Helium-induced late preconditioning in the rat heart in vivo.

A recent study showed that the noble gas helium induces early myocardial preconditioning. Cyclooxygenase-2 (COX-2) has been shown to be an important mediator in the signal transduction of late preconditioning. In the present study, we investigated whether helium induces late preconditioning in a concentration-dependent, time-dependent, or in both manner and whether COX-2 activity, mitochondrial function, or both are involved.The study was performed in male Wistar rats and consisted of two parts. In part 1, late preconditioning was achieved by administration of 70%, 50%, 30%, and 10% helium for 15 min 24 h before ischaemia/reperfusion (I/R). Based on the findings of part 1, in additional experiments 30% helium was administered subsequently three and two days before I/R. Furthermore, additional rats were pretreated with the COX-2 inhibitor NS-398 (5 mg kg(-1)) with and without 30% helium. Additional experiments were performed for mitochondrial analysis.Helium concentrations of 70%, 50%, and 30% but not 10% reduced infarct size [He-LPC 70: 37(13)%, He-LPC 50: 34(16)%, He-LPC 30: 40(9)%; each P<0.05 vs55(8)%, He-LPC 10: 53(4)%; P>0.05 vs CONTROL]. Repeated administration of helium did not further enhance cardioprotection. NS-398 completely abolished cardioprotection by 30% helium [He-LPC 30+NS-398: 57(9)%; P<0.05 vs He-LPC 30] but had itself no effect on infarct size [NS-398: 55(9)%; P>0.05 vs CONTROL]. There were no differences in mitochondrial function after helium preconditioning.Helium induces late preconditioning. Cardioprotection is already maximal with administration of one cycle of 30% helium and is abolished by functional blockade of COX-2 activity.