Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2008 Effect of Hemoglobin-Based Oxygen Carriers on Arterial Pressure and Vasoactivity in the Rat Mesentery Michael Kim Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Physiology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/1675 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. EFFECT OF HEMOGLOBIN-BASED OXYGEN CARRIERS ON ARTERIAL PRESSURE AND VASOACTIVITY IN THE RAT MESENTERY A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at the Medical College of Virginia Campus, Virginia Commonwealth University by MICHAEL Y KIM B.A. Biology, University of Virginia 2006 Advisor Roland N. Pittman, Ph.D. Professor Department of Physiology and Biophysics Virginia Commonwealth University Richmond, Virginia May 2008 ii Table of Contents List of Tables .................................................................................................................... vii List of Tables .................................................................................................................... vii Abstract............................................................................................................................ viii Introduction......................................................................................................................... 1 The Cardiovascular System ............................................................................................ 1 Circulation................................................................................................................... 1 Blood Composition..................................................................................................... 2 Oxygen............................................................................................................................ 2 Cellular Requirements for Oxygen ............................................................................. 2 Oxygen Transport ....................................................................................................... 3 Hemoglobin................................................................................................................. 4 Nitric Oxide ....................................................................................................................5 Physiological Effects .................................................................................................. 5 Vasoactivity ................................................................................................................ 6 Nitric Oxide Synthase................................................................................................. 6 Hemoglobin Based Oxygen Carriers .............................................................................. 7 History.........................................................................................................................7 Side Effects of HBOC................................................................................................. 8 Alternatives to HBOCs ............................................................................................. 10 Modification of HBOCs............................................................................................ 10 Purpose of the Study..................................................................................................... 11 Methods and Materials...................................................................................................... 12 iii Animal Preparation:...................................................................................................... 12 Surgical Procedures: ..................................................................................................... 13 Mesentery Preparation .................................................................................................. 14 Properties and Preparation of HBOC’s......................................................................... 14 HBOC 201 Infusions................................................................................................. 15 HBOC 205 (MW 400) .............................................................................................. 15 HBOC 205 (MW 600) .............................................................................................. 16 Solutions Prepared ........................................................................................................ 16 Normal Saline ........................................................................................................... 16 Hepranized Saline ..................................................................................................... 16 Sodium Nitrite........................................................................................................... 17 L-NAME................................................................................................................... 17 Imaging Microscope and Software............................................................................... 17 Data Acquisition ........................................................................................................... 18 Measurement of Mean Arterial Pressure .................................................................. 18 Measurement of Arteriolar Diameter........................................................................ 19 Experimental Protocol .................................................................................................. 19 Human Serum Albumin ............................................................................................ 19 HBOC ....................................................................................................................... 19 Sodium Nitrite Controls............................................................................................ 20 NaNO2 and HBOC Time Controls............................................................................ 21 HBOC and NaNO2 .................................................................................................... 21 Simultaneous HBOC and NaNO2 ............................................................................. 21 iv L-NAME................................................................................................................... 22 Results............................................................................................................................... 24 HBOC ........................................................................................................................... 24 HSA........................................................................................................................... 24 Dose Dependent Effects HBOC 201......................................................................... 24 Dose Dependent Effects of HBOC 205 (MW 400) .................................................. 25 Dose Dependent Effects of HBOC 205 (MW 600) .................................................. 25 Sodium Nitrite............................................................................................................... 26 NaNO2 Control.......................................................................................................... 26 NaNO2 Time Control ................................................................................................ 26 HBOC 201 Time Control.......................................................................................... 26 NaNO2 Dose Response Effects following Single HBOC 201 Dose......................... 27 Simultaneous NaNO2 and HBOC effects ................................................................. 27 L-Name and NaNO2 Dose Response Effects............................................................ 28 Discussion......................................................................................................................... 69 HBOC ........................................................................................................................... 69 Dose-Dependent Effects of the HBOCs ................................................................... 69 Comparison to Previous Literature ........................................................................... 69 Sodium Nitrite............................................................................................................... 72 Dose Dependent Effects of the NaNO2 following a HBOC 201 Dose..................... 72 L-NAME and NaNO2 Effects ................................................................................... 73 Comparisons to Previous Literature.......................................................................... 74 Further Studies.......................................................................................................... 76 v Conclusion ................................................................................................................ 76 Bibliography ....................................................................................................................