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

  • Bull Exp Biol Med. 2015 Oct;159(6):718-21. doi: 10.1007/s10517-015-3057-8.
S Yu Tsibulnikov  1  2 ,  L N Maslov  3  4 ,  A V Mukhomedzyanov  1 ,  A V Krylatov  1  2 ,  M R Tsibulnikova  2 ,  Yu B Lishmanov  1  2
Affiliations
  • 1. Research Institute of Cardiology, Tomsk, Russia.
  • 2. National Research Tomsk Polytechnic University, Tomsk, Russia.
  • 3. Research Institute of Cardiology, Tomsk, Russia. [email protected].
  • 4. National Research Tomsk Polytechnic University, Tomsk, Russia. [email protected].
PMID: 26519268 DOI: 10.1007/s10517-015-3057-8
Abstract

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.

Keywords
heart; postconditioning; reperfusion; κ-opioid receptors.
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