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

Eur J Pharmacol. 2012 Jun 5;684(1-3):125-31. doi: 10.1016/j.ejphar.2012.03.045. Epub 2012 Apr 3.

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.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cardiotonic Agents / pharmacology*
  • Enzyme Activation / drug effects
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Health*
  • Heart / drug effects*
  • Heart / physiopathology
  • Helium / pharmacology*
  • Hemodynamics / drug effects
  • Hypertension / complications*
  • Ischemic Postconditioning
  • Male
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Organ Size / drug effects
  • Protein Kinase C-epsilon / metabolism
  • Rats

Substances

  • Cardiotonic Agents
  • Helium
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Protein Kinase C-epsilon
  • Glycogen Synthase Kinase 3