Ischemic preconditioning and intracellular ph: a 31p-nmr study in
the isolated rat heart.
Cave, Alison C., and Pamela B. Garlick.
Division of Radiological Sciences, 18th Floor of the Guy s Tower,
Guy s Hospital, London, SE1 9RT
APStracts 3:0336H, 1996.
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 ischemia (I) - 3
min reperfusion (R) - 5 min I - 5 min R) or 4x (5min I - 5 min 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
-Hydroxyethyl]piperazine-N -[2-ethanesulfonic acid] (Hepes) to the
buffer to alleviate acidosis, and (2) increased pre-ischemic glycogen
content to exacerbate acidosis. All hearts were subjected to 40min
ischemia - 40min reperfusion. 31P-NMR was used to measure ATP, PCr,
Pi and intracellular pH. Despite 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, 4x5 Pc, Pc - Hepes and PC fasted, respectively,
compared with their controls (36 9, 17 7 and 20 10% of baseline in
control, control - Hepes and control fasted respectively; pH at end
ischaemia = control, 6.31 0.02; preconditioned, 6.35 0.03; (4x5)
-preconditioned, 6.35 0.04; control - Hepes, 6.40 0.10; preconditioned
- Hepes, 6.56 0.07; control (fasted), 6.46 0.03; preconditioned
(fasted), 6.43 0.01)). No significant differences were observed
between groups in ATP, PCr or Pi upon reperfusion. Thus, the
mechanism of preconditioning in glucose-perfused hearts does not
depend upon 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 upon reperfusion.
Received 11 October 1995; accepted in final form 13 August 1996.
APS Manuscript Number H949-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996