title: Helium-induced cardioprotection of healthy and hypertensive rat myocardium in vivo.
abstract: Helium protects healthy myocardium against ischemia/reperfusion injury by early and late preconditioning (EPC, LPC) and postconditioning (PostC). We investigated helium-induced PostC of the hypertensive heart and enhancement by addition of LPC and EPC. We also investigated involvement of signaling kinases glycogen synthase kinase 3 beta (GSK-3β) and protein kinase C-epsilon (PKC-ε). To assess myocardial cell damage, we performed infarct size measurements in healthy Wistar Kyoto (WKY rats, n=8-9) and Spontaneous Hypertensive rats (SHR, n=8-9) subjected to 25 min ischemia and 120 min reperfusion. Rats inhaled 70% helium for 15 min after index ischemia (PostC), combined with 15 min helium 24h prior to index ischemia (LPC+PostC), a triple intervention with additional 3 short cycles of 5 min helium inhalation shortly before ischemia (EPC+LPC+PostC), or no further treatment. In WKY rats, PostC reduced infarct size from 46 ± 2% (mean ± S.E.M) in the control group to 29 ± 2%. LPC+PostC or EPC+LPC+PostC reduced infarct sizes to a similar extent (30 ± 3% and 32 ± 2% respectively). In SHR, EPC+LPC+PostC reduced infarct size from 53 ± 3% in control to 39 ± 3%, while PostC or LPC+PostC alone were not protective; infarct size 48 ± 4% and 44 ± 4%, respectively. Neither PostC in WKY rats nor EPC+LPC+PostC in SHR was associated with an increase in phosphorylation of GSK-3β and PKC-ε after 15 min of reperfusion. Concluding, a triple intervention of helium conditioning results in cardioprotection in SHR, whereas a single intervention does not. In WKY rats, the triple intervention does not further augment protection. Helium conditioning is not associated with a mechanism involving GSK-3β and PKC-ε.
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands.
authors.forename: Gezina T M L
authors.initials: GT
authors.lastname: Oei
authors.forename: Ragnar
authors.initials: R
authors.lastname: Huhn
authors.forename: Andre
authors.initials: A
authors.lastname: Heinen
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.forename: Wolfgang S
authors.initials: WS
authors.lastname: Schlack
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
authors.forename: Nina C
authors.initials: NC
authors.lastname: Weber
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006262:Health; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006371:Helium / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications*; D057775:Ischemic Postconditioning; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats
chemical_list: D002316:Cardiotonic Agents; D006371:Helium; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051744:Protein Kinase C-epsilon; D038362:Glycogen Synthase Kinase 3