TY-12533, a novel Na(+)/H(+) exchange inhibitor, prevents myocardial stunning in dogs.
Anesthetized open-chest dogs were subjected to 15-min myocardial ischemia followed by 2-h reperfusion to induce myocardial stunning. A novel Na(+)/H(+) exchange inhibitor 6,7,8,9-tetrahydro-2-methyl-5H-cyclohepta[b]pyridine-3-carbonylguanidine maleate (TY-12533), administered 10 min before or 10 min after start of ischemia (3 mg/kg/10 min, i.v.), did not affect reductions in regional myocardial wall thickening, blood flow and pH during ischemia, but it significantly improved recovery of the wall thickening and blood flow after reperfusion. These results indicate that TY-12533, even when administered during ischemia, could prevent myocardial stunning without affecting myocardial dysfunction or acidosis induced by brief ischemia.
Aihara
K
K
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, 980-8578, Sendai, Japan.
Hisa
H
H
Sasamori
J
J
Yoneyama
F
F
Yamaguchi
F
F
Satoh
I
I
Satoh
S
S
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008297:Male; D017682:Myocardial Stunning / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D011725:Pyridines; D017923:Sodium-Hydrogen Exchangers; C420123:TY 12533