title: Impaired NO-mediated vasodilatation in rat coronary arteries after asphyxial cardiac arrest.
abstract: BACKGROUND
  Cardiovascular dysfunction after cardiac arrest is a common finding. It is unknown whether altered endothelium-mediated vasoreactivity contributes to this dysfunction. We hypothesised that cardiac arrest and resuscitation results in impaired endothelial function. This was addressed by measurements of inflammatory and endothelial plasma markers and of endothelium-dependent vasodilatation in coronary and mesenteric arteries in rats after cardiac arrest and resuscitation.
  
  
  METHODS
  Male Sprague Dawley rats underwent either asphyxia-induced cardiac arrest for 5 min and subsequent resuscitation (n = 30) or a sham procedure (control animals, n = 39). Animals were euthanised after 30 min or 2 h. Blood was analysed for TNF-α, IL-1β, IL-6, IL-10, sE-selectin, sP-selectin, sVCAM-1, ICAM-1, VEGF-α and vWF. Arterial rings of the left anterior descending coronary artery and mesenteric resistance arteries were mounted in microvascular myographs, and concentration-response curves were constructed.
  
  
  RESULTS
  The plasma levels of the endothelial markers, sP-selectin and vWF increased following cardiac arrest at both 30 min and 2 h. Acetylcholine-induced endothelium-dependent and mainly nitric oxide (NO)-mediated vasodilatation was impaired in the coronary arteries at 30 min, but not 2 h after resuscitation. Endothelium-derived hyperpolarisation (EDH)-type vasodilatation induced by NS309 and vasodilatation induced by the NO donor sodium nitroprusside was unaltered. In parallel with systemic hypotension, mesenteric arteries exhibited a larger response to NS309 2 h after resuscitation.
  
  
  CONCLUSIONS
  The present results show marked endothelial alterations after cardiac arrest and resuscitation reflected by increased endothelial plasma markers, impaired NO-mediated coronary vasodilatation in the early post-resuscitation phase and enhanced EDH-type vasodilatation in mesenteric arteries later in the post-resuscitation phase.
authors.affiliation: Department of Anaesthesiology, Aarhus University Hospital NBG, Aarhus, Denmark; Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark; Department of Anaesthesiology, Regional Hospital of Randers, Randers, Denmark.
authors.forename: T T
authors.initials: TT
authors.lastname: Troelsen
authors.forename: A
authors.initials: A
authors.lastname: Granfeldt
authors.forename: N
authors.initials: N
authors.lastname: Secher
authors.forename: E K
authors.initials: EK
authors.lastname: Tønnesen
authors.forename: U
authors.initials: U
authors.lastname: Simonsen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001237:Asphyxia / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006323:Heart Arrest / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D009213:Myography; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D007211:Indoles; D020030:Nitric Oxide Donors; D010091:Oximes; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000109:Acetylcholine