Effects of combined helium pre/post-conditioning on the brain and heart in a rat resuscitation model

Abstract

Background: The noble gas helium induces cardio- and neuroprotection by pre- and post-conditioning. We investigated the effects of helium pre- and post-conditioning on the brain and heart in a rat resuscitation model.

Methods: After approval by the Animal Care Committee, 96 Wistar rats underwent cardiac arrest for 6 min induced by ventricular fibrillation. Animals received 70% helium and 30% oxygen for 5 min before cardiac arrest and for 30 min after restoration of spontaneous circulation (ROSC). Control animals received 70% nitrogen and 30% oxygen. Hearts and brains were excised after 2, 4 h or 7 days. Neurological degeneration was evaluated using TUNEL and Nissl staining in the hippocampal CA-1 sector. Cognitive function after 7 days was detected with the tape removal test. Molecular targets were measured by infrared western blot. Data are shown as median [Interquartile range].

Results: Helium treatment resulted in significantly less apoptosis (TUNEL positive cells/100 pixel 73.5 [60.3-78.6] vs.78.2 [70.4-92.9] P = 0.023). Changes in Caveolin-3 expression in the membrane fraction and Hexokinase-II in the mitochondrial fraction were observed in the heart. Caveolin-1 expression of treated animals significantly differed from control animals in the membrane fraction of the heart and brain after ROSC.

Conclusion: Treatment with helium reduced apoptosis in our resuscitation model. Differential expression levels of Caveolin-1, Caveolin-3 and Hexokinase II in the heart were found after helium pre- and post-conditioning. No beneficial effects were seen on neurofunctional outcome.