The goal of this project is to evaluate the compensatory alterations in oxygen transport which occur at the microcirculatory level in striated muscle following changes in oxygen delivery induced by increasing or decreasing the affinity of the red blood cell hemoglobin for oxygen. Experiments will be performed on the cheek pouch retractor muscle of the golden hamster. Oxygen affinity will be determined by the position of the oxyhemoglobin dissociation curve assessed by determining a standard P50 (oxygen tension (P02) at which red blood cell hemoglobin is 50% saturated at pH 7.4, Base Excess = 0, 37 degrees C). Changes in oxygen affinity will be accomplished by either the chronic, short term administration of sodium cyanate (left-shift) or ortho-iodosodium benzoate (right-shift) or acute exchange transfusion with donor red blood cells which have been treated in vitro with sodium cyanate (left-shift) or inositol hexaphosphate (right-shift). The impact of alterations in oxygen affinity will be assessed by evaluating geometric (luminal diameter; capillary density), hemodynamic (red blood cell velocity; large vessel hemoglobin concentration; capillary lineal density), oxygenation (oxygen saturation (S02)) and oxygen exchange (longitudinal S02 gradient) parameters in both large (arterioles and venules) and small (capillaries) microvessels. The data on the large vessels will be analyzed on-line while that for the capillaries will be analyzed off-line from video tapes using state-of-the-art methodologies. The data obtained from animals with altered oxygen affinity will be compared with similar data obtained from appropriate age-matched, sham-treated control animals. The initial studies will be undertaken under normoxic, resting conditions. We will subsequently assess the impact of alterations of oxygen affinity on muscle oxygenation in the presence of an altered oxygen supply (altered inspired P02), increased oxygen demand (muscle contraction) and a combination of a decreased oxygen supply with an increased oxygen demand. These studies will provide valuable information on the importance of oxygen affinity for the adequate supply of oxygen to striated muscle and insights into its importance in other tissues for which the appropriate supply of oxygen is crucial to the animal's survival. In addition, these studies should provide useful information on the relationship between the coincident clinical observations of an impairment of peripheral oxygen utilization and altered hemoglobin oxygen affinity.
