Effect of ischemic preconditioning on mitochondrial oxidative phosphorylation and high energy phosphates in rat hearts.
The ability of ischemic preconditioning (IP) to protect the myocardium against prolonged ischemia may derive from improved energy balance. We therefore examined myocardial energy metabolism and mitochondrial oxidative phosphorylation in isolated perfused rat hearts which were either subjected (IP group), or not subjected (control group), to preconditioning prior to 30 min sustained ischemia and 30 min reperfusion. Preconditioning was achieved with two cycles of 5 min ischemia followed by 5 min reperfusion. Recovery of myocardial function was significantly greater, and creatine kinase release was significantly lower, in the IP group. Although ATP hydrolysis during the sustained ischemia remained unchanged in both groups, greater preservation of high energy phosphate (eg. ATP and CP) was observed in the IP group after reperfusion. CP content immediately after preconditioning greatly exceeded pre-ischemic values. Lactate production during the sustained ischemia was significantly lower in the IP group, suggesting a decrease in anaerobic glycolysis and a probable attenuation of intracellular acidosis. Oligomycin-sensitive mitochondrial ATPase activity in the control group was significantly decreased both after the sustained ischemia and the reperfusion, but in the IP group it did not change after the preconditioning, sustained ischemia, or reperfusion. Although atractyloside-inhibitable adenine nucleotide translocase activity was markedly decreased during sustained ischemia in both groups, its activity was significantly higher after reperfusion in the IP group. These data suggest that (1) mitochondrial ATPase contributes only slightly to ATP depletion during sustained ischemia, (2) both the CP overshoot phenomenon and the decrease in anaerobic glycolysis can be attributable to cardioprotection during the sustained ischemia, and (3) the preservation of ATPase and adenine nucleotide translocase activities may be a possible explanation for the restoration of high energy phosphates after sustained ischemia-reperfusion injury in the preconditioned hearts of rats.
Kobara
M
M
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Tatsumi
T
T
Matoba
S
S
Yamahara
Y
Y
Nakagawa
C
C
Ohta
B
B
Matsumoto
T
T
Inoue
D
D
Asayama
J
J
Nakagawa
M
M
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000693:Anaerobiosis; D000818:Animals; D003401:Creatine / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D005069:Evaluation Studies as Topic; D006019:Glycolysis / Q000502:physiology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007773:Lactates; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D003402:Creatine Kinase; D000251:Adenosine Triphosphatases; D003401:Creatine