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There is a 0.138% incidence of adverse reactions related to blood transfusion. Transfusion-related acute lung injury, immunosuppression, fever, pathogen transmission, and hemolytic transfusion reactions are the most common ones. Synthetic oxygen carriers have been developed to deal with blood shortages and for use in the field where stored blood was not available. They were also designed to be pathogen free, including unknown viruses. In this study, we used Male Golden Syrian Hamsters implemented with a dorsal window chamber to determine how infusion of three different, genetically crosslinked recombinant acellular hemoglobin (rHb) solutions with different oxygen affinities and nitric oxide kinetics affect mean arterial pressure (MAP), heart rate (HR), kidney function, and kidney structure. We found that the administration of all three rHb solutions caused mild hypertension and bradycardia 30 minutes after infusion. However, acute changes in glomerular filtration rate (GFR) were not detected, even though histological analysis was performed 72 hours after treatment revealed some structural changes. All the rHb solutions resulted in hypertension 30 minutes after a 10% topload administration. Regardless of their properties, the presence of acellular Hb causes significant alterations to kidney tissue.

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Background: Diuretics are the first choice as an antihypertensive, because of its efficacy and cost, however its mechanism of action is not well understood. The aim of this work was to analyze the hemorrheological effect of the diuretics as vasodilators in patients with newly diagnosed arterial hypertension. Methods: Patients with hypertension were given diet and exercise recommendations and 25 mg of chlorthalidone per day were prescribed; Hemoglobin/hematocrit, viscosity, and basal nitric oxide (ON) were determined at 15 and 45 days and compared with healthy subjects. Results: We included 28 patients with average age of 48 years old; systolic blood pressure in the treated patients decreased from baseline at 15 days from 130 to 119 mm Hg and at 114 mmHg at 15 to 45 days; diastolic blood pressure decreased from baseline at 15 days from 103 to 97 mm Hg, and at 93 mmHg at 15 to 45 days. The hematocrit increased in both men and women with a statistical significance of the baseline period at 15 days, after that, it remained without significative changes. The viscosity increased similarly to the hematocrit, which conditioned the ON elevation. Conclusions: The increase in hematocrit due to diuretic caused an increase in blood viscosity, which led to an increase in nitric oxide, resulting in lower blood pressure.

Introducción: Los diuréticos son la primera elección como antihipertensivo por su eficacia y costo, sin embargo su mecanismo de acción no está bien esclarecido. El objetivo de este trabajo fue analizar el efecto hemorreológico del diurético como vasodilatador en pacientes con hipertensión arterial de reciente diagnóstico. Métodos: A los pacientes con hipertensión arterial se les dieron recomendaciones de dieta, ejercicio y se prescribió 25 mg de clortalidona al día; se determinaron hemoglobina/hematocrito, viscosidad y óxido nítrico (ON) basal, a los 15 y 45 días y se compararon con sujetos sanos. Resultados: Se incluyeron 28 pacientes, con edad promedio de 48 años; la presión arterial sistólica en los pacientes tratados descendió de la cifra basal a los 15 días de 130 a 119 mmHg, y a 114 mmHg de los 15 a los 45 días; la presión arterial diastólica descendió de la basal a los 15 días de 103 a 97 mmHg, y a 93 mmHg de los 15 a los 45 días . El hematocrito se incrementó en ambos géneros, con significancia estadística del período basal a los 15 días de tratamiento, posteriormente permaneció sin cambios. La viscosidad se incrementó de forma similar al hematocrito, lo que condicionó elevación del ON. Conclusiones: El incremento del hematocrito debido al diurético causó elevación de la viscosidad sanguínea, lo que condujo a incremento del óxido nítrico, repercutiendo en el descenso de la presión arterial.

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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. Macromolecules using colloids as templates that are surface decorated with polyethylene glycol (PEG) become immuno-invisible and can be introduced into the circulation to manipulate the NO environment in blood and the endothelium. PEG-albumin is a class of molecules with novel plasma expansion properties that directly interacts with the microcirculation via CFL related effects. The principal application of this technology is in transfusion medicine and the plasma expanders used to treat blood losses and concomitant effects on microvascular function due to related acute inflammatory conditions and ischemia.

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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 +/- 5.5 mmHg) when Hct decreased 8.4 +/- 1.9% (P < 0.005). Cardiac output increased continuously with hemodilution. These conditions were reached at approximately 60 min after exchange transfusion and remained stationary for 1 h. Peripheral vascular resistance was approximately constant up to a decrease of Hct of about 10% and then fell continuously with lowering Hct. Vascular hindrance or vascular resistance independent of blood viscosity increased by about 20% and remained at this level up to an Hct decrease of 20%, indicating that the vasculature constricted with the lowered Hct. The results for the initial 2-h period are opposite but continuous with previous findings with small increases in Hct. In conclusion, limited acute anemic conditions increase mean arterial blood pressure during the initial period of 2 h, an effect that is quantitatively similar but opposite to the acute increase of Hct during the same period.

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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 < 0.01). It is proposed that that this MAP/Hct relationship is in part due to differences in endothelial function where menopause decreases the capacity of the endothelium to respond to increased blood viscosity and shears stress, leading to the increased production of vasodilator mediators to compensate for changes in blood viscosity due to changes in Hct. Comparison with a large group of postmenopause women in the city of Stockholm showed identical trends.

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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. In support of this hypothesis, we find that viscogenic colloids including high-molecular-weight starches, dextrans, polyvinylpyrrolidone, keratin and polyethylene glycol-conjugated albumin maintain or restore microvascular function in extreme hemodilution, polyethylene glycol-conjugated albumin yielding the best results. SUMMARY: Preclinical studies show that polyethylene glycol-conjugated albumin at concentrations in the range of 2-4% extends the transfusion trigger, providing the more extended and complete microvascular and systemic recovery from hemorrhagic shock, extreme hemodilution and endotoxemia, postponing the need of reestablish intrinsic blood oxygen-carrying capacity to hemoglobin concentrations lower than those associated with accepted transfusion triggers.

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Oxygen delivery and consumption after hemodilution with a perfluorocarbon-based oxygen carrier (PFCOC) was evaluated at sea level and at 2,600 m above sea level. Fifteen anesthetized rats were subjected to a two-exchange normovolemic hemodilution of 40% of the circulating blood volume each. First exchange was performed with a colloid solution. Second exchange was with 80% PFCOC and 20% colloid. Animals were then ventilated with 100% oxygen. Experiments were performed at barometric pressure of 1.0 atm (sea-level group, n=9) or 0.74 atm (2,600-m group, n=6). Blood gases, hematocrit, fluorocrit, and hemoglobin content were measured at baseline and 15 min after each exchange. After hemodilution, total arterial content was not modified by the PFCOC in either group. In contrast, arteriovenous oxygen difference increased significantly in both groups, as did the oxygen extraction ratio. In the second exchange, although total arterial content was similar between the two groups, the perfluorocarbon and plasma phases contributed significantly more at sea level. Arteriovenous oxygen difference was significantly less at sea level with a higher contribution from the perfluorocarbon and plasma phases. In conclusion, hemodilution with a PFCOC induced changes in oxygen delivery and consumption that differ with altitude. The 2,600-m group exhibited a higher oxygen extraction ratio and arteriovenous oxygen difference, with reduced oxygen delivery and unloading from both the fluorocarbon and plasma phase. Therefore, the efficacy of PFCOCs at 2,600 m above sea level is reduced, and altitude must be taken into account when PFCOCs are used.

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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. This model allows investigating simultaneously the microcirculation and systemic reactions, in the awake condition, in a tissue isolated from the environment. Results from this program show that in general plasma expanders such as Ringer's lactate and dextran 70 kDa do not sufficiently restore blood viscosity upon reaching the transfusion trigger, causing microvascular collapse. This is in part restored by a blood transfusion, independently of the oxygen carrying capacity of red blood cells. These results lead to the proposal that effective blood substitutes must be designed to prevent microvascular collapse, manifested in the decrease of functional capillary density. Achievement of this goal, in combination with the increase of oxygen affinity, significantly postpones the need for a blood transfusion, and lowers the total requirement of restoration of intrinsic oxygen carrying capacity.

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To determine the activated clotting time (ACT) in rats and hamsters from our colony and to evaluate the response of this parameter to different heparin doses in these species, ACTs were measured using a Medtronic HemoTec ACT measurement system in samples obtained by intracardiac puncture from normal, nonanticoagulated, anesthetized rats and hamsters. Another groups of animals received different intravenous boluses of heparin to determine the dose needed to maintain ACT values > 480 sec for at least 30 min. The ACT (mean +/- SEM) was 48.0 +/- 2.17 sec for the 50 rats sampled and 42.5 +/- 2.35 sec for the 48 hamsters. Rats required a bolus of 1200 IU/kg intravenous heparin to maintain an ACT > 480 sec for 30 min; hamsters required 1000 IU/kg heparin for the same effect. We concluded that compared with humans, rats and hamsters from our colony have short ACTs and low sensitivity to heparin, in terms of the dose needed to reach a target ACT as well as the time required to sustain it. Further the ACT values in these animals showed great variability.

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