Eribis Peptide 94 Mimics Ischemic Preconditioning in Rats with an Acute Myocardial Infarction and has Cardioprotective Effects during Prolonged Ischemia

Objectives: Previously, we demonstrated that a novel enkephalin analogue, Eribis Peptide 94 (EP94), produces a reduction of myocardial infarct size in rats and pigs administrated during occlusion. Since a complete dose-response relationship and the opioid receptor subtype activated by EP94 was not been clearly established, the following study was undertaken. It was also determined if multiple doses of EP94 could produce greater cardioprotective effects similar to those observed with single versus multiple ischemic preconditioning (IPC) stimuli. Methods: We used adult male Sprague-Dawley rats subjected to either 25 or 40 minutes of coronary occlusion followed by 120 minutes of reperfusion. Key findings: A single and triple bolus of 1 μg/kg of EP94 administered iv prior occlusion produced a reduction of infarct size (IS/AAR) by 39% and 45%, correspondingly. Dose-response relationship has been established. All of the opioid receptor antagonists (naloxone, CTOP, naltrindole, nor-BNI) blocked the effect of EP94. Conclusion: EP94 produces a potent cardioprotective effect in rats following single or multiple injections administrated prior occlusion via effects on μ, δ, and κ opioid receptors. Repeated bolus injections of EP94 produced a reduction of IS/AAR when the ischemic period was increased from 25 to 40 minutes.