Myocardial aerobic metabolism is impaired in a cell culture model
of cyanotic heart disease.
Merante, Frank, Donald A. G. Mickle, Richard D. Weisel, Ren-Ke Li,
Laura C. Tumiati, Vivek Rao, William G. Williams, and Brian H.
Robinson.
Centre for Cardiovascular Research, The Toronto Hospital and the
University of Toronto. Toronto, Ontario. Canada
APStracts 5:0296H, 1998.
A human pediatric cardiomyocyte cell culture model of chronic cyanosis
was used to assess the effects of low oxygen tension on mitochondrial
enzyme activity to address the post-operative increase in lactate and
decreased ATP in the myocardium and the high incidence of low output
failure with restoration of normal oxygen tension, after technically
successful corrective cardiac surgery. Chronically hypoxic cells
(pO2=40 mm Hg for 7 days) exhibited significantly reduced activities
for: pyruvate dehydrogenase, cytochrome c oxidase, succinate
cytochrome c reductase, succinate dehydrogenase and citrate synthase.
The activity of NADH-cytochrome c reductase was unaffected. Lactate
production and the lactate to pyruvate ratio were significantly
greater in hypoxic cardiomyocytes. Western and Northern analysis
demonstrated a decrease in the levels of various mRNAs and
corresponding polypeptides in hypoxic cells. Thus, hypoxia influences
mitochondrial metabolism through acute and chronic adaptive
mechanisms, reflecting allosteric (post-transcriptional) and
transcriptional modulation. Transcriptional down-regulation of key
mitochondial enzyme systems can expain the insufficient myocardial
aerobic metabolism and low output failure in children with cyanotic
heart disease after cardiac surgery.
Received 19 September 1997; accepted in final form 20 July 1998.
APS Manuscript Number H875-7.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998