-transparent.png){kind=logo}
Preconditioning the heart by brief episodes of ischemia and reperfusion can be cardioprotective to injury from subsequent sustained ischemia and reperfusion. Such protective effects include the reduction of reperfusion-induced arrhythmias. We have previously reported a rapid rise in the second messenger inositol(1,4,5) trisphosphate with post-ischemic reperfusion, which has been implicated in the generation of reperfusion-induced arrhythmia. Given the possible importance of inositol(1,4,5)trisphosphate, studies were performed in isolated perfused rat hearts to determine if preconditioning could reduce the reperfusion-induced rise in inositol(1,4,5) trisphosphate. [3H]Inositol labeled hearts underwent 20 min global ischemia with or without 2 min reperfusion. This was preceded by preconditioning of two or three cycles of 2 or 5 min ischemia separated by 5 or 10 min reperfusion, or by time matched control perfusions. Two min reperfusion following 20 min ischemia in time matched controls caused an increase of [3H]inositol(1,4,5)trisphosphate from 20 +/- 3 cpm/mg protein to 52 +/- 5 cpm/mg protein (mean +/- S.E.M. n = 4, P < 0.01). Preconditioning of three cycles of 5 min ischemia and 5 min reperfusion inhibited the 2 min reperfusion-induced rise in [3H]inositol(1,4,5)trisphosphate (26 +/- 4 cpm/mg protein. P < 0.01 relative to non-preconditioned hearts), however protocols that involved either fewer ischemic cycles or shorter ischemic periods were ineffective. Preconditioning did not affect myocardial ATP levels or norepinephrine release with sustained ischemia and reperfusion. Inhibition of the reperfusion-induced rise in inositol(1,4,5) trisphosphate may provide an explanation for the inhibitory effects of preconditioning on reperfusion-induced arrhythmias.
K E Anderson, and
E A Woodcock
February 1988,
FEBS letters,
K E Anderson, and
E A Woodcock
August 1999,
FEBS letters,
K E Anderson, and
E A Woodcock
May 2002,
Proceedings of the National Academy of Sciences of the United States of America,
K E Anderson, and
E A Woodcock
September 2000,
Clinical and experimental pharmacology & physiology,
K E Anderson, and
E A Woodcock
August 1994,
Science (New York, N.Y.),
K E Anderson, and
E A Woodcock
January 1995,
Journal of receptor and signal transduction research,
K E Anderson, and
E A Woodcock
August 1993,
Biochemical and biophysical research communications,
K E Anderson, and
E A Woodcock
January 1996,
Molecular and cellular biochemistry,
K E Anderson, and
E A Woodcock
February 1999,
Basic research in cardiology,
K E Anderson, and
E A Woodcock
October 1988,
The Biochemical journal,
