Monophasic action potentials and Ca²⁺ transients in ischaemically preconditioned rabbit ventricular muscle

ATP-sensitive K⁺ (K_ATP) 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.

Monophasic action potential duration (MAPD), tissue resistance, intracellular Ca²⁺ (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 K_ATP channel blocker, glibenclamide (15 μmol/1), prior to ischaemic preconditioning (PC+glib; n=3), 4. glibenclamide pretreatment only (Glib; n=2).

In the PC group an increase in the diastolic Ca²⁺ level and a prolongation of the Ca²⁺ 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 [Ca²⁺]_i, electrical uncoupling and contracture. Glibenclamide antagonised these changes in the Ca²⁺ transient and the cardioprotection induced by preconditioning. MAPD was equal in all experimental groups.

Prolongation of the Ca²⁺ transient and increase of diastolic [Ca²⁺]_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 K_ATP channels, is involved in the protective effect of ischaemic preconditioning. Changes in Ca²⁺ metabolism may play a crucial role in ischaemic preconditioning.