Projects per year
Abstract
Background—We tested the hypothesis that ischemia-induced ventricular fibrillation (VF) is facilitated by platelets, trapped regionally in the ischemic zone (IZ) and activated to release arrhythmogenic secretome. Methods and Results—In a randomized study, in rat blood-free buffer-perfused isolated hearts, IZ territory (34 ± 1% of LV) was selected so that ischemia evoked VF in only 42% of controls. VF incidence was increased to 91% (P<0.05) by coronary ligation-induced trapping of freshly-prepared autologous platelets (infused before and during coronary ligation, with trapping confirmed by 111In-labeled platelet autoradiographic imaging). Trapping of platelet secretome prepared ex vivo, or platelet sized fluorospheres, did not increase ischemia-induced VF incidence. Secretome alone did however evoke VF in two sham coronary-ligated hearts. Perfusion did not activate infused platelets in sham coronary-ligated hearts, whereas ligation activated trapped platelets (assessed by thromboxane release). In a separate study, trapping whole heparinised blood mimicked the ability of trapped platelets to increase VF incidence. This effect was not prevented by 5+day oral pre-treatment in vivo with clopidogrel (10 mg/kg/day) or indomethacin (2.4 mg/kg/day). Conclusions—Platelets facilitate VF during acute ischemia independently of their ability to participate in occlusive thrombosis. Moreover the effect is unresponsive to commonly used antiplatelet drugs. Labile secretome constituents appear to be responsible. This opens a novel avenue for antiarrhythmic drug research.
| Original language | English |
|---|---|
| Article number | N/A |
| Pages (from-to) | 995-1001 |
| Number of pages | 7 |
| Journal | Circulation-Arrhythmia And Electrophysiology |
| Volume | 6 |
| Issue number | 5 |
| Early online date | 31 Aug 2013 |
| DOIs | |
| Publication status | Published - Oct 2013 |
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- 2 Finished
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PET imaging of cardiac hypoxia and ischaemia with radiocopper complexes
Southworth, R. (Primary Investigator), Blower, P. (Co-Investigator), Marsden, P. (Co-Investigator) & Nagel, E. (Co-Investigator)
1/04/2010 → 10/10/2013
Project: Research
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BHF Centre of Research Excellence
Avkiran, M. (Primary Investigator), Blower, P. (Primary Investigator), Botnar, R. (Primary Investigator), Chowienczyk, P. (Primary Investigator), Eaton, P. (Primary Investigator), Ehler, E. (Primary Investigator), Garcia-Manyes, S. (Primary Investigator), Gautel, M. (Primary Investigator), Geissmann, F. (Primary Investigator), Hussain, M. (Primary Investigator), Irving, M. (Primary Investigator), Kalra, L. (Primary Investigator), Marber, M. (Primary Investigator), Mayr, M. (Primary Investigator), Nagel, E. (Primary Investigator), Otsu, K. (Primary Investigator), Razavi, R. (Primary Investigator), Ridley, A. (Primary Investigator), Shah, A. (Primary Investigator), Shanahan, C. (Primary Investigator), Smith, N. (Primary Investigator), Xu, Q. (Primary Investigator), Alastruey, J. (Co-Investigator), Ameer-Beg, S. (Co-Investigator), Bishop, M. (Co-Investigator), Brain, S. (Co-Investigator), Burgoyne, J. (Co-Investigator), Conte, M. (Co-Investigator), Dhanjal, T. (Co-Investigator), Eminaga, S. (Co-Investigator), Eykyn, T. (Co-Investigator), Gee, T. (Co-Investigator), Heintzmann, R. (Co-Investigator), Hughes, S. (Co-Investigator), Iskratsch, T. (Co-Investigator), Ivetic, A. (Co-Investigator), Jones, G. E. (Co-Investigator), Kentish, J. (Co-Investigator), Lamata de la Orden, P. (Co-Investigator), Lombardi, G. (Co-Investigator), Mullen, G. (Co-Investigator), Okonko, D. (Co-Investigator), Parsons, M. (Co-Investigator), Pfuhl, M. (Co-Investigator), Phinikaridou, A. (Co-Investigator), Rodaway, A. (Co-Investigator), Shattock, M. (Co-Investigator), Sinkus, R. (Co-Investigator), Springett, R. (Co-Investigator), Steiner, R. (Co-Investigator), Stroud, M. (Co-Investigator), Sun, Y.-B. (Co-Investigator), Wardle, F. (Co-Investigator), Warren, D. (Co-Investigator), Webb, A. (Co-Investigator), Zampetaki, A. (Co-Investigator), Zeng, L. (Co-Investigator) & academic, A. (Co-Investigator)
1/01/2008 → 31/03/2019
Project: Research