Minocycline fails to improve neurologic and histologic outcome after ventricular fibrillation cardiac arrest in rats

• 作者: Andreas Janata Caleb D Wilson Ingrid AM Magnet Jason P Stezoski Keri Janesko-Feldman Kristin L Schreiber Patrick M Kochanek Tomas Drabek
• 来源期刊: 世界重症医学杂志
• 学科: 医学
• 关键词: Heart arrest/pathology CARDIOPULMONARY RESUSCITATION Survival rate Neurons/drug EFFECTS Microglia/drug EFFECTS Minocycline/pharmacology
• 年，卷（期）: 2019,（7）
• 页码范围: 106-119
• 页数: 14页
• 分类号: R74

摘要

BACKGROUND Prolonged cardiac arrest(CA)produces extensive neuronal death and microglial proliferation and activation resulting in neuro-cognitive disabilities.Among other potential mechanisms,microglia have been implicated as triggers of neuronal death after hypoxic-ischemic insults.Minocycline is neuroprotective in some brain ischemia models,either by blunting the microglial response or by a direct effect on neurons.AIM To improve survival,attenuate neurologic deficits,neuroinflammation,and histological damage after ventricular fibrillation(VF)CA in rats.METHODS Adult male isoflurane-anesthetized rats were subjected to 6 min VF CA followed by 2 min resuscitation including chest compression,epinephrine,bicarbonate,and defibrillation.After return of spontaneous circulation(ROSC),rats were randomized to two groups:(1)Minocycline 90 mg/kg intraperitoneally(i.p.)at 15 min ROSC,followed by 22.5 mg/kg i.p.every 12 h for 72 h;and(2)Controls,receiving the same volume of vehicle(phosphate-buffered saline).The rats were kept normothermic during the postoperative course.Neurologic injury was assessed daily using Overall Performance Category(OPC;1=normal,5=dead)and Neurologic Deficit Score(NDS;0%=normal,100%=dead).Rats were sacrificed at 72 h.Neuronal degeneration(Fluoro-Jade C staining)and microglia proliferation(anti-Iba-1 staining)were quantified in four selectively vulnerable brain regions(hippocampus,striatum,cerebellum,cortex)by three independent reviewers masked to the group assignment.RESULTS In the minocycline group,8 out of 14 rats survived to 72 h compared to 8 out of 19 rats in the control group(P=0.46).The degree of neurologic deficit at 72 h[median,(interquartile range)]was not different between survivors in minocycline vs controls:OPC 1.5(1-2.75)vs 2(1.25-3),P=0.442;NDS 12(2-20)vs 17(7-51),P=0.328)or between all studied rats.The number of degenerating neurons(minocycline vs controls,mean±SEM:Hippocampus 58±8 vs 76±8;striatum 121±43 vs 153±32;cerebellum 20±7 vs 22±8;cortex 0±0 vs 0±0)or proliferating m