Organ protection by the noble gas helium

The aims of this thesis were to investigate whether helium induces preconditioning in humans, and to elucidate the mechanisms behind this possible protection.
First, we collected data regarding organ protective effects of noble gases in general, and of helium in particular (chapters 1-3). In chapter 4 we demonstrated that helium inhalation in healthy volunteers had no negative side effects on the innate human immune system and the ability to respond to pathogens in vitro. After that, we showed that helium induces preconditioning in humans and protects against postischemic endothelial damage following forearm ischemia-reperfusion in healthy volunteers. (chapter 5). In chapter 6 we conducted a clinical trial, including 125 patients undergoing coronary artery bypass graft surgery, investigating whether helium affects signal transduction kinases (P38 mitogen-activated protein kinase, extracellular signal–regulated kinase-1/2, protein kinase C-ε or heat shock protein-27) or postoperative troponin release.
The second aim of this thesis was to elucidate the mechanisms behind helium conditioning, which we investigated in cultured endothelial cells in vitro. In chapter 7 we demonstrate prolonged helium exposure (30 minutes) in endothelial cells surprisingly aggravated oxidative stress induced cell damage, increasing cell death. In chapter 9 we showed exposure to helium (20 minutes) increased cortical localization of F-actin fibers and decreases permeability via caveolin-1. Focusing on the possible effect of caveolin in the buoyant fraction (supernatant or plasma), we investigated whether plasma from healthy volunteers undergoing helium or ischemic conditioning protected endothelial cells against hypoxia in vitro (chapter 8 and 10).