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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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Perfluorocarbon (PFC) emulsions used as artificial oxygen carriers lack colloid osmotic pressure (COP) and must be administered with colloid-based plasma expanders (PEs). Although PFC emulsions have been widely studied, there is limited information about PFC emulsion interaction with PEs and blood. Their interaction forms aggregates due to electrostatic and rheological phenomena, and change blood rheology and blood flow. This study analyzes the effects of the interaction between PFC emulsions with blood in the presence of clinically-used PEs. The rheological behavior of the mixtures was analyzed in vitro in parallel with in vivo analysis of blood flow in the microcirculation using intravital microscopy, when PEs were administered in a clinically relevant scenario. The interaction between the PFC emulsion and PE with blood produced PFC droplets and red blood cell (RBCs) aggregation and increased blood viscosity in a shear dependent fashion. The PFC droplets formed aggregates when mixed with PEs containing electrolytes, and the aggregation increased with the electrolyte concentration. Mixtures of PFC with PEs that produced PFC aggregates also induced RCBs aggregation when mixed with blood, increasing blood viscosity at low shear rates. The more viscous suspension at low shear rates produced a blunted blood flow velocity profile in vivo compared to nonaggregating mixtures of PFC and PEs. For the PEs evaluated, human serum albumin produced minimal to undetectable aggregation. PFC and PEs interaction with blood can affect sections of the microcirculation with low shear rates (e.g., arterioles, venules, and pulmonary circulation) when used in a clinical setting, because persistent aggregates could cause capillary occlusion, decreased perfusion, pulmonary emboli or focal ischemia.

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Hextend® is a preparation of hetilstarch in a balanced electrolyte solution that contains 143 mEq/L of sodium, 124mEq/L of chloride, 5 mEq/L of calcium 3 mEq/L of potassium 0.9 mEq/L of magnesium, 0.99 g/L of glucose and 24 mEq/L of lactate. It has a volume of distribution similar to blood volume which enables it to stay in the intravascular compartment until it is renally cleared or absorbed by the reticuloendothelial system. It shows a bimodal pattern of clearance with a half life during the first 8 hrs of its infusion of 4.2 hrs and during the 7 days following of 38.2 hrs. Hextend® is currently one of the preferred resuscitation solutions in the hypovolemic patient showing a better profile of effects over hemostasis and acid base status and conferring a better survival over similar patients resuscitated with crystalloids or other synthetic colloids. Hextend® provides an adequate fluid that is effective in the resuscitation of the trauma patient in hypovolemic hemorrhagic shock and promises to become the fluid of choice in the routine management of these patients. There is a need of more randomized prospective studies in the field of trauma using Hextend ® and its combination with the inflammatory cascade modifiers such as ethyl pyruvate among others.

Hextend® es una combinación de hetilalmidón balanceada en una solución de electrolitos que contiene 143 mEq/L de sodio, 124 mEq/L de cloro, 5 mEq/L de calcio, 3 mEq/L de potasio, 0,9 mEq/L de magnesio, 0,99 g/L de glucosa y 24 mEq/L de lactato. Posee un volumen de distribución equivalente al volumen sanguíneo manteniéndose en el compartimento vascular hasta ser excretado vía renal o absorbido por el sistema retículo-endotelial. Estas características le confieren un patrón farmacocinético bimodal con una vida media de 4,2 horas durante las primeras 8 hrs de infusión y de 38,2 h durante los primeros 7 días. Hextend® es actualmente una de las soluciones de reanimación con mejor perfil de efectos sobre la hemostasia y el equilibrio ácido base del paciente en choque hipovolémico y confiere un aumento de la sobrevida, comparado con controles resucitados con cristaloides u otros coloides sintéticos. Esta combinación de hetilalmidón en una solución amortiguadora electrolítica posee mínimos efectos sobre la función hemostática y plaquetaria por lo que actualmente es preferido frente a soluciones cristaloides y otros coloides utilizados en el pasado en la reanimación de pacientes politraumatizados en estado de choque hipovolémico hemorrágico. A su vez, promete transformarse en el fluido de elección en el manejo rutinario de estos pacientes. En relación al uso de este producto es imperativo realizar un mayor número de estudios prospectivos randomizados. La literatura internacional augura un esplendoroso futuro al uso de Hextend®, como también a su posible combinación con modificadores de la cascada inflamatoria, entre otros con el etil piruvato.

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PURPOSE: The aim of this study was to show that 6% hydroxyethyl starch (HES) 130/0.4 achieves a better resuscitation of the microcirculation than normal saline solution (SS), during early goal-directed therapy (EGDT) in septic patients. MATERIALS AND METHODS: Patients with severe sepsis were randomized for EGDT with 6% HES 130/0.4 (n = 9) or SS (n = 11). Sublingual microcirculation was evaluated by sidestream dark field imaging 24 hours after the beginning of EGDT. RESULTS: On admission, there were no differences in Sequential Organ Failure Assessment score, mean arterial pressure, lactate, or central venous oxygen saturation. After 24 hours, no difference arose in those parameters. Sublingual capillary density was similar in both groups (21 ± 8 versus 20 ± 3 vessels/mm(2)); but capillary microvascular flow index, percent of perfused capillaries, and perfused capillary density were higher in 6% HES 130/0.4 (2.5 ± 0.5 versus 1.6 ± 0.7, 84 ± 15 versus 53 ± 26%, and 19 ± 6 versus 11 ± 5 vessels/mm(2), respectively, P < .005). CONCLUSIONS: Fluid resuscitation with 6% HES 130/0.4 may have advantages over SS to improve sublingual microcirculation. A greater number of patients would be necessary to confirm these findings.

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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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Acute normovolemic hemodilution (ANH) has been proposed to avoid the risks of allogenic transfusion. In reference to its cellular effects, ANH reports in the literature are scarce. Using electron microscopy (EM), we evaluated the effects of ANH on cardiac function and myocardial structure. Twenty-five dogs were prospectively randomized to a control group (n = 5) or to undergo ANH with 6% hydroxyethyl starch (HES; n = 10) or lactated Ringer's solution (LR; n = 10) administered, respectively, at a ratio of 1:1 or 1:3 to the volume of blood removed. Animals were gradually hemodiluted to a hematocrit of 10%, which was accomplished in 80 min. Pulmonary artery catheter and echocardiography were used to evaluate cardiac function. Myocardial samples were taken after the last time point for electron microscopy analysis. Data were obtained during five different stages of ANH, with a mean 20-min interval between each time point. Cardiac index increased significantly in both groups during ANH. A significant decrease in oxygen delivery and oxygen consumption, as well as an increase in oxygen extraction was verified in the LR group. Echocardiography demonstrated a decline in systolic function in the LR group at the end of the experiment. Electron microscopy analysis of the myocardium revealed slight lesions in cardiac cells in the HES group, and moderate-to-significant lesions in the LR group. In this animal species, ANH with HES resulted in better preservation of cardiac function, which was demonstrated by maintenance of systolic function and oxygenation parameters. Minor loss of cellular integrity with HES, in the presence of very low levels of hemoglobin, reinforces these findings.

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