Blocking free radical production via adenoviral gene transfer decreases cardiac ischemia-reperfusion injury.
Periods of cardiac ischemia followed by reperfusion can lead to either transient loss of function (stunning) or permanent functional loss stemming from infarction, depending upon the length of the ischemic period. In either case the primary mediator of the injury may by oxygen-derived free radicals generated upon the reestablishment of blood flow. The heart's primary defense against peroxide, glutathione peroxidase, is depleted during ischemia. Thus, the ischemic myocardium might derive significant protection from increased levels of the enzyme, catalase, which can remove hydrogen peroxide in a redox-independent manner. To test these assertions, we studied the ability of adenoviral gene transfer to increase intracellular antioxidant activity via catalase expression. What we observed was that increasing catalase activity in the heart was sufficient to prevent the stunning associated with 15 min of ischemia followed by reperfusion.
Zhu
H L
HL
Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
Stewart
A S
AS
Taylor
M D
MD
Vijayasarathy
C
C
Gardner
T J
TJ
Sweeney
H L
HL
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism*; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006321:Heart / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000628:therapy; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D014162:Transfection; D019076:Transgenes
D000975:Antioxidants; D005609:Free Radicals; D002374:Catalase