Regulation of oxygen diffusion in hypoxic isolated cardiac myocytes

In the normal beating heart, oxygen pressure (PO2) gradients between capillary blood and intracellular space are so large that cytosolic PO2 may decline to around PO2 at half saturation of myoglobin (2-5 Torr). Hence, a decrease in capillary blood PO2 of a few Torr would easily deplete oxygen in mitochondria if PO2 gradients are unchanged. The aim of the present study was to demonstrate, in a single isolated cardiac myocyte of the rat, a mechanism that reduces PO2 gradients in hypoxia so that oxygenation of the intracellular space would be sustained. Using a newly developed microspectrophotometric device, we were able to follow changes in cytosolic PO2 of an individual ventricular myocyte in an hypoxic medium. For extracellular PO2 of 4.4 Torr, we found an elevation (2.1 Torr) of the cytosolic PO2 when oxygen consumption of the cell was abolished by 2 mM NaCN, thus demonstrating PO2 gradients from extracellular medium to cytosolic space in a single individual cardiomyocyte. The magnitude of these PO2 gradients was reduced as extracellular PO2 was further lowered, and they were no longer detectable for extracellular PO2 of 0.6 Torr. To further elucidate physiological effects of the PO2-dependent changes in PO2 gradients demonstrated above, we conducted a simulation of ischemia in a single cardiac myocyte. The stop-flow procedure (simulated ischemia) quickly decreased cytosolic PO2 from 7.3 to 1.8 Torr in 5 min, while the rate of fall of PO2 considerably decreased when the cytosolic PO2 decreased to < 2 Torr. Consequently, even 30 min after the onset of the stop flow, cytosolic PO2 was significantly higher than that of the anoxic perfusion. These results together suggest that in severe hypoxia oxygenation of the intracellular space might be partially maintained by relative elevation of cytosolic PO2, resulting from progressive decrease in PO2 gradients from extracellular space to cytosol.