Abstract

ERYTHROCYTE-ASSOCIATED TRANSIENTS IN CAPILLARY PO2 IN THE RAT SPINOTRAPEZIUS MUSCLE DURING HEMODILUTION WITH HESPAN AND A HEMOGLOBIN-BASED OXYGEN CARRIER By Matthew C. Barker A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University Virginia Commonwealth University, 2005 Advisor: Roland N. Pittman, Ph.D. Department of Physiology Hemoglobin-based oxygen carriers for use as transfusion fluids have emerged as a leading technology directed at stemming shortages of a safe blood supply and providing a readily available resuscitation fluid in various trauma situations. The purpose of this investigation was to determine the effects of isovolemic hernodilution with Hespan and a hemoglobin-based oxygen carrier (HBOC) on erythrocyte-associated transients (EATs) in capillary PO2. The particulate nature of blood flow in capillaries, when observed from a stationary observation point, results in fluctuations of PO2 as alternating red blood cells and plasma gaps move through the detection region. Therefore, through experimental methods which provided the necessary temporal and spatial resolution required to make such measurements, EATs can be observed and corresponding PO2 fluctuations can be determined. The spinotrapezius muscle in sixteen Sprague-Dawley rats was exteriorized for intravital microscopy measurements in capillaries. Capillary PO2 was measured using Pd-porphyrin phosphorescence quenching microcopy. The hemodiluents used in isovolemic hemodilution included Hespan, a non-oxygen carrying plasma expander, and OxyglobinB, a HBOC. Two isovolemic hemodilution steps were performed, reducing the systemic hematocrit to an average of 27.5% after the first step and 13.5% after the second step. Results showed that erythrocyte-associated transients in PO2 can be observed in the rat spinotrapezius with significant differences occurring between red blood cell and plasma gap PO2 under control conditions, isovolemic hemodilution with Oxyglobin after step one, and isovolemic hemodilution with Hespan after step two. This study concludes that EATs are observable and POz transients relating to EATs can be measured in the rat spinotrapezius muscle. Furthermore, it can be concluded that the HBOC Oxyglobin caused a decrease in erythrocyte-associated capillary POz transients, as well as a general decrease in capillary PO2. In addition, this study concludes that erythrocyte-associated capillary PO2 transients can best be observed under control conditions and after step two of isovolemic hemodilution with Hespan.

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