The long-term objective of this project is to demonstrate that hypervious fluids are efficacious in the treatment and improved survival from traumatic hemorrhagic shock. It is proposed to develop a treatment for hypovolemic cardiovascular collapse based on the infusion of high viscosity plasma expanders, which provide a novel small-volume resuscitation that recovers microvascular perfusion for extended periods until surgical control of bleeding is possible. The central hypothesis is that in conditions of hypotension, and cardiovascular collapse, high viscosity plasma restores moderate levels of mean arterial blood pressure needed to ensure open capillaries and tissue perfusion. Our data shows that open capillaries are critical to tissue survival, and viscogenic plasma expanders with tailored oncotic pressure properties restore microvascular function and rescue the organism from hypovolemic cardiovascular collapse. In the case of uncontrolled bleeding, these solutions provide limited-volume resuscitation with maximum microvascular perfusion and a gradual increase in blood pressure thereby minimizing re-bleeding, leading to important savings of blood transfusions, providing a new approach for dealing with conditions in which reduced tissue perfusion jeopardizes tissue survival in field conditions. In this project, a microcirculatory assessment in the hamster window preparation will be used with sophisticated and state of the art measurements of macro and microhemodynaimcs, including local pO2 levels, capillary pressure, and nitric oxide release. The properties of a transfusion fluid in terms of viscosity and oncotic properties which best recovers cardiovascular collapse will be identified in a lethal uncontrolled bleeding model.
| Sriram, Krishna; Salazar Vazquez, Beatriz Y; Tsai, Amy G et al. (2012) Autoregulation and mechanotransduction control the arteriolar response to small changes in hematocrit. Am J Physiol Heart Circ Physiol 303:H1096-106 |
| Cabrales, Pedro; Rameez, Shahid; Palmer, Andre F (2012) Hemoglobin encapsulated poly(ethylene glycol) surface conjugated vesicles attenuate vasoactivity of cell-free hemoglobin. Curr Drug Discov Technol 9:224-34 |
| Salazar Vázquez, Beatriz Y; Cabrales, Pedro; Tsai, Amy G et al. (2011) Nonlinear cardiovascular regulation consequent to changes in blood viscosity. Clin Hemorheol Microcirc 49:29-36 |
| Hightower, C Makena; Salazar Vázquez, Beatriz Y; Woo Park, Sung et al. (2011) Integration of cardiovascular regulation by the blood/endothelium cell-free layer. Wiley Interdiscip Rev Syst Biol Med 3:458-70 |
| Sriram, Krishna; Vazquez, Beatriz Y Salazar; Yalcin, Ozlem et al. (2011) The effect of small changes in hematocrit on nitric oxide transport in arterioles. Antioxid Redox Signal 14:175-85 |
| Palmer, Andre F; Zhang, Ning; Zhou, Yipin et al. (2011) Small-volume resuscitation from hemorrhagic shock using high-molecular-weight tense-state polymerized hemoglobins. J Trauma 71:798-807 |
| Tsai, Amy G; Cabrales, Pedro; Intaglietta, Marcos (2010) The physics of oxygen delivery: facts and controversies. Antioxid Redox Signal 12:683-91 |
| Cabrales, Pedro; Zhou, Yipin; Harris, David R et al. (2010) Tissue oxygenation after exchange transfusion with ultrahigh-molecular-weight tense- and relaxed-state polymerized bovine hemoglobins. Am J Physiol Heart Circ Physiol 298:H1062-71 |
| Cabrales, Pedro (2010) Low oxygen-affinity hemoglobin solution increases oxygenation of partially ischemic tissue during acute anemia. J Am Coll Surg 210:271-9 |
| Vazquez, Beatriz Y Salazar; Martini, Judith; Tsai, Amy G et al. (2010) The variability of blood pressure due to small changes of hematocrit. Am J Physiol Heart Circ Physiol 299:H863-7 |
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