TY - JOUR
T1 - Nonselective endothelin receptor antagonist initiated soon after the onset of myocardial infarction may deteriorate 24-hour survival
AU - Takahashi, Chikako
AU - Kagaya, Yutaka
AU - Namiuchi, Shigeto
AU - Takeda, Morihiko
AU - Fukuchi, Mitsumasa
AU - Otani, Hiroki
AU - Ninomiya, Mototsugu
AU - Yamane, Yuriko
AU - Kohzuki, Masahiro
AU - Watanabe, Jun
AU - Shirato, Kunio
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Endothelin
KW - Endothelin receptor antagonist
KW - Left ventricular remodeling
KW - Myocardial infarction
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U2 - 10.1097/00005344-200107000-00004
DO - 10.1097/00005344-200107000-00004
M3 - Article
C2 - 11444500
AN - SCOPUS:0034932967
VL - 38
SP - 29
EP - 38
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 1
ER -