Regulation of oxygen diffusion in hypoxic isolated cardiac
myocytes.
Takahashi, Eiji, and Katsuhiko Doi.
Affiliation: Department of Physiology, Yamagata University School
of Medicine, Yamagata 990-23, Japan
APStracts 3:0196H, 1996.
In the normal beating heart, oxygen pressure (Po2) gradients between
capillary blood and intracellular space are so large that cytosolic
Po2 may decline to around P50 of myoglobin (25 Torr). Hence, a
decrease in capillary blood Po2 of a few Torr would easily deplete
oxygen in mitochondria, if Po2 gradients are unchanged. The aim of
the present study was to demonstrate, in a single isolated cardiac
myocyte of the rat, a mechanism that reduces Po2 gradients in
hypoxia, so that oxygenation of the intracellular space would be
sustained. Using a newly developed microspectrophotometric device, we
were able to follow changes in cytosolic Po2 of an individual
ventricular myocyte in a hypoxic medium. For extracellular Po2 of 4.4
Torr, we found an elevation (2.1 Torr) of the cytosolic Po2 when
oxygen consumption of the cell was abolished by 2 mM NaCN, thus
demonstrating Po2 gradients from extracellular medium to cytosolic
space in a single individual cardiomyocyte. The magnitude of these
Po2 gradients was reduced as extracellular Po2 was further lowered,
and they were no longer detectable for extracellular Po2 of 0.6 Torr.
To further elucidate physiological effects of the Po2 dependent
changes in Po2 gradients demonstrated above, we conducted a
simulation of ischemia in a single cardiac myocyte. The stop flow
procedure (simulated ischemia) quickly decreased cytosolic Po2 from
7.3 Torr to 1.8 Torr in 5 min, while the rate of fall of Po2
considerably decreased when the cytosolic Po2 decreased to <2
Torr. Consequently, even 30 min after the onset of the stop flow,
cytosolic Po2 was significantly higher than that of the anoxic
perfusion. These results together suggest that in severe hypoxia
oxygenation of the intracellular space might be partially maintained
by relative elevation of cytosolic Po2 resulting from progressive
decrease in Po2 gradients from extracellular space to cytosol.
Received 22 February 1996; accepted in final form 24 September
1996.
APS Manuscript Number H178-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96