especially in the field of cardiology. Such changes are sometimes seen in an echocardiogram as a smokelike haze known as spontaneous echo contrast (SEC). The presence and severity of SEC correlate with dilated cardiac chambers and the incidence of thromboembolic complications. It is caused by increased red cell aggregation and increased fibrinogen levels, both of which are known risk factors for thrombosis. Although not used clinically, measurements of red cell aggregation can be made in research settings. This can provide findings that give insight into factors causing increased red cell aggregation. A small series of patients with angina pectoris was studied with the Myrenne aggregometer for red cell aggregation. The results, which show correlation between the plasma fibrinogen and triglyceride levels, are presented. As yet, there are only a few therapeutic guidelines for the correction of abnormally high fibrinogen levels in patients at risk.

Abnormal rheology in cyanotic congenital heart disease--a factor in non-immune nephropathy.

There are few data on non-immune nephropathy in cyanotic congenital heart disease reported in the literature. Rheologic changes have been suspected to be involved in the pathogenesis. This study was performed to describe the characteristics of renal functional and hemorheological abnormalities in a large group of patients with cyanotic congenital heart disease. Thirty-five cyanotic patients with median oxygen saturation of 82% (range 38-92%), age 18 years (range 5-63 years), and 13 acyanotic controls with atrial septal defect, age 37 years (range 20-66 years) were included. Red cell indices, blood and plasma viscosity were analyzed. Renal function was evaluated with measurements of albumin, alpha1-microglobulin, transferrin, immunoglobuline, and N-acetyl-beta-D-glucosaminidase in the urine. Fifteen cyanotic patients and 1 control patient had pathologic albuminuria (p < 0.05). In cyanotic patients blood and plasma viscosity, erythrocyte count, hemoglobin, and hematocrit were elevated while mean corpuscular volume and mean corpuscular hemoglobin were decreased (p < 0.05). The possible impact of blood hyperviscosity on proteinuria is indicated by multiple regression analysis (odds ratio = 0.5, confidence intervals 22-130, p < 0.05). Our study shows a coincidence of elevated blood viscosity and proteinuria in patients with cyanotic congenital heart disease. This observation supports the hypothesis that impaired peritubular capillary blood flow with increased intraglomerular blood pressure may add to chronic glomerular dysfunction.