Myocardial ischemia

Correlation of mitochondrial adenine nucleotide and respiratory function

Gregory K. Asimakis, Vincent Conti

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)439-447
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume16
Issue number5
DOIs
StatePublished - 1984

Fingerprint

Adenine Nucleotides
Myocardial Ischemia
Respiration
ATP Translocases Mitochondrial ADP
Mitochondria
Ischemia
Adenine
Heart Mitochondria
Adenosine Monophosphate
Respiratory Rate
Electron Transport
Adenosine Diphosphate
Perfusion
Adenosine Triphosphate

Keywords

  • Adenine nucleotide translocase
  • Adenine nucleotides
  • ATP
  • Ischemia (myocardia)
  • Mitochondrial respiration

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Myocardial ischemia : Correlation of mitochondrial adenine nucleotide and respiratory function. / Asimakis, Gregory K.; Conti, Vincent.

In: Journal of Molecular and Cellular Cardiology, Vol. 16, No. 5, 1984, p. 439-447.

Research output: Contribution to journalArticle

@article{1d2462987e7443ef801a2f3554cc97ab,
title = "Myocardial ischemia: Correlation of mitochondrial adenine nucleotide and respiratory function",
abstract = "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.",
keywords = "Adenine nucleotide translocase, Adenine nucleotides, ATP, Ischemia (myocardia), Mitochondrial respiration",
author = "Asimakis, {Gregory K.} and Vincent Conti",
year = "1984",
doi = "10.1016/S0022-2828(84)80615-X",
language = "English (US)",
volume = "16",
pages = "439--447",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "5",

}

TY - JOUR

T1 - Myocardial ischemia

T2 - Correlation of mitochondrial adenine nucleotide and respiratory function

AU - Asimakis, Gregory K.

AU - Conti, Vincent

PY - 1984

Y1 - 1984

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 - Adenine nucleotide translocase

KW - Adenine nucleotides

KW - ATP

KW - Ischemia (myocardia)

KW - Mitochondrial respiration

UR - http://www.scopus.com/inward/record.url?scp=0021591079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021591079&partnerID=8YFLogxK

U2 - 10.1016/S0022-2828(84)80615-X

DO - 10.1016/S0022-2828(84)80615-X

M3 - Article

VL - 16

SP - 439

EP - 447

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 5

ER -