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Model of oxygen transport and metabolism predicts effect of hyperoxia on canine muscle oxygen uptake dynamics

Departments of ¹Biomedical Engineering and ²Pediatrics and ³Center for Modeling Integrated Metabolic Systems, Case Western Reserve University and ⁴Rainbow Babies and Children's Hospital, Cleveland, Ohio; ⁵Dipartimento di Scienze e Tecnologie Biomediche, Universita’ degli Studi di Milano, Italy; and ⁶Department of Kinesiology, Auburn University, Alabama

Submitted 4 May 2007 ; accepted in final form 27 June 2007

Previous studies have shown that increased oxygen delivery, via increased convection or arterial oxygen content, does not speed the dynamics of oxygen uptake, O_2m, in dog muscle electrically stimulated at a submaximal metabolic rate. 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 O_2m dynamics at contraction onset, we combined dynamic experimental data across working muscle with a mechanistic model of oxygen transport and metabolism in muscle. 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 gastrocnemius muscle. Simulations of arteriovenous O₂ differences and O_2m dynamics were successfully compared with experimental data (Grassi B, Gladden LB, Samaja M, Stary CM, Hogan MC. J Appl Physiol 85: 1394–1403, 1998; and Grassi B, Gladden LB, Stary CM, Wagner PD, Hogan MC. J Appl Physiol 85: 1404–1412, 1998), thus demonstrating the validity of the model, as well as its predictive capability. The main findings of this study are: 1) the estimated dynamic response of oxygen utilization at contraction onset in muscle is faster than that of oxygen uptake; and 2) 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. These in silico derived results cannot be obtained from experimental observations alone.

This article has been cited by other articles:

				N. Lai, H. Zhou, G. M. Saidel, M. Wolf, K. McCully, L. B. Gladden, and M. E. Cabrera Modeling oxygenation in venous blood and skeletal muscle in response to exercise using near-infrared spectroscopy J Appl Physiol, June 1, 2009; 106(6): 1858 - 1874. [Abstract] [Full Text] [PDF]