title: Nonselective endothelin receptor antagonist initiated soon after the onset of myocardial infarction may deteriorate 24-hour survival.
abstract: To investigate the effects of endothelin blockade initiated immediately after the onset of myocardial infarction on survival and left ventricular remodeling, treatment with the nonselective receptor antagonist TAK-044 (n = 22) or saline (n = 19) for 3 weeks was initiated immediately after coronary ligation in rats. The 24-h survival rate was significantly lower in the TAK-044 group than in the saline group. The systolic blood pressure 24 h after the onset of myocardial infarction was similar in the saline and TAK-044 groups, although it was significantly lower in the TAK-044 group during the 3-week protocol. Heart weight/tibial length was significantly increased in the TAK-044 group compared with the saline group. As all deaths in the TAK-044 group occurred within 24 h after myocardial infarction, we performed additional experiments using a separate group of rats 12-16 h after myocardial infarction. Plasma and myocardial endothelin-1 levels were significantly increased, and a bolus injection of TAK-044 significantly reduced left ventricular dP/dtmax in these rats that had had a myocardial infarction compared with sham-operated rats. Endothelin receptor blockade initiated immediately after the onset of myocardial infarction may deteriorate acute-phase survival and left ventricular remodeling. Inhibition of the positive inotropic action of endothlin-1 may partially explain the increased 24-h mortality.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kagaya
authors.forename: S
authors.initials: S
authors.lastname: Namiuchi
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: M
authors.initials: M
authors.lastname: Fukuchi
authors.forename: H
authors.initials: H
authors.lastname: Otani
authors.forename: M
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Y
authors.initials: Y
authors.lastname: Yamane
authors.forename: M
authors.initials: M
authors.lastname: Kohzuki
authors.forename: J
authors.initials: J
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality* / Q000503:physiopathology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C088196:TAK 044