Myocardial adaptation to ischemia by oxidative stress induced by
endotoxin.
Maulik, Nilanjana, Masazumi Watanabe, Daniel Engelman, Richard M.
Engelman, Valerian E. Kagan, Elena Kisin, Vladimir Tyurin, Gerald A.
Cordis, and Dipak K. Das.
Cardiovascular Division, Department of Surgery, University of
Connecticut School of Medicine, Farmington, CT; Department of
Surgery, Baystate Medical Center, Springfield, MA; and Department of
Environmental and Occupational Health, University of Pittsburg,
Pittsburg, PA
APStracts 2:0205C, 1995.
While a large amount of oxidative stress is harmful to cells, a small
amount of such stress can enhance the antioxidative defence system of
the cells and protect them from subsequent stress-related injury. The
present study examined whether a small amount of oxidative stress
could provide adequate protection to the heart against
ischemia/reperfusion injury, and if so, by which mechanism. Oxidative
stress was induced by injecting a small amount of endotoxin (0.5
mg/kg) into the rat. Control experiments were performed by injecting
the rats with the same amount of saline. After 24 hr, rats were
sacrificed, hearts isolated, and the effects of ischemia/reperfusion
was studied using an isolated working heart preparation. The
development of oxidative stress was examined by assessing
malonaldehyde production in the heart. The antioxidant defense system
was studied by estimating antioxidant enzyme activities and
ascorbate- as well as thiol- dependent antioxidant reserve. The
results of our study indicated that endotoxin induced oxidative
stress within one hour of treatment, the stress was reduced
progressively and steadily up to 24 hr, at which point it was
slightly lower than the baseline level. The antioxidant enzymes, Mn
-SOD and Cu/Zn-SOD, and glutathione (GSH) reductase were reduced up to
2 hr, and then increased. Mn-SOD and Cu/Zn-SOD were enhanced
significantly compared to baseline values while GSH reductase level
remained the same as baseline level. Catalase increased progressively
up to 24 hr, GSH-peroxidase did not change up to 4 hr, then increased
steadily up to 24 hr. Both thiol- and ascorbate- dependent
antioxidant reserve were enhanced, but the enhancement of the former
was only transitory. After 24 hr, endotoxin provided adequate
protection to the heart from the ischemic/reperfusion injury as
evidenced by improved left ventricular functions and aortic flow. The
results of this study suggest that the induction of oxidative stress
by endotoxin induced adaptive modification to the antioxidants in the
heart, resulting in the strengthening of the antioxidant defense
system. Antioxidant reserve increased progressively reaching the
maximal level after 24 hr when beneficial effects of oxidative stress
adaptation was observed suggesting that oxidative stress adaptation
may play a role in the reduction of myocardial ischemia reperfusion
injury.
Received 2 December 1994; accepted in final form 14 March 1995.
APS Manuscript Number C705-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.