• Lindstedt, Stan L (PI)

Project: Research project

Grant Details


The mammalian respiratory system is not a single structure but
rather a series of linked structures, each contributing to the
overall resistance (or finite capacity) for oxygen transport. Some
of the structural resistors in the cascade have considerable
phenotypic plasticity and hence are acutely adaptable to the level
of 02 flow. Others of the structural resistors are nearly lacking
phenotypic plasticity; these must be designed (and maintained) at
a level that will satisfy peak potential species-specific demands.
The first aim of this study is to quantify the relationship between
02 demand and 02 supply through the respiratory system. Which of
the structural resistors is (are) overbuilt and which acts to limit
02 flow? The second aim of this study is to quantify two of the
upstream resistors and measure their structural and functional
responses to induced increases in 02 demand via long-term endurance
training. We propose to quantify pulmonary diffusing capacity and
cardiovascular 02 delivery in response to long-term endurance
training. The final aim of this study is to couple an examination
of muscle biochemistry and ultrastructure to "whole animal" 02
demand and quantify these properties during and following endurance
training. These goals will be accomplished experimentally by
coupling a long-term endurance training study (in domestic goats)
with final experiments in which the fractional content of inspired
02 and hemoglobin concentration will be simultaneously manipulated.
Untrained sibling pairs will act as controls during the study. The
resultant physiological data will be coupled with measurements of
pulmonary diffusing capacity, lung function tests, muscle
ultrastructure, and muscle biochemistry. While this study is not
proposed as the definitive study, it should provide some missing
information because it utilizes at least two uncommon approaches.
First, we will examine multiple (though not all) transport steps
simultaneously. Second, we will couple biochemical, anatomical and
physiological data from the same animals. Finally, we propose to
examine these structures and functions during the course of long-
term endurance training. These are the strengths of the study:
a coupling of physiological and biochemical data and an
experimental (vs. descriptive only) approach to examine the design
consequences of endurance training.
Effective start/end date7/1/896/30/93


  • National Institutes of Health


  • Medicine(all)


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