Monophasic action potentials and Ca(2+) transients in ischaemically preconditioned rabbit ventricular muscle

L.R.C. Dekker, E. van Bavel, T. Opthof, R. Coronel, M.J. Janse

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: ATP-sensitive K(+) (KATP) channels play an important role in the protective mechanism underlying ischaemic preconditioning. Ample evidence indicates, however, that action potential shortening is not a prerequisite for the cardioprotective effect of preconditioning.

METHODS: Monophasic action potential duration (MAPD), tissue resistance, intracellular Ca(2+) (Indo-1) and mechanical activity were simultaneously assessed in arterially perfused rabbit papillary muscles. We studied four experimental protocols preceding sustained ischaemia: 1. control perfusion (n=6), 2. ischaemic preconditioning (PC; n=4), 3. pretreatment with a KATP channel blocker, glibenclamide (15 μmol/1), prior to ischaemic preconditioning (PC+glib; n=3), 4. glibenclamide pretreatment only (Glib; n=2).

RESULTS: In the PC group an increase in the diastolic Ca(2+) level and a prolongation of the Ca(2+) transient just prior to the induction of sustained ischaemia correlate to the postponement of the onset of irreversible ischaemic damage, as established by a rise in [Ca(2+)]i, electrical uncoupling and contracture. Glibenclamide antagonised these changes in the Ca(2+) transient and the cardioprotection induced by preconditioning. MAPD was equal in all experimental groups.

CONCLUSIONS: Prolongation of the Ca(2+) transient and increase of diastolic [Ca(2+)]i just prior to the induction of sustained ischaemia and not action potential shortening are involved in the cardioprotective effect of ischaemic preconditioning. Therefore, a glibenclamide-sensitive mechanism, other than the sarcolemmal KATP channels, is involved in the protective effect of ischaemic preconditioning. Changes in Ca(2+) metabolism may play a crucial role in ischaemic preconditioning.

Original languageEnglish
Pages (from-to)62-69
Number of pages8
JournalNetherlands Heart Journal
Volume11
Issue number2
Publication statusPublished - Feb 2003
Externally publishedYes

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