title: Decreased DNA Disruption in the Porcine Neocortex with Erythromycin Preconditioning during Prolonged Hypothermic Circulatory Arrest: Evidence for Neuroprotection.
abstract: OBJECTIVE
  We have previously reported that the neocortex is selectively vulnerable to injury in an acute porcine model of hypothermic circulatory arrest (HCA) at 18°C. In view of recent evidence showing that pharmacologic preconditioning with a single dose of erythromycin induces tolerance against transient global cerebral ischemia in rats, we hypothesized that erythromycin would reduce the number of apoptotic neurons in the neocortex in an acute porcine model of HCA at 18°C.
  
  
  METHODS
  Fourteen piglets underwent 75 min of HCA at 18°C following pretreatment with erythromycin (25 mg/kg, IV) (n = 8) or vehicle (Normal Saline 0.9%) (n = 6), applied 12 hr before arrest. Three served as normal controls. After gradual rewarming to a temperature of 36°C, treatment animals were sacrificed and brains were perfusion-fixed and cryopreserved. Neuronal apoptosis after HCA was observed morphologically with hematoxylin and eosin staining, and characterized by in situ DNA fragmentation using terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end-labeling (TUNEL) histochemistry.
  
  
  RESULTS
  Pre-ischemic conditioning with a single dose of the antibiotic erythromycin reduced neuronal apoptosis in the neocortex of the porcine brain. TUNEL-positive cells indicating DNA fragmentation and neuronal injury were significantly greater in the neocortex of animals treated with 18°C HCA (2.55 ± 1.17) compared to animals undergoing HCA after erythromycin preconditioning (1.76 ± 0.91) (p ≤ 0.001).
  
  
  CONCLUSIONS
  These results suggest that cerebral protection during HCA may be achieved with erythromycin pharmacological preconditioning in the porcine model.
authors: Cardiothoracic Surgery Department, General Hospital "G. Papanikolaou", Thessaloniki, Greece.|Department of Anatomy-Histology-Embryology, University of Ioannina Medical School, Ioannina, Greece.
authors: Charilaos-Panagiotis C
authors: CP
authors: Koutsogiannidis
authors: Cardiothoracic Surgery Department, General Hospital "G. Papanikolaou", Thessaloniki, Greece.
authors: Olga G
authors: OG
authors: Ananiadou
authors: Cardiothoracic Surgery Department, General Hospital "G. Papanikolaou", Thessaloniki, Greece.
authors: Fotini C
authors: FC
authors: Ampatzidou
authors: Faculty of Veterinary Medicine, Companion Animal Clinic, Thessaloniki, Greece.
authors: Ioannis P
authors: IP
authors: Savvas
authors: Department of Anatomy, University of Athens Medical School, Athens, Greece.
authors: Dimitrios G
authors: DG
authors: Mytilinaios
authors: Department of Anatomy, University of Athens Medical School, Athens, Greece.
authors: Elena N
authors: EN
authors: Nikolopoulou
authors: Department of Anatomy, University of Athens Medical School, Athens, Greece.
authors: Theodore G
authors: TG
authors: Troupis
authors: Department of Anatomy-Histology-Embryology, University of Ioannina Medical School, Ioannina, Greece.
authors: Antonia V
authors: AV
authors: Charchanti
authors: Cardiothoracic Surgery Department, General Hospital "G. Papanikolaou", Thessaloniki, Greece.
authors: George E
authors: GE
authors: Drossos
authors: Department of Anatomy, University of Athens Medical School, Athens, Greece.
authors: Elizabeth O
authors: EO
authors: Johnson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000209:etiology* / Q000517:prevention & control*; D053938:DNA Fragmentation / Q000187:drug effects*; D003864:Depression, Chemical; D004195:Disease Models, Animal; D004917:Erythromycin / Q000008:administration & dosage* / Q000494:pharmacology*; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D007036:Hypothermia, Induced / Q000009:adverse effects*; D019194:Ischemic Preconditioning / Q000379:methods*; D019579:Neocortex / Q000166:cytology / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D000066829:Neuroprotection; D018696:Neuroprotective Agents; D051381:Rats; D013552:Swine; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D004917:Erythromycin