Posttransfusion Increase of Hematocrit per se Does Not Improve Circulatory Oxygen Delivery due to Increased Blood Viscosity.

Background: Blood transfusion is used to treat acute anemia with the goal of increasing blood oxygen-carrying capacity as determined by hematocrit (Hct) and oxygen delivery (DO2). However, increasing Hct also increases blood viscosity, which may thus lower DO2 if the arterial circulation is a rigid hydraulic system as the resistance to blood flow will increase. The net effect of transfusion on DO2 in this system can be analyzed by using the relationship between Hct and systemic blood viscosity of circulating blood at the posttransfusion Hct to calculate DO2 and comparing this value with pretransfusion DO2.

Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients.

Morbid obesity has been shown to increase the risk to develop hepatic steatosis, also referred to as non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that the severity of NAFLD may associate with increased serum levels of inflammatory markers as well as decreased concentration of mediators with anti-inflammatory actions, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL) 10, respectively. We thus examined the serum levels of TNF-α and IL-10 in 102 morbidly obese women and men (body mass index > 40 kg/m(2)), exhibiting different grades of NAFLD.

Supra-plasma expanders: the future of treating blood loss and anemia without red cell transfusions?

Oxygen delivery capacity during profoundly anemic conditions depends on blood's oxygen-carrying capacity and cardiac output. Oxygen-carrying blood substitutes and blood transfusion augment oxygen-carrying capacity, but both have given rise to safety concerns, and their efficacy remains unresolved. Anemia decreases oxygen-carrying capacity and blood viscosity.

Replacing the Transfusion of 1-2 Units of Blood with Plasma Expanders that Increase Oxygen Delivery Capacity: Evidence from Experimental Studies.

At least a third of the blood supply in the world is used to transfuse 1-2 units of packed red blood cells for each intervention and most clinical trials of blood substitutes have been carried out at this level of oxygen carrying capacity (OCC) restoration. However, the increase of oxygenation achieved is marginal or none at all for molecular hemoglobin (Hb) products, due to their lingering vasoactivity. This has provided the impetus for the development of "oxygen therapeutics" using Hb-based molecules that have high oxygen affinity and target delivery of oxygen to anoxic areas.

Influence of serological factors and BMI on the blood pressure/hematocrit association in healthy young men and women.

The association between mean arterial blood pressure (MAP) and hematocrit (Hct) as a surrogate for blood viscosity was investigated in a young (average 20.0±2.3 years), healthy population of 174 men and 442 women.

Semisynthetic hybrid biopolymers for non-pharmacological intervention of the microcirculation.

The microcirculation presents functional organic structures in the range of 1-100 micrometers, commensurate with the upper end of nanotechnology constructs. When devices are designed and deployed to deliver treatment via the circulation they ultimately contend with the smallest dimensions of both healthy and impaired microvessels, particularly the capillary system whose ability to sustain the tissue is assessed by measuring "functional capillary density" (FCD). FCD is directly determined by hydrostatic and osmotic pressures and indirectly by the effect of cardiovascular regulators, particularly the bioavailability of nitric oxide (NO) resulting from fluid mechanical effects and transport in the submicroscopic cell free plasma layer (CFL) located between blood and microvascular wall.

Autoregulation and mechanotransduction control the arteriolar response to small changes in hematocrit.

Here, we present an analytic model of arteriolar mechanics that accounts for key autoregulation mechanisms, including the myogenic response and the vasodilatory effects of nitric oxide (NO) in the vasculature. It couples the fluid mechanics of blood flow in arterioles with solid mechanics of the vessel wall and includes the effects of wall shear stress- and stretch-induced endothelial NO production. The model can be used to describe the regulation of blood flow and NO transport under small changes in hematocrit and to analyze the regulatory response of arterioles to small changes in hematocrit.

PEG-albumin plasma expansion increases expression of MCP-1 evidencing increased circulatory wall shear stress: an experimental study.

Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS), decreasing endothelial nitric oxide (NO) production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb) causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic.

Plasma expander and blood storage effects on capillary perfusion in transfusion after hemorrhage.

Background: Treating hemorrhage with blood transfusions in subjects previously hemodiluted with different colloidal plasma expanders, using fresh autologous blood or blood that has been stored for 2 weeks, allows identifying the interaction between type of plasma expander and differences in blood storage.

Study Design And Methods: Studies used the hamster window chamber model. Fresh autologous plasma, 130-kDa starch-based plasma expander (hydroxyethyl starch [HES]), or 4% polyethylene glycol-conjugated albumin (PEG-Alb) was used for 20% of blood volume (BV) hemodilution.

Blood pressure and blood viscosity are not correlated in normal healthy subjects.

The relationship between blood viscosity, hematocrit (Hct), and mean arterial blood pressure (MAP) was studied in a healthy population of 91 men and 66 women with an average age of 30.6 ± 8.0 years, from the city of Victoria de Durango (1800 m elevation).

Nonlinear cardiovascular regulation consequent to changes in blood viscosity.

Increasing blood and plasma viscosity is generally associated with pathological conditions, and increased cardiovascular risk, a perception based in part on studies where blood viscosity is increased to extreme values attained by hemoconcentration. Present studies, supported by epidemiological studies in humans, show that moderate increases in Hct improve cardiovascular function and vice versa. This result is due to the nonlinear regulation of peripheral vascular resistance arising from the increased production of nitric oxide following the increase of shear stress on the vascular wall due to increasing blood viscosity.

Incident prediabetes/diabetes and blood pressure in urban and rural communities in the Democratic Republic of Congo.

Background: The Democratic Republic of Congo (DRC) faces increased morbidity and mortality due to treatable and preventable noncommunicable diseases. However, it continues to struggle with political and economic instability, which impedes much needed health infrastructure improvements. The present study was designed as a low-cost determination of the prevalence of incident prediabetes/diabetes in the DRC.

Effect of plasma expander viscosity on the cell free layer.

The effect of low and high viscosity hemodilution with plasma expanders on the extent of the cell free layer (CFL) width was analyzed in the microcirculation of the exteriorized cremaster muscle preparation of Sprague-Dawley male rats. Anesthetized animals were subjected to 40% hemodilution by blood volume, using 5% human serum albumin (HSA) or 6% Hetastarch (hydroxyethyl starch 670 kDa). Arterioles (n=5 for each treatment) were investigated.

Integration of cardiovascular regulation by the blood/endothelium cell-free layer.

The cell-free layer (CFL) width separating red blood cells in flowing blood from the endothelial cell membrane is shown to be a regulator of the balance between nitric oxide (NO) production by the endothelium and NO scavenging by blood hemoglobin. The CFL width is determined by hematocrit (Hct) and the vessel wall flow velocity gradient. These factors and blood and plasma viscosity determine vessel wall shear stress which regulates the production of NO in the vascular wall.

Vasoactive hemoglobin solution improves survival in hemodilution followed by hemorrhagic shock.

Objective: To compare survival after exchange transfusion followed by hemorrhage using: 1) the vasoactive, oxygen-carrying, bovine hemoglobin-based blood substitute Oxyglobin (Biopure, 12.9 g hemoglobin/dL); and 2) the hydroxyethyl starch plasma expander Hextend (high molecular weight and low degree of substitution, 6%).

Design: Comparison between treatments.

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.

The variability of blood pressure due to small changes of hematocrit.

The hematocrit (Hct) of awake hamsters was lowered to 90% of baseline by isovolemic hemodilution using hamster plasma to determine the acute effect of small changes in Hct and blood viscosity on systemic hemodynamics. Mean arterial blood pressure increased, reaching a maximum of about 10% above baseline (8.6 +/- 5.

The effect of small changes in hematocrit on nitric oxide transport in arterioles.

We report the development of a mathematical model that quantifies the effects of small changes in systemic hematocrit (Hct) on the transport of nitric oxide (NO) in the microcirculation. The model consists of coupled transport equations for NO and oxygen (O2) and accounts for both shear-induced NO production by the endothelium and the effect of changing systemic Hct on the rate of NO production and the rate of NO scavenging by red blood cells. To incorporate the dependence of the plasma layer width on changes in Hct, the model couples the hemodynamics of blood in arterioles with NO and O2 transport in the plasma layer.

Functional optical imaging at the microscopic level.

Functional microscopic imaging of in vivo tissues aims at characterizing parameters at the level of the unitary cellular components under normal conditions, in the presence of blood flow, to understand and monitor phenomena that lead to maintaining homeostatic balance. Of principal interest are the setting of shear stress on the endothelium; formation of the plasma layer, where the balance between nitric oxide production and scavenging is established; and formation of the oxygen gradients that determine the distribution of oxygen from blood into the tissue. Optical techniques that enable the analysis of functional microvascular processes are the measurement of blood vessel dimensions by image shearing, the photometric analysis of the extent of the plasma layer, the dual-slit methodology for measuring blood flow velocity, and the direct measurement of oxygen concentration in blood and tissue.

Blood pressure directly correlates with blood viscosity in diabetes type 1 children but not in normals.

Objective: To determine the relationship between mean arterial blood pressure (MAP) and blood viscosity in diabetic type 1 children and healthy controls to investigate whether MAP is independent of blood viscosity in healthy children, and vice versa.

Research Design And Methods: Children with diabetes type 1 treated by insulin injection were studied. Controls were healthy children of both sexes.

Seasonal hematocrit variation and health risks in the adult population of Kinshasa, Democratic Republic of Congo.

Hematocrit (Hct) as an indicator of blood viscosity and mean arterial blood pressure (MAP) were assessed according to the season in adult participants of health screenings conducted throughout Kinshasa, Democratic Republic of Congo. Data was collected at the end of summer (April) and the end of winter (August) and identified by gender. Male Hcts in August were significantly higher (P < 0.

Hematocrit and mean arterial blood pressure in pre- and postmenopause women.

The relationship between mean arterial blood pressure (MAP) and hematocrit (Hct) was studied in pre- and postmenopause women in the city of Durango, Mexico. Premenopause women show a negative trend between parameters that is not statistically significant. MAP and Hct are directly related in postmenopause women (p < 0.

Microcirculatory effects of intravenous fluids in critical illness: plasma expansion beyond crystalloids and colloids.

Purpose Of Review: Plasma expanders are reviewed to determine their ability to restore microvascular function as a means for extending the transfusion trigger and delaying the use of blood transfusions. This outcome is currently achievable because of the emergence of a new understanding of optimal tissue function that prioritizes maintenance of functional capillary density, which results from the normalization of blood viscosity via the increase in plasma viscosity with new viscogenic colloids.

Recent Findings: Use of viscous plasma expanders in experimental models of extreme hemodilution, hemorrhagic shock and endotoxemia shows that the limiting factor in anemia is not oxygen-carrying capacity but the decline of microvascular function due to the lowering of functional capillary density.

Microvascular experimental evidence on the relative significance of restoring oxygen carrying capacity vs. blood viscosity in shock resuscitation.

The development of volume replacement fluids for resuscitation in hemorrhagic shock comprises oxygen carrying and non carrying fluids. Non oxygen carrying fluids or plasma expanders are used up to the transfusion trigger, and upon reaching this landmark either blood, and possibly in the near future oxygen carrying blood substitutes, are used. An experimental program in hemorrhagic shock using the hamster chamber window model allowed to compare the relative performance of most fluids proposed for shock resuscitation.

Increased hematocrit and reduced blood pressure following control of glycemia in diabetes.

In this study we determine the effects of reducing blood glucose on mean arterial blood pressure (MAP) and hematocrit (Hct) in patients with type 2 diabetes who are not responding to conventional treatment in an intensive treatment program 1 year after initiation of treatment. Data on MAP, glucose and Hct was obtained from 21 diabetic type 2 individuals subjected to personalized treatment and compared (paired statistics) to pretreatment conditions. Exclusion criteria were severe retinopathy, diabetic nephropathy, amputation of diabetic foot and increased glucose>50 mg/dl.