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1 Cardiac Research Laboratory, Department of Cardiothoracic Surgery, and 2 Neurosciences Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Tel Aviv 69978; 3 Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel; and 4 Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1110
The
role of the proapototic Bax gene in ischemia-reperfusion (I/R)
injury was studied in three groups of mice: homozygotic knockout mice
lacking the Bax gene (Bax
/
), heterozygotic mice
(Bax+/
), and wild-type mice (Bax+/+).
Isolated hearts were subjected to ischemia (30 min, 37°C) and then to 120 min of reperfusion. The left ventricular developed force of
Bax-deficient vs. Bax+/+ hearts at stabilization and at 120 min of reperfusion was 1,411 ± 177 vs. 1,161 ± 137 mg and
485 ± 69 vs. 306 ± 68 mg, respectively. Superior cardiac
function of Bax
/
hearts after I/R was accompanied by a
decrease in creatine kinase release, caspase 3 activity, irreversible
ischemic injury, and the number of terminal deoxynucleotidyl
transferase-mediated dUTP nick-end labeling-positive cardiomyocytes.
Electron microscopic evaluation revealed reduced damage to mitochondria
and the nuclear chromatin structure in Bax-deficient mice. In the
Bax+/
hearts, the damage markers were moderate. The
superior tolerance of Bax knockout hearts to I/R injury recommends this
gene as a potential target for therapeutic intervention in patients
with severe and intractable myocardial ischemia.
Bax-deficient hearts; heart; apoptosis
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