Brief antecedent anoxia preserves mitochondrial function after sustained undersupply: a subcellular correlate to ischemic preconditioning?
BACKGROUND
There is increasing evidence that mitochondria - owning a high degree of autonomy within the cell - might represent the target organelles of the myocardial protection afforded by ischemic preconditioning. It was the aim of the study to investigate a possible subcellular correlate to ischemic preconditioning at the mitochondrial level. In addition, we tested whether this protection depends on mitochondrial ATP-dependent potassium channels (K (ATP)) and an might involve an attenuation of mitochondrial ATP hydrolysis during sustained anoxia.


RESULTS
Sustained anoxia (A, 14 min) and reoxygenation (R) completely inhibited state 3 and state 4 respiration of isolated ventricular mitochondria from Wistar rats. An antecedent brief anoxic incubation (4 min) followed by reoxygenation (2 min) prevented this loss of mitochondrial function. The protection afforded by anoxic preconditioning could be mimicked by the K (ATP) opener diazoxide (30 micromol/l) and was completely inhibited by the K (ATP) blocker 5-hydroxydecanoic acid (300 micromol/l). Structural mitochondrial integrity, as estimated from externalization of the mitochondrial enzymes creatine kinase and glutamateoxalacetate transaminase, remained unchanged between the groups, as did mitochondrial ATP loss during anoxia.


CONCLUSIONS
For the first time, we provide direct evidence for a subcellular preconditioning-like functional mitochondrial adaptation to sustained anoxia. This effect apparently depends on opening of K(ATP) but is independent of ATP preservation.
Vetter
Sven Y
SY
Medizinische Universitätsklinik (Ludolf-Krehl-Klinik), Abteilung Innere Medizin III (Schwerpunkt Kardiologie, Angiologie und Pulmologie), Im Neuenheimer Feld 410, D - 69120, Heidelberg, Germany.
Elsässer
Albrecht
A
Tutdibi
Osman
O
Lang
Sabrina
S
Schoels
Wolfgang
W
Pott
Anja
A
Ackermann
Cordula
C
Reinhard
Constanze
C
Wieland
Felix
F
Katus
Hugo A
HA
Kübler
Wolfgang
W
Vogt
Achim M
AM
D000222:Adaptation, Physiological; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D024443:Aspartate Aminotransferase, Cytoplasmic / Q000378:metabolism; D024442:Aspartate Aminotransferase, Mitochondrial / Q000378:metabolism; D019069:Cell Respiration / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D042541:Intracellular Space / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D051379:Mice; D008929:Mitochondria, Heart / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D024443:Aspartate Aminotransferase, Cytoplasmic; D024442:Aspartate Aminotransferase, Mitochondrial; D003402:Creatine Kinase