Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats

Abstract

Background We previously have shown that glibenclamide ( GBC ), a sulfonylurea receptor 1–transient receptor potential M4 ( SUR 1‐ TRPM 4) channel inhibitor, improves survival and neurological outcome after asphyxial cardiac arrest and cardiopulmonary resuscitation ( ACA / CPR ). Here, we further compare the efficacy of GBC with target temperature management ( TTM ) and determine whether the efficacy of GBC is affected by TTM . Methods and Results Male Sprague‐Dawley rats (n=213) subjected to 10‐minute ACA / CPR were randomized to 4 groups after return of spontaneous circulation ( ROSC ): normothermia control ( NT ); GBC ; TTM ; and TTM + GBC . Survival, neurodeficit scores, histological injury, as well as the expressions of SUR 1 and TRPM 4 were evaluated. The 7‐day survival rate was 34.4% (11 of 32) in the NT group, 65% (13 of 20) in the GBC group, 50% (10 of 20) in the TTM group, and 70% (14 of 20) in the TTM + GBC group. Rats that received either GBC , TTM alone, or in combination showed less neurological deficit than NT control at 24, 48, and 72 hours and 7 days after ROSC . Moreover, TTM or GBC ameliorated neuronal degeneration and glial activation in the hippocampal CA 1 region with similar efficacy, whereas the combination of them had a trend toward better effect. The subunits of SUR 1‐ TRPM 4 heterodimers were both strongly upregulated after ACA / CPR and expressed in multiple types of brain cells, but partly suppressed by TTM . Conclusions GBC is comparable to TTM in improving survival and neurological outcome after ACA / CPR . When GBC is given along with TTM , less histological injury tended to be achieved.