BJA Advance Access originally published online on March 18, 2009
British Journal of Anaesthesia 2009 102(5):614-619; doi:10.1093/bja/aep042
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Helium-induced late preconditioning in the rat heart in vivo
Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9 1100, DD, Amsterdam, The Netherlands
* Corresponding author. E-mail: n.c.hauck{at}amc.uva.nl
Background: 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.
Methods: 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.
Results: 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 vs Control: 55(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.
Conclusions: 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.
Keywords: complications, myocardial infarction; enzymes, cyclo-oxygenase; heat, ischaemia
These authors contributed equally to this work. 
This work is part of the MD thesis of S.H.