Hemorrhagic shock can be an unfortunate sequela of severe trauma, surgery, and coagulopathy. Survival from hemorrhagic shock depends on restoration of tissue oxygenation and blood flow. Despite numerous experimental and clinical efforts, no clear benefit has been demonstrated for IV administration of one solution over another for resuscitation from hemorrhagic shock.
Hemoglobin-based oxygen carriers are modified purified hemoglobin solutions designed to restore oxygen-carrying capacity as well as to provide volume expansion in individuals with severe anemia or hemorrhage. Although effective at carrying oxygen, there are several limitations to the use of HBOCs, the most important of which is vasoconstriction secondary to scavenging of nitric oxide from the endothelial surface of blood vessels.1 This has been linked to development of hypertension and myocardial infarction, thereby limiting the use of these products.2,3 In rodents, it is known that HBOCs also cause a significant decrease in FCD, an assessment of regional perfusion that is highly correlated with tissue survival.1,4
A novel treatment strategy that has been explored in rodents as well as dogs with experimentally induced hemorrhagic shock is administration of viscosity-enhanced solutions.5–9 These solutions are created by adding an inert polymer that increases viscosity of the original solution without affecting oncotic pressure. During hemorrhage, decreased blood viscosity develops from loss of RBC mass as well as dilution of the blood through transcompartmental fluid shifting and administration of resuscitative fluid therapy. Decreased plasma viscosity leads to decreased endothelial surface shear stress and decreased endothelial nitric oxide production, subsequently resulting in vasoconstriction and maldistribution of blood flow.6,8,10 Resuscitation with hyperviscous solutions has been performed in rodents with hemorrhagic shock, and these solutions restored microcirculatory flow (through assessment of FCD) more effectively than did their standard counterparts.4,6,8,11
To best characterize the effects of HBOC administration and viscosity manipulation, direct visual assessment of the microcirculation is ideal. A videomicroscopea that incorporates sidestream dark-field technology can be used to image and assess microvascular perfusion. On the basis of previously established consensus criteria, the video recordings obtained during sidestream dark-field microscopy can be analyzed to determine several microcirculatory variables including total vessel density, perfused vessel density (a value analogous to FCD), proportion of perfused vessels, and microvascular flow index.12 This device has been used extensively in both experimental and clinical settings to document normal microvascular anatomy, and to evaluate changes induced by sepsis and hemorrhagic shock as well as a variety of other disease states.13–17
The purpose of the study reported here was to determine whether increasing the viscosity of a standard HBOC would offset its associated vasoconstrictive effects and result in improved microvascular perfusion in healthy splenectomized dogs with experimentally induced hemorrhagic shock. We hypothesized that administration of the hyperviscous HBOC would result in significantly improved tissue perfusion, compared with the effects of the standard HBOC, as determined by assessments of both macrovascular and microvascular variables.
Functional capillary density
Hemoglobin-based oxygen-carrying solution
Lactated Ringer's solution
Mean arterial blood pressure
Oxygen extraction ratio
Central venous oxygen saturation
Systemic vascular resistance index
Microscan, MicroVision Medical, Amsterdam, The Netherlands.
Oxyglobin, Biopure, Cambridge, Mass.
Datex, Instrumentarium Corp, Helsinki, Finland.
Passport 2, Datascope Corp, Fairfield, NJ.
LiDCO, LiDCO Ltd, London, England.
ABL 725, Radiometer America, Westlake, Ohio.
4420, Wescor, Logan, Utah.
DV-II+ viscometer, Brookfield Engineering Laboratories, Middleboro, Mass.
ADA Vascular Analysis, MicroVision Medical, Amsterdam, The Netherlands.
SigmaStat, version 3.5, Systat, San Jose, Calif.
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