IMPROVED TOLERANCE TO HYDROGEN PEROXIDE-INDUCED OXIDATIVE STRESS IN
AGED RAT HEARTS
J.W. Starnes and R.P. Taylor
Department of Kinesiology
University of Texas
Austin, TX 78712
Reactive oxygen species, which includes hydrogen peroxide (H2O2), have
been implicated in myocardial injury after ischemia-reperfusion injury
and in the process of cardiac aging. The purpose of this study was to
determine the effect of age on the ability of the heart to tolerate
direct exposure of H2O2. Isolated perfused working hearts from
2.5-month, 8-month, and 23-month male F344 rats were perfused with
H2O2-free buffer for approximately 25 minutes to establish a stable
baseline function and then with 125 micomolar H2O2 for 20 minutes
followed by a 10-minute washout with H2O2-free buffer. Pre-H2O2
baseline function (cardiac output x systolic pressure) was 4,197283
ml/min/g x mmHg at 2.5-mo (n, 4,455202 at 8-mo (, and 3,559159 at 23-mo
(n . H2O2 exposure progressively decreased cardiac performance
throughout the 20-minute period in all groups; however, the decline in
the oldest group was significantly attenuated. After 20 minutes of
exposure, cardiac function (% of pre-H2O2 baseline) was 22.23.5,
20.12.4, and 37.74.9 in the 2.5-, 8-, and 23-mo groups, respectively.
Leakage of lactate dehydrogenase (LDH), a marker of tissue necrosis,
was measured at 5-minute intervals throughout perfusion. LDH release
during the 20-minute H2O2 exposure did not increase compared to
baseline in the 2.5- or 23-mo groups, but was elevated 1.8-fold at 20
minutes in the 8-mo group (p<0.05). LDH release increased in all
groups during the 10-minute washout period; however, the amount
released by the oldest group was significantly less than the other
groups and the amount released by the 8-mo group was significantly
greater than the other groups. At the end of the perfusion, LDH
release (mU/min/g) was 70.72.6, 142.211.5, and 35.75.4 in the 2.5-, 8-,
and 23-mo groups, respectively (P<0.05 vs any group). The results of
this study indicate that aged rat hearts can tolerate H2O2-induced
oxidative stress better than hearts from younger animals.
Supported Am. Heart Assoc., Texas Affiliate
Key words:
ischemia-reperfusion, free radical, perfused heart, F344 rat
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