Article

Annals of Biomedical Engineering

, Volume 35, Issue 6, pp 956-969

First online:

Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise

  • Nicola LaiAffiliated withBiomedical Engineering, Case Western Reserve UniversityDepartment of Pediatrics, Case Western Reserve UniversityCenter for Modeling Integrated Metabolic Systems, Case Western Reserve University
  • , Marco CamesascaAffiliated withDepartment of Pediatrics, Case Western Reserve UniversityRainbow Babies and Children’s Hospital
  • , Gerald M. SaidelAffiliated withBiomedical Engineering, Case Western Reserve UniversityCenter for Modeling Integrated Metabolic Systems, Case Western Reserve University
  • , Ranjan K. DashAffiliated withDepartment of Pediatrics, Case Western Reserve UniversityCenter for Modeling Integrated Metabolic Systems, Case Western Reserve University
  • , Marco E. CabreraAffiliated withBiomedical Engineering, Case Western Reserve UniversityDepartment of Pediatrics, Case Western Reserve UniversityCenter for Modeling Integrated Metabolic Systems, Case Western Reserve UniversityRainbow Babies and Children’s HospitalPediatric Cardiology, MS-6011, Case Western Reserve University Email author 

Abstract

The energy demand imposed by physical exercise on the components of the oxygen transport and utilization system requires a close link between cellular and external respiration in order to maintain ATP homeostasis. Invasive and non-invasive experimental approaches have been used to elucidate mechanisms regulating the balance between oxygen supply and consumption during exercise. Such approaches suggest that the mechanism controlling the various subsystems coupling internal to external respiration are part of a highly redundant and hierarchical multi-scale system. In this work, we present a “systems biology” framework that integrates experimental and theoretical approaches able to provide simultaneously reliable information on the oxygen transport and utilization processes occurring at the various steps in the pathway of oxygen from air to mitochondria, particularly at the onset of exercise. This multi-disciplinary framework provides insights into the relationship between cellular oxygen consumption derived from measurements of muscle oxygenation during exercise and pulmonary oxygen uptake by indirect calorimetry. With a validated model, muscle oxygen dynamic responses is simulated and quantitatively related to cellular metabolism under a variety of conditions.

Keywords

Cellular metabolism Modeling Multi-scale approach Oxygen transport Oxidative phosphorylation Systems biology