Submitted on May 4, 2007
Accepted on June 27, 2007
Model of oxygen transport and metabolism predicts effect of hyperoxia on canine muscle oxygen uptake dynamics
Nicola Lai1, Gerald M Saidel2, Bruno Grassi3, L. Bruce Gladden4, and Marco E Cabrera5*
1 Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States
2 Biomedical Engineering, Case Western Reserve University, Cleveland , Ohio, United States
3 Scienze e Tecnologie Biomediche, Universita degli Studi di Milano, Milano, Lombardia, Italy
4 Kinesiology, Auburn University, Auburn, Alabama, United States
5 Pediatrics, Case Western Reserve University, Cleveland, Ohio, United States
* To whom correspondence should be addressed. E-mail: mec6{at}cwru.edu.
Previous studies have showed that increased oxygen delivery, via increased convection or arterial oxygen content, does not speed the dynamics of oxygen uptake (VO2m) in dog muscle electrically stimulated submaximally. However, the dynamics of transport and metabolic processes that occur within working muscle in situ is typically unavailable in this experimental setting. To investigate factors affecting VO2m dynamics at contraction onset, we combined dynamic experimental data across working muscle with a mechanistic model of oxygen transport and metabolism. The model is based on dynamic mass balances for O2, ATP, and PCr. Model equations account for changes in cellular ATPase, oxidative phosphorylation and creatine kinase fluxes in skeletal muscle during exercise, and cellular respiration depends on [ADP] and [O2]. Model simulations were conducted at different levels of arterial oxygen content and blood flow to quantify the effects of convection and diffusion of oxygen on the regulation of cellular respiration during step transitions from rest to isometric contraction in dog muscle. Simulations of arterio-venous O2 differences and VO2m dynamics were successfully compared with experimental data (Grassi et al., 1998a, b), thus demonstrating the validity of the model and its predictive capability. The main findings of this study are: (a) the estimated dynamic response of oxygen utilization at contraction onset in muscle is faster than that of oxygen uptake; and (b) hyperoxia does not accelerate the dynamics of diffusion and consequently muscle oxygen uptake at contraction onset due to the hyperoxia-induced increase in oxygen stores. Model results cannot be obtained from experimental observations alone.
