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

Background: we previously have shown that glibenclamide (gbc),a sulfonylurea receptor 1-transient receptor potential m4 (sur1-trpm4) 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 sur1 and trpm4 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 ca1 region with similar efficacy,whereas the combination of them had a trend toward better effect. the subunits of sur1-trpm4 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. © 2016 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.