title: Low-dose nitroglycerine improves outcome after cardiac arrest in rats.
abstract: OBJECTIVE
  The aim of this study was to evaluate the outcome of intravenously applied nitroglycerine (NTG, 1μgkg(-1)min(-1) for 1h) after resuscitation from an asphyxia cardiac arrest (ACA) insult. We hypothesized that NTG infused for 1h after the return of spontaneous circulation (ROSC) would improve functional and neuro-morphological outcomes.
  
  
  METHODS
  Adult rats were subjected to 8min of ACA followed by resuscitation. There were three treatment groups: ACA, ACA+NTG and sham operated. Vital and blood parameters were monitored during the 1h post-resuscitation intensive care phase. After survival times of 3, 6, 12, 24, 72h and 7 days, the neurological deficit score (NDS) was measured. Histological evaluation of the hippocampus, cortex, the thalamic reticular nucleus and the caudate-putamen was performed 7 days post insult.
  
  
  RESULTS
  We found that NTG (i) induced significantly higher initial MAP peaks; (ii) resulted in a less-pronounced elevation of heart rates after ROSC with significantly faster normalization to baseline levels; and (iii) influenced glucose metabolism, temporarily elevating blood glucose to non-physiological levels. Even so, NTG (iv) improved the neurological outcome and (v) reduced neurodegeneration, mainly in the hippocampal CA1 region. A significant NTG-associated decrease in blood pressure did not occur.
  
  
  CONCLUSIONS
  The effect of low-dosed NTG applied post-resuscitation appears to be neuroprotective, demonstrated by reduced hippocampal damage and a better NDS, even with temporarily elevated blood glucose to non-physiological levels. Thus, additional studies are needed to evaluate NTG-triggered mechanisms and optimized dosages before clinical translation should be considered. Animal study institutional protocol number: 42502-2-2-947-Uni-MD.
authors.affiliation: Department of Anaesthesiology, University of Magdeburg, Leipziger Strasse 44, Magdeburg, Germany. Electronic address: uwe.ebmeyer@med.ovgu.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Ebmeyer
authors.affiliation: Department of Anaesthesiology, University of Magdeburg, Leipziger Strasse 44, Magdeburg, Germany. Electronic address: torben.esser@med.ovgu.de.
authors.forename: Torben
authors.initials: T
authors.lastname: Esser
authors.affiliation: Institute of Biochemistry and Cell Biology, University of Magdeburg, Leipziger Strasse 44, Magdeburg, Germany. Electronic address: gerburg.keilhoff@med.ovgu.de.
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000517:prevention & control*; D016887:Cardiopulmonary Resuscitation; D006323:Heart Arrest / Q000628:therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D005996:Nitroglycerin / Q000008:administration & dosage*; D017208:Rats, Wistar; D015996:Survival Rate; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D018696:Neuroprotective Agents; D014665:Vasodilator Agents; D005996:Nitroglycerin
keywords: Cardiac arrest; Functional outcome; Hippocampus; Neurodegeneration; Nitroglycerine; Resuscitation