Hypothermia and anesthetic postconditioning influence the expression and activity of small intestinal proteins possibly involved in ischemia/reperfusion-mediated events following cardiopulmonary resuscitation

Abstract

Aim of the studySuccessful resuscitation after cardiac arrest is typically associated with cerebral and myocardial ischemia/reperfusion (I/R)-injury. Recently, we have demonstrated effects of therapeutic hypothermia (HT) and postconditioning with the volatile anesthetic sevoflurane (SEV) on I/R-mediated mechanisms in the heart and brain [Meybohm et al., PLoS One, 2009; Meybohm et al., Crit Care, 2010]. As the intestine is also highly susceptible to I/R-injury, we investigated the influence of HT and SEV on intestinal I/R-mediated events induced by cardiac arrest and successful resuscitation. MethodsEffects of I/R, HT (12h, 33°C) and a combination of HT with SEV (12h, 2.0vol%) were evaluated in a pig model of cardiac arrest and successful cardiopulmonary resuscitation. Western blotting, ELISA, caspase-3/7 assays, myeloperoxidase (MPO) quantifications and gelatine zymography were performed using intestinal tissue derived 24h after return of spontaneous circulation. ResultsCompared to the normothermia control, HT and HT+SEV resulted in a significant increase in intestinal HIF-1α protein expression (P<0.05). Tissue concentrations of IL-1β were significantly reduced in the HT and HT+SEV group (P<0.05), whereas a reduction of IL-10 levels was only detected in the intestine of animals treated with HT+SEV (P<0.05). A statistically significant increase of intestinal MPO activity was found in the HT+SEV group (P<0.01). Activities of caspase-3 and 7 or matrixmetalloproteinase-2 were not changed in any of the groups investigated, the activity of matrixmetalloproteinase-9 was, however, significantly increased in the HT+SEV group (P<0.05). ConclusionHT and postconditioning with SEV influence the expression and activity of several small intestinal proteins that are possibly involved in intestinal I/R-mediated events following successful cardiopulmonary resuscitation.