Ischemic preconditioning and intracellular pH: a 31P NMR study in the isolated rat heart.
The aim of these studies was to investigate whether manipulation of intracellular pH affects preconditioning in isolated buffer-perfused rat hearts. Control and preconditioned [PC; 3 min of ischemia (I) + 3 min of reperfusion (R) + 5 min of I + 5 min of R or 4 x (5 min of I + 5 min of R)] hearts were subjected to two different protocols expected to alter intracellular pH during the sustained ischemic insult: 1) increased extracellular buffering capacity with the addition of 25 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) to the buffer to alleviate acidosis and 2) increased preischemic glycogen content to exacerbate acidosis. All hearts were subjected to 40 min of I + 40 min of R. 31P nuclear magnetic resonance was used to measure ATP, phosphocreatine, Pi, and intracellular pH. Despite a significantly better recovery of function in all PC groups, there were no significant differences in intracellular pH (rate-pressure product = 60 +/- 5, 66 +/- 10, 42 +/- 5, and 57 +/- 8% of baseline in PC, 4 x 5 PC, PC + HEPES, and PC fasted hearts, respectively, compared with 36 +/- 9, 17 +/- 7, and 20 +/- 10% of baseline in control, control + HEPES, and control fasted hearts, respectively; pH at end ischemia: control, 6.31 +/- 0.02; PC, 6.35 +/- 0.03; 4 x 5 PC, 6.35 +/- 0.04; control + HEPES, 6.40 +/- 0.10; PC + HEPES, 6.56 +/- 0.07: control fasted, 6.46 +/- 0.03; PC fasted, 6.43 +/- 0.01). No significant differences were observed among groups in ATP, phosphocreatine, or Pi on reperfusion. Thus the mechanism of preconditioning in glucose-perfused hearts does not depend on an alleviation of intracellular acidosis during the sustained ischemic period. Furthermore, under the conditions of this study, intracellular pH during ischemia did not predict functional recovery on reperfusion.
Cave
A C
AC
Division of Radiological Sciences, Guy's Hospital, London, United Kingdom.
Garlick
P B
PB
D000818:Animals; D004734:Energy Metabolism; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D017208:Rats, Wistar
D010710:Phosphates; D010758:Phosphorus; D006859:Hydrogen; D006003:Glycogen