Increase In Whole Blood Viscosity Research Articles

Thrombotic Risk and Calculated Whole Blood Viscosity in a Cohort of Patients With New Diagnosis of Multiple Myeloma.

The pathogenesis of venous thromboembolism in multiple myeloma is still poorly understood because multiple factors are involved. In particular, the increase in whole blood viscosity has a key role and, therefore, we performed an evaluation of some hemorheological determinants in multiple myeloma patients, putting them in relation to the thrombotic risk, with the aim to evaluate if an alteration of the hemorheological pattern was associated with a higher thrombotic risk. We performed an observational retrospective cohort study with data collected from January 2017 to September 2022. In a group of 190 patients with newly diagnosed multiple myeloma, we have examined the trend of calculated blood viscosity according to the Merrill formula, and we stratified the patients for the thrombotic risk in accordance with the IMWG/NCCN guidelines and with IMPEDE VTE score. Using the thrombotic risk stratification proposed by IMWG/NCCN any variation in calculated blood viscosity is evident, while, with the IMPEDE VTE score, we observed an increase in calculated blood viscosity in patients with "intermediate + high" risk. The calculated blood viscosity is higher in subjects presenting an "intermediate + high" thrombotic risk according to the IMPEDE VTE score. This association could therefore lay the groundwork for further research with the aim to confirm the role of hemorheological pattern in MM-related thrombotic risk.

Microcirculatory and Rheological Adaptive Mechanisms at High Altitude in European Lowlander Hikers and Nepalese Highlanders.

Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric-hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric-hypoxic conditions should be considered when planning training and physical activity at altitude.

In Vitro Interactions of Amphiphilic Phosphorous Dendrons with Liposomes and Exosomes-Implications for Blood Viscosity Changes.

Drug delivery by dendron-based nanoparticles is widely studied due to their ability to encapsulate or bind different ligands. For medical purposes, it is necessary (even if not sufficient) for these nanostructures to be compatible with blood. We studied the interaction of amphiphilic dendrons with blood samples from healthy volunteers using standard laboratory methods and rheological measurements. We did not observe clinically relevant abnormalities, but we found a concentration-dependent increase in whole blood viscosity, higher in males, presumably due to the formation of aggregates. To characterize the nature of the interactions among blood components and dendrons, we performed experiments on the liposomes and exosomes as models of biological membranes. Based on results obtained using diverse biophysical methods, we conclude that the interactions were of electrostatic nature. Overall, we have confirmed a concentration-dependent effect of dendrons on membrane systems, while the effect of generation was ambiguous. At higher dendron concentrations, the structure of membranes became disturbed, and membranes were prone to forming bigger aggregates, as visualized by SEM. This might have implications for blood flow disturbances when used in vivo. We propose to introduce blood viscosity measurements in early stages of investigation as they can help to optimize drug-like properties of potential drug carriers.

Surgical Splenectomy Alters Red Cell Rheology in Patients with Sickle Cell Disease

Background: Many patients with sickle cell disease (SCD) require a surgical splenectomy for repeat splenic sequestration or hypersplenism, resulting in worsening anemia and/or thrombocytopenia, or abdominal discomfort. Higher rates of thrombosis, pain crises and acute chest syndrome (ACS) have been reported following surgical splenectomy, although the reasons for this are not known. We hypothesize that this clinical worsening post-splenectomy is due to hemorheological changes; studies of the effects of surgical splenectomy on hemorheology in non-SCD animal models found significant reductions in red cell deformability and increase in whole blood viscosity, or blood thickness, following splenectomy. Understanding the impact of surgical splenectomy on blood rheology is especially relevant for patients with SCD, who have many clinical complications as a result of their high whole blood viscosity for their given hemoglobin levels, and low hematocrit-to-viscosity ratio (HVR), a measure of oxygen carrying capacity. Another important measure of SCD rheology is percent dense red blood cells (%DRBC), red cells with a density>1.11 mg/mL; they are typically the result of cellular dehydration, and are less deformable and more likely to sickle. We therefore sought to use our existing longitudinal rheology data, including measures of viscosity and %DRBC, to evaluate the impact of surgical splenectomy on our pediatric patients with SCD.Methods: We identified seven pediatric patients with multiple measurements of whole blood viscosity and %DRBC, collected before and after surgical splenectomy between November 2013 and April 2018 from SCD patients at Texas Children's Hospital on an IRB approved protocol. The cohort included 4 female and 3 male patients, ages 3-12 years old. Whole blood viscosity was measured using a cone and plate viscometer (DV3T Rheometer, AMETEK Brookfield, Middleboro, MA, USA) at 37 degrees Celsius within 4 hours of sample collection in an EDTA vacutainer tube. CBC data including %DRBC was measured on an ADVIA 120 Hematology System (Siemens Medical Solutions USA, Inc., Malvern, PA, USA). Samples collected 1 month before or after an emergency department visit or within 3 months of a packed red blood cell transfusion were omitted from analysis.Results: We found a significant rise in %DRBC following splenectomy (p=0.01). There was a significant increase in whole blood viscosity at 45 s-1 and 225 s-1 (p=0.006 and p=0.004, respectively) and a decline in hematocrit-to-viscosity ratio (HVR) at 45 s-1 and 225 s-1 (p=0.03 and p=0.03, respectively) (Table 1). Hemoglobin and hematocrit did not significantly change after splenectomy (p=0.6 and p=0.5, respectively), suggesting that the rise in viscosity was due to intrinsic changes in red cell rheology. Platelets increased markedly (p<0.00002), a side effect commonly seen following splenectomy, known to contribute to thrombophilia.Conclusion: Overall, the changes in %DRBC, viscosity, and HVR show a worsening of blood rheology following surgical splenectomy with no evidence of a return to baseline 800 days after splenectomy. The increase in viscosity and reduction in HVR in the setting of a rise in %DRBC suggests that the spleen may have played a role in removing these dense or irreversibly sickled cells. Further studies with a larger cohort and long term observation are needed to further elucidate the relationship between worsening rheology and SCD-related complications reported in the literature post-splenectomy. These rheological changes should be considered as part of the decision making for elective splenectomy, monitored post-splenectomy, and addressed therapeutically where possible. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hemorheological parameters in Monoclonal Gammopathy of Undetermined Significance (MGUS).

There is scarcity of information about the hemorheological pattern in subjects with Monoclonal Gammopathy of Undetermined Significance (MGUS). This preliminary research is focused on the behaviour of whole-blood and plasma viscosity, haematocrit and erythrocyte deformability in the above clinical condition. We enrolled 21 MGUS subjects (10 women and 11 men; mean age 66.4 ± 11.6 years). In fasting venous blood we examined whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit × 100, the ratio between plasma viscosity at low and high shear rate, and the erythrocyte deformability expressed as elongation index. By comparing normal controls to MGUS subjects a significant increase in whole-blood viscosity at high shear rate and in plasma viscosity at low shear rate were observed. In MGUS subjects the ratios between the high and low shear rate blood viscosity and haematocrit × 100, as well as the ratio between the low and high shear rate plasma viscosity were significantly higher. In MGUS subjects a marked decrease in erythrocyte deformability was also observed. The alteration of the hemorheological profile found in these subjects might be involved in the pathogenesis of thromboembolic events, which occur with a high frequency in MGUS.

Characterization and pathophysiological changes of cerebral infarction rat model with qi-deficiency and blood-stasis Syndrome

This study aimed to observe the general state and changes in pathophysiological indexes of multiple cerebral infarction rat model with Qi-deficienty and Blood-stasis syndrome. Rats were randomly divided into 4 groups(with 30 in each group): the normal group, the sham group, the model group and the Yiqi Huoxue recipe group. Rats in the model group and Yiqi Huoxue group were provided with interruptable sleep deprivation for 7 days before the multiple cerebral infarction operation, and followed by another 4 weeks of sleep deprivation; rats in the Yiqi Huoxue group were intragastrically administrated with drug at a dose of 26 g·kg⁻¹, once a day for 4 weeks. The general state was observed, and the pathophysiological indexes were measured at 48 h, 2 weeks and 4 weeks after administration. The results showed that rats in the normal group and the sham group represented a good general state and behaviors, with a normal morphological structure of brain tissues; rats in the model group featured yellow fur, depression, accidie, loose stools and movement disorder, with obvious brain histomorphological damage, which became aggravated with the increase of modeling time; rats in the Yiqi Huoxue group showed release in the general state and above indexes. Compared with the sham group at three time points, rats in the model group showed decrease in body weight, exhaustive swimming time and RGB value of tongue surface image, and increase in whole blood viscosity of the shear rate under 5, 60 and 150 S⁻¹, reduction in cerebral cortex Na⁺-K⁺-ATPase, Ca²⁺-ATPase activity and contents of 5-HT, rise in TXB2 levels and decline in 6-keto-PGF1a in serum(P<0.05, P<0.01). Compared with the model group, rats in the Yiqi Huoxue group showed alleviations in the above indexes at 2 w and 4 w(P<0.05, P<0.01). The results showed that the characterization and pathophysiological indexes in the multiple cerebral infarction rat model with Qi-deficiency and blood-stasis syndrome were deteriorated; Yiqi Huoxue recipe could significantly alliviate the abnormal conditions, which suggested of the model was stable and reliable and the pathophysiologic evolutionary mechanism might be related to energy metabolism dysfunction, vasoactive substance abnormality and changes in neurotransmitters.

Rheological properties of human blood in the network of non-equilibrium thermodynamic with internal variables by means of ultrasound wave perturbation

Abstract This study is focused on the responses of whole blood and erythrocytes in saline solution when subjected to elastic stresses induced by ultrasound wave. Using a theoretical approach we obtained the expression of some thermodynamic functions depending on the complex wave number. This allows to the determination of very important rheological properties of the aforementioned materials and the explanation of how they react to frequency dependent ultrasound perturbation. We noted that the stress is greater in the solution of erythrocytes compared to whole blood but this difference is reduced as we approach to 108 Hz. These observations, in red blood cells solution might be due to lack of “oncotic protection” exerted by plasma proteins (albumin, ceruloplasmin) but when the frequency increases the same proteins precipitate because they lose their native folding resulting in the increase of whole blood viscosity. We could define 6.107 Hz as the threshold value beyond which in whole blood the ultrasonic waves cause the triggering of the phenomenon and the plasmatic proteins as a sort of “lubricant agents” that protect erythrocytes by the environmental perturbations. This work represents a preliminary part of wider results that we would like to achieve to the purpose of determining the threshold values of the macromolecular stability of a particular tissue as the human blood in response to dynamic stress.

Exercise-induced changes in hematocrit and hematocrit/viscosity ratio in male rugby players

We investigated whether the concept of hematocrit/viscosity (h/η) ratio explains the "paradox of hematocrit in athletes", by calculating a "theoretical optimal hematocrit" (i.e., associated with the higher h/η value predicted with Quemada's equation from plasma viscosity, and erythrocyte rigidity index) before and after exercise. 14 rugby players (19-31 yr; weight 65.8-109.2 kg; height 1.7-1.96 m; BMI 21.7-33.1 kg/m2) underwent a standardized submaximal exercise session on cycloergometer corresponding to 225 kjoules over 30 min. The rheologic response to exercise was measured with the MT90 viscometer and the Myrenne aggregometer. After exercise there was an increase in whole blood viscosity (p < 0.05) and hematocrit (p < 0.005) and a decrease in h/η ratio (from 14.7±0.34 to 12.9±0.37, p < 0.005). There was an increase in viscometric RBC rigidity indexes "Tk" and "k" in 9/14 subjects. Predicted and actual h/η are fairly well correlated (preexercise r = 0.998, p < 0.001; postexercise r = 0.985 p < 0.001) but actual h/η was lower than predicted (preexercise p = 0.005; postexercise p = 0.02). This discrepancy between predicted and measured hematocrit was not correlated to dehydration or plasma viscosity but was correlated to red cell rigidity (r = 0.774, p < 0.01) and its exercise-induced change (r = 0.858, p < 0.01). This study suggests that h/η, although it is not directly correlated to parameters of exercise performance, is precisely regulated during exercise according to the classic concept of "viscoregulation", and that the prediction of the theoretical optimal values of h/η and hematocrit by models may help to interpret the actual values of these parameters. However, these models need to be more extendedly tested and improved.

Cyanotic congenital heart disease (CCHD): focus on hypoxemia, secondary erythrocytosis, and coagulation alterations.

Children with cyanotic congenital heart disease (CCHD) have complex alterations in their whole blood composition and coagulation profile due to long-standing hypoxemia. Secondary erythrocytosis is an associated physiological response intended to increase circulating red blood cells and oxygen carrying capacity. However, this response is frequently offset by an increase in whole blood viscosity that paradoxically reduces blood flow and tissue perfusion. In addition, the accompanying reduction in plasma volume leads to significant deficiencies in multiple coagulation proteins including platelets, fibrinogen and other clotting factors. On the one hand, these patients may suffer from severe hyperviscosity and subclinical 'sludging' in the peripheral vasculature with an increased risk of thrombosis. On the other hand, they are at an increased risk for postoperative hemorrhage due to a complex derangement in their hemostatic profile. Anesthesiologists caring for children with CCHD and secondary erythrocytosis need to understand the pathophysiology of these alterations and be aware of available strategies that lessen the risk of bleeding and/or thrombosis. The aim of this review is to provide an updated analysis of the systemic effects of long-standing hypoxemia in children with primary congenital heart disease with a specific focus on secondary erythrocytosis and hemostasis.

Obesity-related increase in whole blood viscosity includes different profiles according to fat localization

In a precedent study we observed that overall adiposity evaluated with the body mass index (BMI) was correlated with plasma viscosity and red blood cells (RBC) aggregation while abdominal obesity as assessed with the waist to hip ratio (WHR) was correlated with hematocrit. We investigated this issue in 129 women (age 15-65 years, BMI: 15 to 44 kg/m(2), WHR: 0.65 to 1.13, fatness: 12-58%) who were divided into fatness groups: 17 underweight women (BMI <18.5), 75 normal weigh (BMI 18.5-24.9), 11 overweight (BMI 25-29.9), and 26 obese (BMI >30) divided according to WHR into 13 lower body and 13 upper body obese women. Whole blood viscosity significantly increases across obesity classes, and is higher in upper body than in lower body obesity (2.84 ± 0.08 vs 3.29 ± 0.09 mPa.s, p < 0.05). The correlations between whole blood viscosity and BMI (r = 0.383 p < 0.01) and WHR (r = 0.364 p < 0.01) are found again. The former is explained by correlations of BMI with plasma viscosity (r = 0.303 p < 0.01) and red cell rigidity (r = 0.356 p < 0.01) and the latter is only explained by a correlation between WHR and hematocrit (r = 0.524 p < 0.01). BMI is also correlated with RBC aggregation parameters. Actually, when total fatness is evaluated with the percentage of fat (%fat) given by bioimpedance analysis (BIA), the picture is slightly different, since %fat is correlated with whole blood viscosity and RBC aggregation parameters but not with hematocrit, plasma viscosity and red cell rigidity. Fat free mass is also correlated with whole blood viscosity (r = 0.227 p < 0.02) due to a correlation with hematocrit (r = 0.483 p < 0.01) but neither RBC rheology nor plasma viscosity. This study shows that fatness by its own is associated with increased red cell aggregation, that abdominal fat increases blood viscosity due to a rise in hematocrit, and that overall body size as assessed with the BMI is associated with increased plasma viscosity and red cell rigidity.

Rapid Decrease in Overall Tumor Burden On Ibrutinib (PCI-32765) in CLL Despite Transient Increase in ALC Indicates a Significant Degree of Treatment Induced Cell Death.

AbstractAbstract 2899 Introduction:Bruton's tyrosine kinase (BTK) is essential for B cell receptor (BCR) signaling. Ibrutinib (PCI 32765) is a covalent inhibitor of BTK that has demonstrated durable antitumor activity in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (Byrd ASCO 2011, O'Brien ASH 2011). Ibrutinib induces a transient increase in the absolute lymphocyte count (ALC) occurring during a period of rapid reduction in lymphadenopathy. This is thought to be due to inhibition of CLL cell adhesion and migration leading to a release of CLL cells from tissue sites. Patients and Methods:This phase II trial (NCT01500733) using ibrutinib 420 mg daily on 28 day cycles enrolled two cohorts of CLL/SLL patients; 1.) >65 years old; and 2.) having deletion of chromosome 17p). Treatment naive and previously treated patients in need of treatment were eligible. Response was assessed after 2 cycles using CT scans. Bone marrow (BM) biopsies in a subset of patients were obtained at baseline and either on day 28 or 56. Whole blood viscosity was measured. Here we report on effects of ibrutinib in 26 patients (n=11, >65 yo; n=15, del 17p) who completed >2 cycles. Results:Fourteen patients (54%) had a partial response (PR) by IWCLL criteria, and 62% achieved a >50% reduction in lymphadenopathy measured as the sum of the products of the greatest diameter (SPD) of the 4 largest lymph nodes as assessed by CT, irrespective of ALC. The effects of ibrutinib on total tumor burden were measured by concomitantly assessing lymph node (LN), spleen, blood, and BM disease. The median reduction in lymphadenopathy was 52% (range 22–72%) on day 56. Despite at times massive reduction in tumor burden, there was no evidence of tumor lysis. The rates of nodal responses in subgroups of patients defined by deletion 17p, non deletion 17p, treatment naive and relapsed/refractory patients was comparable. There was an overall reduction in splenic disease with a median decrease in spleen size (measured as longest cranio-caudal extension) of 11% (0.5–40%; P<0.01). A trend towards more rapid resolution of splenomegaly in treatment naïve patients was seen. BM evaluations are complete in 10 patients: cellularity decreased in 3 of 7 and remained unchanged in 4 on day 28; on day 56 cellularity was decreased in 3 of 3 patients. Using immunohistochemistry for CD79 we confirmed that the reduction in BM infiltration was due to reduced tumor infiltration. As seen in other studies, the increase in ALC peaked within the first 2 months followed by a slow decline. The median ALC increased from 75 k/μl (3.5 – 308) to 102 k/μl on day 28 (P<.01). However, only 62% of patients had an increased ALC on treatment days 14 and 28 compared to baseline and the change in ALC at the end of the first cycle (day 28) was very heterogeneous (>95% reduction to ∼700% increase). Treatment naïve patients showed more pronounced relative increases in ALC and the most dramatic increase occurred in patients with a lower starting ALC. The rise in ALC correlated with an increase in whole blood viscosity (r=0.52; P<0.05, n=18). However, all viscosity measurements, both at baseline and on treatment, were within the normal range (3.6–6.0 cP) and there were no clinical signs or symptoms of a hyperviscosity syndrome. Conclusion:Reduction in lymphadenopathy with a transient increase in ALC has been reported in other studies and is thought to reflect a redistribution of tumor burden into the blood. While a treatment induced rise in ALC was common in our patients, up to a third had resolution of blood disease within a few weeks. This and the often dramatic reduction in nodal disease with or without an increase in ALC, and the concomitant reduction in tumor infiltration of BM and spleen indicate a significant contribution of cell death, the mechanism of which remains to be defined. Interestingly resolution of disease in the BM appears to be slower than in the LN. This may reflect more active BCR signaling in the LN and consequently more pronounced changes in tumor biology on ibrutinib in this site. In addition, treatment naïve patients appear to respond more rapidly raising the question whether untreated CLL is more dependent on BTK-dependent signaling pathways in the tissue microenvironment.This work was supported by the Intramural Research Program of NHLBI, NIH. We thank our patients for participating in these research studies. Disclosures:No relevant conflicts of interest to declare.

Effect of Congrong powder preparation on erythrocyte parameter and index of blood rheology in rats

To observe the effect of Congrong powder preparation on erythrocyte parameter and the index of blood rheology in healthy rats. The 50 rats were randomly divided into 5 groups ( physiological saline group, testosterone propionate group, large-dose administered group, moderate-dose administered group, small-dose administered group). Blood were taken to determine erythrocyte parameter and the index of blood rheology. Congrong powder preparation had no effect on erythrocyte parameter. There was an increase in whole blood viscosity, whole blood reduction viscosity, and in the erythrocyte rigidity index in the large-dose administered group. Congrong powder can influence deformability and some related characters of erythrocytes.

In Vivo Shear Stress Determines Circulating Levels of Endothelial Microparticles in End-Stage Renal Disease

Shear stress is a major determinant of endothelial apoptosis, but its role in the in vivo release of shed membrane microparticles by endothelial cells remains unknown. Thus, we sought to evaluate the possible relationship between circulating endothelial microparticle levels and laminar shear stress in end-stage renal disease patients with high cardiovascular risk, whose levels of endothelial microparticles are elevated. In 34 hemodialyzed patients, we analyzed the relationships between brachial artery and aortic shear stress and circulating microparticles levels. Only endothelial microparticles were inversely correlated with laminar shear stress values (P<0.0001) or its components shear rate and whole blood viscosity, independent of age or arterial blood pressure. Changes in hematocrit resulting from hemodialysis-induced hemoconcentration or erythropoietin anemia improvement induced a significant increase in whole blood viscosity and shear stress and were associated with a significant decrease in endothelial microparticles with a significant and inverse correlation with changes in hematocrit/hemoglobin or laminar shear stress. These results demonstrate that, in end-stage renal disease patients, laminar shear stress is an important determinant of plasma levels of endothelial microparticles. Anemia as an important determinant of whole blood viscosity and shear stress, contributes to endothelial apoptosis, and could play an indirect role in the pathogenesis of accelerated arteriosclerosis in this high-risk population.

Blood Rheology in PCA and PCEA After Total Knee Arthroplasty

The rheological events in 2 groups of patients undergoing total knee arthroplasty were compared—15 patients were given general anesthesia and controlled their postoperative pain applying intravenous patient-controlled analgesia; 17 individuals received combined spinal-epidural anesthesia and controlled their postoperative pain by patient-controlled epidural analgesia (PCEA). Twenty-four and 48 hours after surgery, the patient-controlled analgesia group showed a significant increase in whole-blood viscosity at the 3 shear rates ( P < .01), as well as in relative viscosity at both periods ( P < .001 and .01, respectively). Similar findings were observed for red blood cell aggregation ( P < .001) and fibrinogen level ( P < .001). These values were less expressed in the PCEA group, particularly 48 hours after surgery ( P < .01), and the patients showed lower scores on the visual analog pain scale. The better results observed in the PCEA group favor the application of epidural anesthesia and PCEA analgesia in patients undergoing total knee arthroplasty.

Pentoxifylline Attenuates the Increase in Whole Blood Viscosity After Transfusion

Pentoxifylline Attenuates the Increase in Whole Blood Viscosity After Transfusion

Haemorheology in Exercise and Training

Disruption of the normal rheological properties of blood is considered an independent risk factor for cardiovascular disease and plays a significant role in the aetiology of atherothrombogenesis. The acute increase in whole blood viscosity may unfavourably affect the microcirculatory blood flow and oxygen delivery to the tissues. It is universally accepted that exercise and physical activity performed on a regular basis has health benefits. However, the effects of exercise on the rheological properties of blood have not received much research attention. Recent, limited evidence indicates that the viscosities of whole blood and plasma increase in response to a variety of exercise protocols. The increase in whole blood viscosity is mainly attributed to an increase in haematocrit and plasma viscosity, whereas the deformability and aggregability of red blood cells remain unaltered. The increases in plasma viscosity and haematocrit have been ascribed to exercise-induced haemoconcentration as a result of fluid transfer from the blood to the interstitial spaces. The haemorheological changes associated with strenuous exercise appear to be linked with enhanced oxidative stress and depletion of antioxidant capacity, and that may affect oxygen delivery and availability to the tissues. Although significant advances have been made in many areas of exercise haematology, the long-term effects of endurance training on blood rheology have been very briefly examined and the exact effect of training has not as yet been determined. Available cross-sectional and longitudinal studies indicate that the blood of endurance athletes is more dilute and this has been attributed to an expansion of blood volume, particularly plasma volume as a result of training. The low haematocrit values in trained athletes represent a hydration condition rather than iron stores deficiency. It has been suggested that this hypervolaemia and blood dilutional effect of endurance training may be advantageous for heat dissipation and greater cardiac stroke volume and lower heart rates during exercise. Enhanced blood fluidity also facilitates oxygen delivery to the exercising muscles because of a reduced resistance to blood flow within the microcirculation. Furthermore, the increase in plasma volume may contribute to the body water pool and help offset dehydration. The influence of strength and power training on blood rheology is not known. The physiological mechanisms responsible for and the functional consequences of the haemorheological changes associated with exercise to a large extent remain speculative. The paradox of haematocrit and blood rheology in exercise and training warrants additional studies. Likewise, further investigations are necessary to determine the possible link between overtraining and blood rheological profiles.

Pentoxifylline attenuates the increase in whole blood viscosity after transfusion

Pentoxifylline improves tissue oxygenation and intestinal blood flow in models of haemorrhagic shock, and it has been used for the treatment of intermittent claudication due to its beneficial effects on haemorheology. We investigated the effects of pentoxifylline on whole blood viscosity during packed red-blood cell transfusion in critically ill adult patients. Twenty critically ill patients were randomly assigned to one of two groups (pentoxifylline group: n = 11, placebo group: n = 9) and prospectively studied. Forty-five minutes before and during the packed red-blood cell transfusion (10 ml min(-1)) over a period of 80 min, 1.5 mg kg(-1) . h(-1) pentoxifylline or placebo were administered intravenously. Haematocrit, plasma fibrinogen concentration, total protein concentration, whole blood viscosity (at a shear rate of 10 s(-1), 50 s(-1), and 100 s(-1)) and plasma viscosity were measured. After the packed red-blood cell transfusion, haematocrit levels increased significantly in both groups (pentoxifylline group: from 26.1 +/- 2.8% to 33.0 +/- 3.2; placebo group: from 24.4 +/- 3.3% to 32.6 +/- 2.6%; means +/- standard deviation). Compared to baseline, whole blood viscosity increased in both groups at all shear rates after the transfusion, but the increase was significantly less in the pentoxifylline group (26 +/- 15% vs. 49 +/- 14%, 23 +/- 11% vs. 39 +/- 12%, and 22 +/- 11% vs. 35 +/- 12% for the pentoxifylline vs. placebo groups at shear rates of 10 s(-1), 50 s(-1), and 100 s(-1), respectively). Plasma viscosity, total protein concentration, and fibrinogen concentration remained unchanged and no significant differences among groups were observed. These results suggest that pentoxifylline is effective in attenuating the increase in whole blood viscosity after a transfusion of packed red-blood cells. Plasma viscosity is not influenced by pentoxifylline.

Commercial taxane formulations induce stomatocytosis and increase blood viscosity.

1. Taxanes are antineoplastic drugs which have cardiovascular side effects of unknown mechanism. We investigated their influence on blood viscosity and erythrocyte morphology. 2. Whole blood was incubated in vitro with increasing concentrations of Taxol, Taxotere, paclitaxel (0-100 microM) and the vehicles Cremophor-EL and Tween 80 (0-5% vol) for 1 h at 37 degrees C. Plasma and whole blood viscosity (Haematocrit 45%) were measured and erythrocyte morphology was assessed on glutaraldehyde-fixed cells. The same investigations were performed in seven patients before and after a Taxol-infusion. 3. Taxol and Taxotere induced a dose- and time-dependent stomatocytic shape transformation of erythrocytes. Paclitaxel alone had no effect, but the vehicles cremophor-EL and Tween 80, used in Taxol and Taxotere, respectively, induced a comparable degree of stomatocytosis. This suggests a preferential intercalation of these substances into the inner hemileaflet of the membrane lipid bilayer. Associated with this shape change a dose-dependent increase in plasma and whole blood viscosity was observed. Neither shape nor viscosity changes were reversible upon removal of the agents. After the infusion of 130-300 mg Taxol in patients a slight shift towards stomatocytosis and an increase in whole blood viscosity at high shear rate from 5.09+/-0.30 to 5.44+/-0.38 mPa.s (P<0.05) were confirmed. 4. Commercial taxane drug formulations induce stomatocytosis and increase blood viscosity, which is due to their formulation vehicles. These findings may contribute to the understanding of the cardiovascular side effects of these drugs.

Cold acclimation-induced increase of systolic blood pressure in rats is associated with volume expansion

To investigate the mechanisms of cold-induced hypertension, the systolic blood pressure (SBP) and average daily water consumption were measured weekly in 6-month-old male Wistar rats; they were subsequently acclimated to thermoneutrality (26°C for 7 weeks), to cold temperature (6°C for 9 weeks), and then again reacclimated to 26°C for 5 weeks. Circulating plasma volume and whole blood viscosity were measured in subgroups of rats at the end of acclimation to 26°C after 2 days, after 1, 6, and 8 weeks of cold, and after 2 and 5 weeks of rewarming. The control values obtained at the end of thermoneutral period were: SBP = 130.8 ±18.6 mm Hg, plasma volume = 41.9 ± 4.64 mL/kg, whole body viscosity at shear rate of 22.5 per sec = 6.7 ± 0.48 cps, and daily water consumption = 42.25 ± 16.81 mL. After 48 h of cold exposure there was almost a 50% increase in plasma volume that persisted to a lesser degree throughout the whole period of cold exposure ( P < .05). After 2 weeks of cold exposure the daily water consumption increased and SBP began to increase. After 6 weeks of cold exposure the SBP was 30 mm Hg above that of the control level ( P < .001) and was accompanied by a 25% increase in whole blood viscosity ( P < .05). At the end of 8 weeks of cold exposure the plasma volume was 56.8 ± 9.51 mL/kg and the whole blood viscosity was 8.0 ± 1.79 cps at the 22.5 per sec shear rate. During the 5 weeks of rewarming the elevation of SBP and increased whole blood viscosity persisted, whereas the increased daily water consumption and expanded plasma volume returned to normal. Therefore, the acclimation to cold is accompanied by the development of a volume-associated hypertension, which is sustained after rewarming without volume expansion.

Effects of exercise and training on blood rheology.

The effects of exercise on the rheological properties of blood have not received much research attention. Recent, limited evidence indicates that the viscosities of whole blood and plasma increase in response to a variety of exercise protocols. The increase in whole blood viscosity is mainly attributed to an increase in haematocrit and plasma viscosity, whereas the deformability and aggregability of red blood cells remain unaltered. The increases in plasma viscosity and haematocrit have been ascribed to exercise-induced haemoconcentration as a result of fluid transfer from the blood to the interstitial spaces. Although the long term effects of endurance training on blood rheology have been very briefly examined, the exact effect of training has not as yet been determined. However, available cross-sectional and longitudinal studies indicate that the blood of endurance athletes is more dilute and this has been attributed to an expansion of plasma volume as a result of training. It has been suggested that this blood dilutional effect of endurance training may be advantageous in delivering oxygen to the exercising muscles because of a reduced resistance to blood flow. The increase in plasma volume may also contribute to the body water pool and help offset dehydration. The influence of strength and power training on blood rheology is not known.