Physical exercise tolerance declines with advancing age and chronic diseases (e.g., chronic heart failure (CHF)) prevalent in the aging community. The degree to which structural and functional alterations within skeletal muscle participate in this effect is unclear. However, there is strong evidence that some facet of the aging process impairs muscle blood flow and its microvascular distribution. This will impair effective oxygen (O2) and substrate delivery and the removal of metabolites. We propose to utilize a unique combination of established (microspheres, intravital microscopy) and novel (phosphorescence quenching measurement of micro vascular partial pressure of O2 (PO2)) methodologies to explore the effects of aging and chronic disease on muscle structure, blood flow and its microvascular distribution and the process of O2 exchange within the microcirculation. Using the rat model of aging and chronic heart failure (CHF), we will test the following hypotheses: 1) Aging reduces perfusion in key limb muscles during both sub maximal and maximal exercise but not at rest. 2) At rest and during sub maximal and maximal muscle contractions, muscle capillary red blood cell (RBC) distribution and velocities become more heterogeneous and this impairs the matching of O2 requirements to O2 delivery (VO2-to-QO2) such that muscle O2 extraction is impaired. 3) The kinetics of muscle O2 exchanges are slowed in aged and diseased muscle and this is associated with increased heterogeneity of capillary RBC distribution and dynamics. These studies will demonstrate the feasibility and validity of obtaining key information at the integrated and isolated muscle level in young and old rats with and without CHF and provide essential mechanistic insights into the role of skeletal muscle vascular dysfunction in the exercise intolerance of the elderly and chronic disease patient populations.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG019228-02
Application #
6509965
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Premen, Andre J
Project Start
2001-04-01
Project End
2005-03-31
Budget Start
2002-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2002
Total Cost
$218,250
Indirect Cost
Name
Kansas State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Manhattan
State
KS
Country
United States
Zip Code
66506
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Poole, David C; Hirai, Daniel M; Copp, Steven W et al. (2012) Muscle oxygen transport and utilization in heart failure: implications for exercise (in)tolerance. Am J Physiol Heart Circ Physiol 302:H1050-63
Poole, D C; Copp, S W; Hirai, D M et al. (2011) Dynamics of muscle microcirculatory and blood-myocyte O(2) flux during contractions. Acta Physiol (Oxf) 202:293-310
Copp, Steven W; Hageman, K Sue; Behnke, Brad J et al. (2010) Effects of type II diabetes on exercising skeletal muscle blood flow in the rat. J Appl Physiol 109:1347-53
Behnke, Bradley J; Delp, Michael D; Poole, David C et al. (2007) Aging potentiates the effect of congestive heart failure on muscle microvascular oxygenation. J Appl Physiol 103:1757-63
Poole, David C; Ferreira, Leonardo F (2007) Oxygen exchange in muscle of young and old rats: muscle-vascular-pulmonary coupling. Exp Physiol 92:341-6
Padilla, Danielle J; McDonough, Paul; Behnke, Brad J et al. (2007) Effects of Type II diabetes on muscle microvascular oxygen pressures. Respir Physiol Neurobiol 156:187-95
Hahn, S A; Ferreira, L F; Williams, J B et al. (2007) Downhill treadmill running trains the rat spinotrapezius muscle. J Appl Physiol 102:412-6
McDonough, Paul; Behnke, Brad J; Padilla, Danielle J et al. (2007) Control of microvascular oxygen pressures during recovery in rat fast-twitch muscle of differing oxidative capacity. Exp Physiol 92:731-8

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