Patients with an impending myocardial infarction may be preconditioned by pre-infarct
angina. Hence, it is important to establish whether ischemic postconditioning is
still effective in preconditioned hearts. We therefore studied in anesthetized rats
the effect of postconditioning after coronary artery occlusions (CAO) of 60 min in
control hearts, hearts preconditioned by a single 15-min CAO (1IPC15) or a triple
3-min CAO (3IPC3). Furthermore, we studied the effect of postconditioning in hearts
that had been pharmacologically preconditioned with intravenous adenosine and in
hearts that had become tolerant to 1IPC15. Postconditioning limited infarct size in
control hearts, but did not afford additional protection in preconditioned hearts,
irrespective of the IPC stimulus. NO synthase inhibition abolished the
cardioprotection by postconditioning, both IPC stimuli, and the combination of
postconditioning and either IPC stimulus. Postconditioning also failed to afford
cardioprotection in hearts protected by adenosine, and in hearts that had become
tolerant to cardioprotection by 1IPC15. In accordance with previous observations,
postconditioning paradoxically increased infarct size following a 30-min CAO. This
detrimental effect was prevented by either IPC stimulus, in a NO synthase–dependent
manner. In conclusion, postconditioning does not afford additional protection in
preconditioned hearts, irrespective of the preconditioning stimulus and the presence
of tolerance to preconditioning. Lack of additional protection may be related to the
observation that postconditioning and preconditioning are both mediated via NO
synthase. In contrast, the increase in infarct size by postconditioning following a
30-min CAO is abolished by either IPC stimulus. These findings indicate that the
interaction between preconditioning and postconditioning is highly dependent on the
duration of index ischemia, but independent of the preconditioning stimulus.
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