Impaired Tissue Oxygenation in Metabolic Syndrome Requires Increased Microvascular Perfusion Heterogeneity.
Metabolic syndrome (MS) in obese Zucker rats (OZR) is associated with impaired skeletal muscle performance and blunted hyperemia. Studies suggest that reduced O2diffusion capacity is required to explain compromised muscle performance and that heterogeneous microvascular perfusion distribution is critical. We modeled tissue oxygenation during muscle contraction in control and OZR skeletal muscle using physiologically realistic relationships. Using a network model of Krogh cylinders with increasing perfusion asymmetry and increased plasma skimming, we predict increased perfusion heterogeneity and decreased muscle oxygenation in OZR, with partial recovery following therapy. Notably, increasing O2delivery had less impact on VO2than equivalent decreases in O2delivery, providing a mechanism for previous empirical work associating perfusion heterogeneity and impaired O2extraction. We demonstrate that increased skeletal muscle perfusion asymmetry is a defining characteristic of MS and must be considered to effectively model and understand blood-tissue O2exchange in this model of human disease.
Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.|Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.|Department of Medicine, Denver Veterans Affairs Medical Center, Denver, CO, USA.
P
P
Mason McClatchey
Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
Fan
F
Wu
Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, WV, USA.
I Mark
IM
Olfert
Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, Medical Sciences Building, M407, 1151 Richmond Street North, London, ON, N6A 5C1, Canada.
Christopher G
CG
Ellis
Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, Medical Sciences Building, M407, 1151 Richmond Street North, London, ON, N6A 5C1, Canada.
Daniel
D
Goldman
Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.|Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
Jane E B
JEB
Reusch
Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, Medical Sciences Building, M407, 1151 Richmond Street North, London, ON, N6A 5C1, Canada. jfrisbee@uwo.ca.
Jefferson C
JC
Frisbee
D000818:Animals; D001783:Blood Flow Velocity; D015687:Cell Hypoxia; D003198:Computer Simulation; D004195:Disease Models, Animal; D007700:Kinetics; D024821:Metabolic Syndrome / Q000097:blood / Q000503:physiopathology*; D008833:Microcirculation; D055806:Microvessels / Q000503:physiopathology*; D008955:Models, Cardiovascular; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D011924:Rats, Zucker; D012039:Regional Blood Flow
D010100:Oxygen
Blood flow control; Microcirculation; Oxygenation; Rodent models of obesity; Simulation