Effect of amiloride a Na+/H+ exchange inhibitor on cardioprotective effect of ischaemic preconditioning: Possible involvement of resident cardiac mast cells

The present study was designed to investigate the effect of amiloride, a Na+/H+ exchange inhibitor on cardioprotective effect of ischaemic preconditioning in isolated rat heart. Four episodes of ischaemic preconditioning and amiloride (174 mu M) treatment markedly decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and infarct size in hearts subjected to 30 min of global ischaemia followed by 120 min of reperfusion. Amiloride (174 mu M) administered during ischaemic preconditioning (Amiloride in Ischaemic Preconditioning), produced no marked effect on LDH and CK release and infarct size. Ischaemic preconditioning and amiloride treatment significantly reduced ischaemia/reperfusion induced release of mast cell peroxidase (MPO). Four episodes of pH (20 mM of ammonium chloride) preconditioning also produced cardioprotection and decreased ischaemia/reperfusion induced release of MPO. It is interesting to note that a significant increase in release of MPO was observed immediately after ischaemic preconditioning and the release was inhibited by amiloride. Morover, similar increase in MPO release was noted immediately after pH preconditioning. These findings tentatively suggest that ischaemic preconditioning and pH preconditioning produced cardioprotective effect by activating Na+/H+ exchange and consequent degranulation of resident cardiac mast cells. Amiloride administered during ischaemic preconditioning attenuated the cardioprotective effect of ischaemic preconditioning. (C) 1997 The Italian Pharmacological Society.