Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)


Medical Sciences




The possibility that a lowered hemoglobin-oxygen affinity (+P₅₀) of coronary arterial blood may enhance ischemic myocardial tissue oxygenation and hence cardiac function was examined. Incubation techniques were developed whereby canine intraerythrocytic 2,3-diphosphoglycerate (2,3-DPG) and P₅₀ were significantly increased. Whereas the purine nucleoside adenosine was ineffective in increasing red cell 2,3-DPG, the triose compound dihydroxyacetone (DHA) significantly increased 2,3-DPG (6.3±0.2 - 12.7±0.6 mM/L.RBC) and P₅₀ (27.7±0.5 - 36.3±1.1mm Hg). Both pyruvate and inorganic phosphate were necessary components of the incubation medium in order to observe the above effects of DHA. Using the canine model, a surgical technique was developed which permitted acute, controlled reductions in total left ventricular myocardial blood flow. Acute myocardial ischemia had no significant effect on coronary sinus blood P₅₀ or 2,3-DPG content. Coronary cross perfusion from a secondary coronary arterial supply circuit containing blood with an increased P₅₀ under control and ischemic flow conditions demonstrated that the coronary vasomotor status is influenced by the hemoglobin-oxygen affinity. Coronary cross perfusion resulted in a reversible decline in cardiac contractile performance and oxygen utilization. Cross perfusion with high 2,3-DPG blood resulted in less of a decline in these two parameters. In contrast to acute myocardial ischemia, chronic myocardial ischemia and infarction produced statistically significant increases in systemic venous hemoglobin-oxygen dissociation kinetics and, to a lesser degree, P₅₀ and 2,3-DPG.

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