Effects of Hemoglobin-Based Oxygen Carriers on the Vasoactivity of the Spinotrapezius Muscle of the Rat

Abstract

EFFECTS OF HEMOGLOBIN-BASED OXYGEN CARRIERS ON VASOACTIVITY IN THE SPINOTRAPEZIUS MUSCLE OF THE RAT By Pete Dennis Meliagros A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University Virginia Commonwealth University, 2008 Advisor: Roland N. Pittman, Ph.D. Department of Physiology and Biophysics Hemoglobin-based oxygen carriers (HBOCs) offer a safe, more plentiful and long term alternate to blood banks. However, they have been found to increase blood pressure which can be attributed to an increase in total peripheral resistance (TPR). Lumenal nitric oxide (NO) scavenging by these HBOCs seems to be responsible for this hypertensive effect. In addition, it is believed that hemoglobin (Hb) tetramers and dimers may extravasate and consume additional nitric oxide in the perivascular and interstitial space. The purpose of the present study was to elucidate the role of NO scavenging and to confirm extravasation as a contributor to HBOC vasopressor effects in the spinotrapezius muscle. The present study investigated the vessel reactivity and mean arterial pressure response to three HBOCs: HBOC 201, HBOC 205 MW 400, and HBOC 205 MW 600. These varied in molecular weight (MW) and percentage of tetramers and dimers. It was found that larger polymers of HBOC showed no significant decrease in vasoactivity. Although larger polymers are less likely to extravasate, the remaining tetramers and dimers seem sufficient to contribute to the observed vasoactivity. Using NaNO2, a NO donor, in conjunction with the HBOCs almost completely abolished this