Myoglobin function evaluated in working heart tissue

Abstract

Previous modeling efforts suggest that myoglobin-facilitated diffusion contributes very little to oxygen transport in a Krebs-Henseleit perfused isolated heart when literature-derived values for the diffusion coefficient of myoglobin (D(Mb)) were used. Simulations have strongly suggested that the contractile mechanisms of muscle may augment diffusion in working preparations. Myoglobin-facilitated oxygen diffusion may be augmented by the same mechanism. In this study, parameters of an oxygen transport to tissue model are optimized to investigate the possibility of elevated diffusion coefficients for oxygen and myoglobin in working heart tissue. The Radially- Averaged, Axially-Distributed (RAAD) model considers axial diffusion of oxygen in tissue, myoglobin facilitation of oxygen transport, and pO2- dependent oxygen consumption (Michaelis-Menten kinetics). Models are solved numerically using a variable-mesh finite-difference scheme. Parameters are optimized using a Nelder-Mead simplex routine and are chosen to minimize the sum-of-squares error (SSE) between model oxygen partial pressure (pO2) predictions and experimental pO2 data. Models are solved both with and without myoglobin facilitation. Myoglobin was found to have little effect on the oxygen distribution predicted by the models. Optimized values for the oxygen diffusion coefficient remained elevated. However, optimized values for myoglobin diffusion coefficient were found to be less than measured values. The RAAD model optimization results suggest that myoglobin does not significantly facilitate oxygen diffusion to tissue in the steady state and that myoglobin diffusion is not elevated in working heart.