title: Altered cerebrovascular responses after exposure to venoarterial extracorporeal membrane oxygenation: role of the nitric oxide pathway.
abstract: BACKGROUND
  Previous studies in our laboratory on newborn lambs have shown cerebral autoregulation impairment after exposure to venoarterial extracorporeal membrane oxygenation (VA ECMO), with additional studies showing an altered cerebrovascular response to NG-nitro-L-arginine methyl ester in lamb cerebral vessels in this same model.
  
  
  OBJECTIVE
  To further study the mechanisms involved in altered cerebrovascular responses in vessels exposed to VA ECMO.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Research Animal Facility at Children's National Medical Center, Washington, DC.
  
  
  METHODS
  Newborn lambs, 1-7 days of age, 4.76 +/- 0.8 kg (n = 10).
  
  
  METHODS
  Animals randomly assigned two groups, control and VA ECMO, were anesthetized, ventilated, heparinized, and kept in a normal physiologic condition. Control animals were continued on ventilatory support, whereas animals in the VA ECMO groups were placed on VA ECMO, with bypass flows maintained between 120 and 200 mL x kg x min(-1) for 2.5 hrs. Isolated third-order branches of the middle cerebral arteries were studied for myotonic reactivity to increasing intraluminal pressure changes, response to acetylcholine, an endothelium-dependent vasodilator, 3-morpholinyl-sydnoneimine chloride, an endothelium-independent vasodilator, and serotonin, a direct vascular vasoconstrictor. Arterial caliber was monitored using video microscopy.
  
  
  RESULTS
  Myogenic constriction response was significantly decreased in the VA ECMO group compared with the control group (p = .03). Intraluminal acetylcholine caused concentration-dependent arterial dilation in the control group, whereas it resulted in vasoconstriction in the VA ECMO group (p = .008). There were no significant differences in dilation responses to 3-morpholinyl-sydnoneimine chloride and contractile responses to serotonin among the groups.
  
  
  CONCLUSIONS
  Cerebral arteries exposed to VA ECMO had impaired myogenic responses combined with altered endothelial function. The endothelial alteration seems to be mediated through the nitric oxide pathway, with recovery noted after addition of a nitric oxide donor. It can be postulated that these changes may reflect the mechanisms for the impairment of cerebral autoregulation previously reported in this lamb model.
authors.affiliation: Department of Neonatology, Children's National Medical Center, Washington, DC, USA.
authors.forename: Ma
authors.initials: M
authors.lastname: Ingyinn
authors.forename: Khodayar
authors.initials: K
authors.lastname: Rais-Bahrami
authors.forename: Mohan
authors.initials: M
authors.lastname: Viswanathan
authors.forename: Billie L
authors.initials: BL
authors.lastname: Short
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects* / Q000379:methods; D006706:Homeostasis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011897:Random Allocation; D012756:Sheep
chemical_list: D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester