Targeting TNFα-mediated cytotoxicity using thalidomide after experimental cardiac arrest in rats: An exploratory study.

Cardiac arrest (CA) results in a central and systemic cytokine and inflammatory response. Thalidomide has been reported to be neuroprotective by selectively decreasing TNFα synthesis. We hypothesized that thalidomide would decrease the systemic and organ-specific TNFα/cytokine response and biomarkers of injury in rats subjected to 10 min CA. Naïves, CA treated with vehicle (CA) and CA treated with thalidomide (50 mg/kg; CA+T) were studied (n=6 per group). TNFα and key cytokines were assessed at 3 h after resuscitation in the cortex, hippocampus, striatum, cerebellum, plasma, heart and lung. Neuron specific enolase (NSE), S100b, cardiac troponin T (cTnT) and intestinal fatty acid binding protein (IFABP) were used to assess neuronal, glial, cardiac and intestinal damage, respectively. CA increased TNFα and multiple pro-inflammatory cytokines in plasma and selected tissues with no differences between the CA and CA+T groups in any region. NSE, S100b, cTnT and IFABP were increased after CA or CA+T vs. in the naïve group (all P<0.05) without significant differences between the CA and CA+T groups. In conclusion, CA resulted in a TNFα and cytokine response, with increased biomarkers of organ injury. Notably, thalidomide at a dose reported to improve the outcome in