Effect of gradual reduction in o2 delivery on intracellular
homeostasis in contracting skeletal muscle.
Hogan, Michael C., S. Sadi Kurdak, Peter G. Arthur.
Division of Physiology, Department of Medicine, University of
California, San Diego, La Jolla, CA 92093-0623 and Department of
Biochemistry, University of Western Australia, Nedlands, Western
Australia 6009
APStracts 2:0491A, 1995.
This study was designed to investigate: 1) whether a protocol
employing a gradual reduction in O2 availability to submaximally
contracting muscle results in relatively minor disturbances in
intracellular homeostasis; and 2) the interaction between tissue
oxygenation and the proposed regulators of muscle respiration,
metabolism, and force production. O2 delivery to isolated,
submaximally contracting (isometric contractions at 3 Hz; about 50%
of peak oxygen uptake) in situ canine gastrocnemius (n=6) was
manipulated by either decreasing arterial PO2 (hypoxemia; H) or
muscle blood flow (ischemia; I) during 3 separate periods in each
muscle (control, H, or I; each separated by 45 min rest). O2 delivery
was reduced gradually in small steps every 3 min by either H or I
during 2 of the contraction periods (6 steps for a total of 21 min;
O2 delivery reduced by 67% by the end of 21 min), while the control
condition (C) was at normal O2 delivery for a 15-min period. Muscle
oxygen uptake (VO2) was maintained at control levels for the first
two O2 delivery reduction steps for both the H and I conditions, and
then fell proportionally with O2 delivery to approximately 35% of the
initial value by the end of the 21-min contraction period. Muscle
force development generally fell in parallel with VO2. There were no
significant changes from the values obtained during control period
contractions in intracellular concentrations of ATP, PCr, NH3,
calculated free ADP, lactate, and redox state ratios as the O2
delivery was reduced, even with the severe decline in VO2 and
developed force. These results demonstrated that when O2 availabilty
was reduced gradually to contracting skeletal muscle: 1) developed
force (ATP utilization) was reduced through a tight coupling with
aerobic ATP supply such that there was little additional disruption
of intracellular homeostasis; and 2) there was an apparent
dissociation of some of the proposed regulators of cell respiration
and force development from the control of these processes.
Received 26 June 1995; accepted in final form 1 November 1995.
APS Manuscript Number A681-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95