Helium-induced cardioprotection of healthy and hypertensive rat myocardium in vivo

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-3 beta) and protein kinase C-epsilon (PKC-epsilon). 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 24 h 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-3 beta and PKC-epsilon 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-3 beta and PKC-epsilon. (C) 2012 Elsevier B.V. All rights reserved