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

Artikel i vetenskaplig tidskrift
Författare Lars O Karlsson
Niklas Bergh
Lizhen Li
E. Bissessar
I. Bobrova
G. J. Gross
Levent Akyürek
Lars Grip
Publicerad i European journal of pharmacology
Volym 674
Nummer/häfte 2-3
Sidor 378-383
ISSN 1879-0712
Publiceringsår 2012
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor 378-383
Språk en
Länkar dx.doi.org/10.1016/j.ejphar.2011.11...
Ämnesord 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
Ämneskategorier Klinisk medicin

Sammanfattning

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.

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