Prospects of Using of κ-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia/Reperfusion

• DOI: 10.1007/s10517-015-3057-8
• Publication Date: 2015-10-30T23:59:40Z
• Authors: S. Yu. Tsibulnikov; L. N. Maslov; A. V. Mukhomedzyanov; A. V. Krylatov; M. R. Tsibulnikova; Yu. B. Lishmanov
• Keywords: 0303 health sciences; Cardiotonic Agents; Pyrrolidines; Receptors, Opioid, kappa; 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Myocardial Ischemia; Myocardial Reperfusion Injury; Rats; 03 medical and health sciences; Ischemic Preconditioning, Myocardial; Animals; Rats, Wistar; Anti-Arrhythmia Agents

We studied the ability of the agonist of κ1-opioid receptors U-50,488 in doses of 0.1 and 1 mg/kg to simulate ischemic pre- and postconditioning of the heart and κ-opioid receptors ICI 199,441 in a dose of 0.1 mg/kg to simulate the antiarrhythmic effect of heart preconditioning. The duration of ischemia was 10 or 45 min and the duration of reperfusion was 10 min or 2 h. Administration of 1 mg/kg U-50,488 both before ischemia and 5 min before reperfusion produced a pronounced antiarrhythmic effect. U-50,488 injected 5 min before reperfusion 2-fold reduced the ratio of infarction to risk area. Administration of ICI 199,441 in a dose of 0.1 mg/kg 15 min before ischemia produced a potent antiarrhythmic effect. Antiarrhythmic effect of κ-opioid receptor agonists depended on activation of κ-opioid receptors.