Myocardial oxygenation and high-energy phosphate levels during graded coronary hypoperfusion

This study was performed to determine the myocyte Po₂ required to sustain normal high-energy phosphate (HEP) levels in the in vivo heart. In 10 normal dogs, myocyte Po₂ values were calculated from the myocardial deoxymyoglobin resonance [Mb-δ) intensity determined with ¹H-NMR spectroscopy during sequential flow reductions produced by a hydraulic occluder that decreased coronary perfusion pressure to ∼60, 50, and 40 mmHg and, finally, during total occlusion. Myocardial blood flow was measured with microspheres, and HEP levels were determined with ³¹P magnetic resonance spectroscopy. During control conditions, Mb-δ was undetectable. Myocardial blood flow was 1.11 ± 0.06 ml·min ¹·g ¹ during basal conditions and decreased with sequential graded occlusions to 0.78 ± 0.05, 0.58 ± 0.03, and 0.38 ± 0.04 ml·min ¹·g ¹, respectively; blood flow during total occlusion was 0.07 ± 0.02 ml·min ¹·g^-1. Reductions of blood flow caused progressive increases of Mb-δ, which were associated with decreases of phosphocreatine (PCr), ATP, and the PCr-to-ATP ratio, as well as progressive ir creases of the P_i-to-PCr ratio. There was a strong linear correlation between normalized blood flow and Mb-δ (R² = 0.89, P < 0.01). Reductions of HEP and Po₂ were also highly correlated (although nonlinearly); with the assumption that myoglobin was 90% saturated with O₂ during basal conditions and 5% salurated during total coronary occlusion, the intracellular Po₂ values for 20% reductions of PCr and ATP were ∼4.4 and ∼0.9 mmHg, respectively. The data indicate that O₂ availabiliy plays an increasing role in regulation of oxidative phosphorylation when mean intracellular Po₂ values fall below 5 mmHg in the in vive heart.