Dose-dependent cardioprotection of enkephalin analogue Eribis peptide 94 and cardiac expression of opioid receptors in a porcine model of ischaemia and reperfusion

• Opioids confer cardioprotection after myocardial ischaemia and reperfusion. The primary aim of the present study was to evaluate the cardioprotective effect of different doses of enkephalin analogue Eribis peptide 94 (EP 94) in a porcine model of ischaemia and reperfusion. A secondary aim was to analyse the impact of ischaemia and reperfusion on the expression of opioid receptor subtypes in the porcine heart. Thirty-four anesthetised pigs underwent 40 min of balloon occlusion of the left anterior descending coronary artery followed by four hours of reperfusion. Pigs were given either vehicle (0.9% NaCl) or one of four doses of EP 94 (0.2, 1, 5 or 25 ug/kg at each administration, respectively), intravenously after 26, 33 and 40 min of ischaemia. Hearts were stained to quantify area at risk and infarct size. mRNA and protein expressions of the opioid receptor subtypes were detected with RT-PCR, immunoblotting and immunohistochemistry in the control and ischaemic/reperfused areas. There was a significant dose-response relationship between higher doses of EP 94 and reduced infarct size. Expression of kappa- and delta-opioid receptors was detected at both mRNA and protein levels. In ischaemic/reperfused areas, an increased expression of mRNA for both receptors was observed, whereas only protein expression for the delta subtype was up-regulated. The mu-opioid receptor was not detected.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Animals

Arrhythmias

Cardiac/complications/drug therapy

Cardiotonic Agents/blood/*pharmacology/therapeutic use

Disease Models

Animal

Dose-Response Relationship

Drug

Enkephalins/blood/*pharmacology/therapeutic use

Female

Gene Expression Regulation/*drug effects

Hemodynamics/drug effects

Myocardial Infarction/complications/drug therapy/pathology

Myocardial Ischemia/*drug therapy/metabolism/pathology/physiopathology

Myocardial Reperfusion Injury/*drug therapy/metabolism/pathology/physiopathology

Myocardium/*metabolism/pathology

RNA

Messenger/genetics/metabolism

Receptors

Opioid/genetics/*metabolism

Risk

Swine

Reperfusion injury; Myocardial ischemia; Opioid receptors; Porcine

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)