TY - JOUR
T1 - Myocardial ischemia
T2 - Correlation of mitochondrial adenine nucleotide and respiratory function
AU - Asimakis, Gregory K.
AU - Conti, Vincent R.
N1 - Funding Information:
This work was supported by grants from the American Heart Association (Texas Affiliate), the American Heart Association (82 767), and in part by BRSG S07-RR07205427 and S07-RR07205 awarded by the Biomedical Research Support Grant Program, Division of Research Resources, National Institutes of Health.
PY - 1984/5
Y1 - 1984/5
N2 - State 3 respiration of rat heart mitochondria decreased approximately 60% after 20 min normothermic in vitro ischemia. After 20 min ischemia, the levels of intramitochondrial adenine nucleotides (ATP+ADP+AMP) decreased to approximately 20% of control values, with a rapid loss between 10 and 20 min. Also, the exchangeable adenine pool of the mitochondria decreased 60% after 20 min ischemia. State 4 respiration was not affected by the ischemic insult. The adenine nucleotide translocase activities of mitochondria from control and ischemic hearts were too high to measure accurately. Therefore, the effects of ischemia on adenine nucleotide translocase activity could not be established. However, 1 μm carboxyatractyloside did not impair state 3 respiration of control mitochondria, but did inhibit the adenine translocase activity by at least 80%. Moreover, titration of state 3 respiration with carboxyatractyloside produced sigmoidal curves for mitochondria from control and ischemic tissue. State 3 respiration correlated well with the total mitochondrial adenine nucleotides and the exchangeable adenine pool (r=0.63 and 0.78, respectively). Data collected from isolated perfused rat hearts also showed a good correlation between state 3 respiration and the exchangeable adenine nucleotides (r=0.92). In this study, mitochondria were isolated from hearts that were either perfused, made ischemic for 30 min by aortic cross-clamp, or reperfused for 10 min after the aortic cross-clamp. The slopes and y-intercepts of the regression lines were similar for the in vitro ischemic and the perfusion studies. There was no significant difference between the effects of ischemia on the state 3 and uncoupled respiratory rates. The results of this study suggest that mitochondrial dysfunction associated with myocardial ischemia cannot be attributed to loss of adenine nucleotide translocase activity, but there is a good correlation between electron transport activity and intramitochondrial adenine nucleotide levels.
AB - State 3 respiration of rat heart mitochondria decreased approximately 60% after 20 min normothermic in vitro ischemia. After 20 min ischemia, the levels of intramitochondrial adenine nucleotides (ATP+ADP+AMP) decreased to approximately 20% of control values, with a rapid loss between 10 and 20 min. Also, the exchangeable adenine pool of the mitochondria decreased 60% after 20 min ischemia. State 4 respiration was not affected by the ischemic insult. The adenine nucleotide translocase activities of mitochondria from control and ischemic hearts were too high to measure accurately. Therefore, the effects of ischemia on adenine nucleotide translocase activity could not be established. However, 1 μm carboxyatractyloside did not impair state 3 respiration of control mitochondria, but did inhibit the adenine translocase activity by at least 80%. Moreover, titration of state 3 respiration with carboxyatractyloside produced sigmoidal curves for mitochondria from control and ischemic tissue. State 3 respiration correlated well with the total mitochondrial adenine nucleotides and the exchangeable adenine pool (r=0.63 and 0.78, respectively). Data collected from isolated perfused rat hearts also showed a good correlation between state 3 respiration and the exchangeable adenine nucleotides (r=0.92). In this study, mitochondria were isolated from hearts that were either perfused, made ischemic for 30 min by aortic cross-clamp, or reperfused for 10 min after the aortic cross-clamp. The slopes and y-intercepts of the regression lines were similar for the in vitro ischemic and the perfusion studies. There was no significant difference between the effects of ischemia on the state 3 and uncoupled respiratory rates. The results of this study suggest that mitochondrial dysfunction associated with myocardial ischemia cannot be attributed to loss of adenine nucleotide translocase activity, but there is a good correlation between electron transport activity and intramitochondrial adenine nucleotide levels.
KW - ATP
KW - Adenine nucleotide translocase
KW - Adenine nucleotides
KW - Ischemia (myocardia)
KW - Mitochondrial respiration
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U2 - 10.1016/S0022-2828(84)80615-X
DO - 10.1016/S0022-2828(84)80615-X
M3 - Article
C2 - 6737484
AN - SCOPUS:0021591079
SN - 0022-2828
VL - 16
SP - 439
EP - 447
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 5
ER -