Inhibitory effects of pre-ischemic and post-ischemic treatment with FR 168888, a Na+/H+ exchange inhibitor, on reperfusion-induced ventricular arrhythmias in anesthetized rat.
Effects of pre-ischemic and post-ischemic treatment with FR 168888 (5-hydroxymethyl-3-(pyrrol-1-yl) benzoylguanidine methanesulfonate), a Na+/H+ exchange inhibitor, on reperfusion-induced ventricular arrhythmias were examined in an ischemia/reperfusion model of anesthetized rat. FR 168888 (0.3 mg/kg) significantly reduced the incidence of ventricular fibrillation (VF) and mortality induced by reperfusion following 5-min coronary occlusion, when it was intravenously administered 5 min before coronary artery occlusion. Post-ischemic treatment with FR 168888 (0.3-10 mg/kg), i.e. given 3 min after the start of occlusion, reduced the incidence of VF and mortality. In order to examine the optimal time of administration, FR 168888 (3 mg/kg) was administered 1 or 3 min after the start of occlusion or immediately before reperfusion. There was no significant difference in the reduction of VF and mortality among the three post-ischemic treatment groups. FR 168888 (3 and 10 mg/kg) significantly increased the blood pressure during ischemia without affecting the heart rate. These results indicate that FR 168888 has antiarrhythmic effects on reperfusion-induced arrhythmias even administered after coronary occlusion.
Zhu
Bing-Mei
BM
Department of Pharmacology, Yamanashi Medical University, Nakakoma-gun, Japan. hs99d09@stu.yamanashi-med.ac.jp
Miyamoto
Shigeki
S
Kamiya
Kazunori
K
Komori
Sadayoshi
S
Hashimoto
Keitaro
K
D000758:Anesthesia; D000818:Animals; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D006146:Guanidines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D017180:Tachycardia, Ventricular / Q000188:drug therapy; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology
D001592:Benzyl Alcohols; D002316:Cardiotonic Agents; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; C400288:FR 168888