ABSTRACT
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.
Subject(s)
Adenine Nucleotides/metabolism , Ischemic Preconditioning, Myocardial , Myocardium/metabolism , Phosphocreatine/metabolism , Animals , Coronary Circulation/physiology , Dogs , Female , Glucose/metabolism , Glucose-6-Phosphate/metabolism , Male , Myocardium/chemistry , Random Allocation , Time Factors , Ventricular Fibrillation/physiopathologyABSTRACT
The hemodynamic and metabolic effects of diaspirin crosslinked hemoglobin (DCLHb) were investigated using graded treadmill exercise in swine (n = 5/group). Swine received DCLHb (10% solution, 5 ml/kg) or oncotically-matched human serum albumin (HSA, 5ml/kg). Baseline metabolic and hemodynamic data were similar. In both groups exercise increased hemodynamic parameters. Exercise increased heart rate (HR) from 139 +/- 12 to 293 +/- 28 bpm with DCLHb and from 136 +/- 13 to 314 +/- 13 bpm with HSA. Exercise increased cardiac output (CO) from 5.7 +/- 0.75 to 15.6 +/- 2.01/min in the DCLHb group and from 5.3 +/- 0.48 to 15.7 +/- 0.881/min in the HSA group. However, CO returned to baseline faster with DCLHb upon stopping exercise. The DCLHb-treated group demonstrated a significantly higher oxygen extraction during exercise (12.04 +/- 0.38 vs 9.48 +/- 0.99 ml O2/100 ml blood) and a lower oxygen delivery throughout recovery (74.6 +/- 6.6 vs 102.2 +/- 7.21 O2/min), indicating enhanced oxygen delivery during exercise in the treatment group. DCLHb infusion did not impair metabolic or hemodynamic functions. These data indicate that DCLHb may increase oxygen delivery to working tissue more efficiently than HSA during treadmill exercise in swine.
