Reperfusion injury in cardiac myocytes after simulated
ischemia.
Vandenhoek, Terry L., Zuohui Shao, Changqing Li, Radovan Zak, Paul T.
Schumacker, and Lance B. Becker.
Sections of Emergency Medicine, Cardiology, Pulmonary and Critical
Care Medicine, Department of Medicine, The University of Chicago,
Chicago, Illinois 60637
APStracts 2:0420H, 1995.
The extent of cardiac injury incurred during reperfusion as opposed to
that occurring during ischemia is unclear. This study tested the
hypothesis that simulated ischemia followed by simulated reperfusion
causes significant "reperfusion injury" in isolated chick
cardiomyocytes. Cells were exposed to hypoxia, hypercarbic acidosis,
hyperkalemia, and substrate deprivation for 1 hr followed by 3 hr
reperfusion. Irreversible cell membrane injury, measured by propidium
iodide uptake, increased from 4% of cells at the end of ischemia to
73% after reperfusion; cells kept ischemic for 4 hr had only 17%
death. LDH release was consistent with these changes. Lengthening
ischemia from 30 to 90 min increased cell injury as expected, but of
the total cell death, >90% occurred during reperfusion.
"Chemical hypoxia" comprised of cyanide (2.5mM) plus 2
-deoxyglucose augmented injury prior to reperfusion compared with
simulated ischemia. Inhibition of oxygen radical generation using the
metal chelator 1,10-phenanthroline reduced cell death from 73% to 40%
after reperfusion (p=0.001). We conclude that simulated reperfusion
significantly augments the cellular membrane damage elicited by
simulated ischemia in isolated cardiomyocytes devoid of other
factors, and suggest that reactive oxygen species, perhaps from the
mitochondria, participate in this injury.
Received 31 May 1995; accepted in final form 11 September 1995.
APS Manuscript Number H501-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95