Analysis of intracellular oxygenation of isolated adult cardiac myocytes

Abstract

The influence of cellular shape, cellular O2 consumption rate, and intracellular diffusion coefficient for O2 on the magnitude of intracellular O2 gradients during hypoxia was analyzed with the model of Boag (Curr. Top. Radiat. Res. 5: 141-195, 1969) to determine whether these parameters could account for the experimentally measured O2 dependence curves for myoglobin (Mb) oxygenation and cytochrome a + a3 oxidation in heart cells. The analysis shows that the intracellular diffusion coefficient for O2 must be below 4 X 10(-6) cm2/s for a substantial intracellular gradient to occur. The intracellular diffusion coefficient was calculated from the difference in half-maximal oxidation (P50) values for isolated Mb and intracellular Mb and was found to be 1.76 X 10(-6) cm2/s. Use of this value and appropriate geometric models satisfactorily described the O2 dependence of Mb oxygenation and cytochrome a + a3 oxidation in cells over an eightfold range of O2 consumption rates. However, the analysis does not account for the correspondence of intracellular P50 values of Mb oxygenation and cytochrome a + a3 oxidation. This implies that there exists an intracellular heterogeneity of either Mb distribution, mitochondrial distribution, or mitochondrial respiratory characteristics. Such heterogeneity would further contribute to diffusion limitation of O2 supply during hypoxia and could be a major factor underlying the cardiac myocyte structure-function relationship.