title: Reduction of cardiac cell death after helium postconditioning in rats: transcriptional analysis of cell death and survival pathways.
abstract: Helium, a noble gas, has been used safely in humans. In animal models of regional myocardial ischemia/reperfusion (I/R) it was shown that helium conditioning reduces infarct size. Currently, it is not known how helium exerts its cytoprotective effects and which cell death/survival pathways are affected. The objective of this study, therefore, was to investigate the cell protective effects of helium postconditioning by PCR array analysis of genes involved in necrosis, apoptosis and autophagy. Male rats were subjected to 25 min of ischemia and 5, 15 or 30 min of reperfusion. Semiquantitative histological analysis revealed that 15 min of helium postconditioning reduced the extent of I/R-induced cell damage. This effect was not observed after 5 and 30 min of helium postconditioning. Analysis of the differential expression of genes showed that 15 min of helium postconditioning mainly caused upregulation of genes involved in autophagy and inhibition of apoptosis versus I/R alone. The results suggest that the cytoprotective effects of helium inhalation may be caused by a switch from pro-cell-death signaling to activation of cell survival mechanisms, which appears to affect a wide range of pathways.
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gezina T M L
authors.initials: GT
authors.lastname: Oei
authors.affiliation: Department of Experimental Surgery, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michal
authors.initials: M
authors.lastname: Heger
authors.affiliation: Department of Experimental Surgery, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rowan F
authors.initials: RF
authors.lastname: van Golen
authors.affiliation: Department of Experimental Surgery, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lindy K
authors.initials: LK
authors.lastname: Alles
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Moritz
authors.initials: M
authors.lastname: Flick
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
authors.affiliation: Department of Experimental Surgery, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Weber
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003326:Coronary Circulation; D006371:Helium / Q000494:pharmacology / Q000627:therapeutic use*; D057775:Ischemic Postconditioning; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D059467:Transcriptome
chemical_list: D002316:Cardiotonic Agents; D012333:RNA, Messenger; D006371:Helium