Cardioprotective effects of [5-(2-methyl-5-fluorophenyl)furan-2-ylcarbonyl]guanidine (KR-32568) in an anesthetized rat model of ischemia and reperfusion heart injury.
The effects of a novel sodium/hydrogen exchanger-1 (NHE-1) inhibitor, KR-32568, were studied in an anesthetized rat model of 30 min ischemia/2.5 h reperfusion heart injury. KR-32568 dose-dependently inhibited NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. In our anesthetized rat model, KR-32568 reduced infarct size from 67 (control) to 43 and 24% at 0.1 and 1.0 mg/kg (i.v. bolus, given 10 min before ischemia), respectively. KR-32568 at the same doses also significantly reduced the total number of ventricular premature beats during ischemia/reperfusion from 530 (control) to 266 and 115 beats, ventricular tachycardia (VT) incidence from 51 (control) to 21 and 8, VT duration from 238 s (control) to 63 and 33 s, ventricular fibrillation (VF) incidence from 17 (control) to 8 and 0, and VF duration from 85 s to 18 and 1 s. These results indicate that KR-32568 may exert potent cardioprotective effects in rats via inhibition of sodium/hydrogen exchanger-1.
Roh
Hui-Yul
HY
Department of Applied Biochemistry, Division of Life Science, College of Biomedical and Health Science, Konkuk University, Chungju, Korea.
Jung
In-Sang
IS
Park
Jung-Woo
JW
Yun
Yeo-Pyo
YP
Yi
Kyu-Yang
KY
Yoo
Sung-Eun
SE
Kwon
Suk-Hyung
SH
Chung
Hun-Jong
HJ
Shin
Hwa-Sup
HS
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D011422:Propionates / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018754:Ventricular Dysfunction / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D006146:Guanidines; C507121:KR-32568; D011422:Propionates; D017923:Sodium-Hydrogen Exchangers; C029658:propionic acid