Prolonged Helium Postconditioning Protocols During Early Reperfusion Do Not Induce Cardioprotection In The Rat Heart In Vivo: Role Of Inflammatory Cytokines

Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/ reperfusion- induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S- ketamine ( 150mg/ kg) and diazepam ( 1.5mg/ kg). Regional myocardial ischemia/ reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine- induced neutrophil chemoattractant ( CINC- 3) and interleukin- 1 beta ( IL- 1..) were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC- 3, IL- 1.., interleukin 6 ( IL- 6), and tumor necrosis factor alpha ( TNF..) in myocardial tissue not directly subjected to ischemia/ reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.