| Autor: |
Pedersen, Christian M., Venkatasubramanian, Sowmya, Vase, Henrik, Hyldebrandt, Janus A., Contractor, Hussain, Schmidt, Michael R., Bøtker, Hans Erik, Cruden, Nicholas L., Newby, David E., Kharbanda, Rajesh K., Lang, Ninian N. |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
Pedersen, C M, Venkatasubramanian, S, Vase, H, Hyldebrandt, J A, Contractor, H, Schmidt, M R, Bøtker, H E, Cruden, N L, Newby, D E, Kharbanda, R K & Lang, N N 2016, ' Rotigaptide protects the myocardium and arterial vasculature from Ischaemia reperfusion injury ', British Journal of Clinical Pharmacology. Supplement . https://doi.org/10.1111/bcp.12882 |
| ISSN: |
0306-5251 |
| DOI: |
10.1111/bcp.12882 |
| Popis: |
AIMS: Ischaemia-reperfusion injury (IRI) causes impaired endothelial function and is a major component of the adverse effects of reperfusion following myocardial infarction. Rotigaptide increases gap junction conductance via connexin-43. We tested the hypothesis that rotigaptide reduces experimental myocardial infarction size, and ameliorates endothelial IRI in humans.METHODS: Myocardial infarction study: porcine MI was achieved by catheter-induced occlusion of the left anterior descending artery. In a randomized double-blind study, rotigaptide (n = 9) or placebo (n = 10) was administered intravenously as a 10-min bolus prior to reperfusion and continuously during 2 hours of reperfusion. Myocardial infarction size (IS) was assessed as proportion of the area at risk (AAR). Human translational study: forearm IRI was induced in the presence or absence of intra-arterial rotigaptide. In a randomized double-blind study, forearm arterial blood flow was measured at rest and during intra-arterial infusion of acetylcholine (5-20 µg/min; n = 11) or sodium nitroprusside (2 - 8 mg/min; n = 10) before and after intra-arterial infusion of placebo or rotigaptide, and again following IRI.RESULTS: Myocardial infarction study: Rotigaptide treatment was associated with a reduction of infarct size (IS/AAR[%]: 18.7 ± 4.1 [rotigaptide] vs. 43.6 ± 4.2 [placebo], P = 0.006). Human translational study: Endothelium-dependent vasodilatation to acetylcholine was attenuated after ischaemia-reperfusion in the presence of placebo (P = 0.007), but not in the presence of rotigaptide (P = NS). Endothelium-independent vasodilatation evoked by sodium nitroprusside was unaffected by IRI or rotigaptide (P = NS).CONCLUSIONS: Rotigaptide reduces myocardial infarction size in a porcine model and protects from IRI-related endothelial dysfunction in man. Rotigaptide may have therapeutic potential in the treatment of myocardial infarction. This article is protected by copyright. All rights reserved. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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