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-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 25min ischemia and 120min reperfusion. Rats inhaled 70% helium for 15min after index ischemia (PostC), combined with 15min helium 24h prior to index ischemia (LPC+PostC), a triple intervention with additional 3 short cycles of 5min 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 15min 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.