title: Endothelin-1 receptor antagonist prevents deterioration of left ventricular function and coronary flow reserve in brain-dead canine heart.
abstract: BACKGROUND
  Rapid hemodynamic deterioration is caused by induction of brain death, but the exact mechanism is still uncertain. The aim of this study was to investigate the contribution of endothelin-1 by using endothelin-1 receptor antagonist (TAK-044) in a canine brain-death model.
  
  
  METHODS
  Dogs were divided into 2 groups: (1) the TAK group, in which TAK-044 was intravenously injected 30 minutes before brain-death induction at a dose of 3 mg/kg; and (2) the control group. Brain death was induced by rapid inflation of a sub-durally placed balloon catheter. Left ventricular function and coronary flow reserve was compared between the 2 groups.
  
  
  RESULTS
  Brain death caused a transient hyperdynamic response followed by hemodynamic deterioration after 60 minutes in both groups. Left ventricular function, evaluated by the slope of the end-systolic pressure-volume relation was significantly decreased from 7.7 +/- 0.6 to 3.7 +/- 0.3 mm Hg/ml (p < 0.01) in the control group, but was not decreased in the TAK group (7.7 +/- 0.8 to 7.3 +/- 0.9 mm Hg/ml, p = 0.75). Coronary flow reserve, measured by direct injection of acetylcholine (3 microg) into the coronary artery, was significantly reduced at 60 minutes after brain death in the control group (264.8% to 176.6%, p < 0.01), but not in the TAK group (291.2% to 301.3%, p = 0.84). Exactly the same results were obtained when sodium nitroprusside (SNP; 100 microg) was administered.
  
  
  CONCLUSIONS
  TAK-044 can prevent the deterioration of left ventricular function and coronary flow reserve that follows induction of brain death, suggesting that endothelin-1 could play an important role in hemodynamic deterioration by impairment of coronary microcirculation after brain death.
authors.affiliation: Department of Cardiovascular Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Oishi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Tanoue
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kajihara
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Imasaka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Morita
authors.forename: Hisataka
authors.initials: H
authors.lastname: Yasui
mesh_terms: D000818:Animals; D001926:Brain Death; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D004837:Epinephrine / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000097:blood; D010456:Peptides, Cyclic / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D002317:Cardiovascular Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; C088196:TAK 044; D009638:Norepinephrine; D004837:Epinephrine