Metabolism of preconditioned myocardium: effect of loss and reinstatement of cardioprotection.
Ischemic preconditioning is associated with slower destruction of the adenine nucleotide pool and a slower rate of anaerobic glycolysis during subsequent ischemic stress. Whether this association is causal is uncertain. Using metabolite levels found at baseline and after a 15 min test episode of ischemia, this study tested for concordance, or lack thereof, between the presence or absence of metabolic features v the presence or absence of the preconditioned state. Dogs were assigned to one of four groups: non-preconditioned control (C), full preconditioning (PC) caused by 10 min ischemia (I)+10 min reperfusion (R), dissipated PC (DPC) caused by 10 min I and 180 min R, or reinstated PC in which PC was reinstated in DPC hearts by another 10 min I and 10 min R. At baseline, PC and RPC hearts had a 25% or more decrease in the adenine nucleotide pool (summation operatorAd), a substantial creatine phosphate (CP) overshoot, and a 4-6 times elevation in tissue glucose (G). Of these changes, the decreased summation operatorAd and the CP overshoot persisted during DPC, whereas only G returned to control. Thus, increased G was the only baseline feature, which was concordant with the preconditioned state. The response to ischemic stress in PC and RPC tissue included less lactate production and much less degradation of the summation operatorAd pool to nucleosides and bases than in the C or DPC groups. Thus, slower destruction of the summation operatorAd pool and slower lactate production during ischemia also were concordant with the PC state. The results support the hypothesis that a reduction in energy demand is an essential component of the mechanism of cardioprotection in preconditioned myocardium. However, the mechanism through which ischemic preconditioning results in lower energy demand remains to be established.
Jennings
R B
RB
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. jenni004@mc.duke.edu
Sebbag
L
L
Schwartz
L M
LM
Crago
M S
MS
Reimer
K A
KA
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D005260:Female; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism*; D011897:Random Allocation; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000227:Adenine Nucleotides; D010725:Phosphocreatine; D019298:Glucose-6-Phosphate; D005947:Glucose