The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade
AIMS:ST-elevation myocardial infarction is associated with high levels of cardiac sympathetic drive and release of the co-transmitter neuropeptide Y (NPY). We hypothesized that despite beta-blockade, NPY promotes arrhythmogenesis via ventricular myocyte receptors. METHODS AND RESULTS:In 78 patients...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2019
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| _version_ | 1797087143676346368 |
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| author | Kalla, M Hao, G Tapoulal, N Tomek, J Liu, K Woodward, L Oxford Acute Myocardial Infarction (Oxami) Study Dall'Armellina, E Banning, A Choudhury, R Neubauer, S Kharbanda, R Channon, K Ajijola, O Shivkumar, K Paterson, D Herring, N |
| author_facet | Kalla, M Hao, G Tapoulal, N Tomek, J Liu, K Woodward, L Oxford Acute Myocardial Infarction (Oxami) Study Dall'Armellina, E Banning, A Choudhury, R Neubauer, S Kharbanda, R Channon, K Ajijola, O Shivkumar, K Paterson, D Herring, N |
| author_sort | Kalla, M |
| collection | OXFORD |
| description | AIMS:ST-elevation myocardial infarction is associated with high levels of cardiac sympathetic drive and release of the co-transmitter neuropeptide Y (NPY). We hypothesized that despite beta-blockade, NPY promotes arrhythmogenesis via ventricular myocyte receptors. METHODS AND RESULTS:In 78 patients treated with primary percutaneous coronary intervention, sustained ventricular tachycardia (VT) or fibrillation (VF) occurred in 6 (7.7%) within 48 h. These patients had significantly (P < 0.05) higher venous NPY levels despite the absence of classical risk factors including late presentation, larger infarct size, and beta-blocker usage. Receiver operating curve identified an NPY threshold of 27.3 pg/mL with a sensitivity of 0.83 and a specificity of 0.71. RT-qPCR demonstrated the presence of NPY mRNA in both human and rat stellate ganglia. In the isolated Langendorff perfused rat heart, prolonged (10 Hz, 2 min) stimulation of the stellate ganglia caused significant NPY release. Despite maximal beta-blockade with metoprolol (10 μmol/L), optical mapping of ventricular voltage and calcium (using RH237 and Rhod2) demonstrated an increase in magnitude and shortening in duration of the calcium transient and a significant lowering of ventricular fibrillation threshold. These effects were prevented by the Y1 receptor antagonist BIBO3304 (1 μmol/L). Neuropeptide Y (250 nmol/L) significantly increased the incidence of VT/VF (60% vs. 10%) during experimental ST-elevation ischaemia and reperfusion compared to control, and this could also be prevented by BIBO3304. CONCLUSIONS:The co-transmitter NPY is released during sympathetic stimulation and acts as a novel arrhythmic trigger. Drugs inhibiting the Y1 receptor work synergistically with beta-blockade as a new anti-arrhythmic therapy. |
| first_indexed | 2024-03-07T02:31:49Z |
| format | Journal article |
| id | oxford-uuid:a77d8660-557c-4a21-8028-78fb488a2b4f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:31:49Z |
| publishDate | 2019 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:a77d8660-557c-4a21-8028-78fb488a2b4f2022-03-27T02:55:03ZThe cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockadeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a77d8660-557c-4a21-8028-78fb488a2b4fEnglishSymplectic Elements at OxfordOxford University Press2019Kalla, MHao, GTapoulal, NTomek, JLiu, KWoodward, LOxford Acute Myocardial Infarction (Oxami) StudyDall'Armellina, EBanning, AChoudhury, RNeubauer, SKharbanda, RChannon, KAjijola, OShivkumar, KPaterson, DHerring, NAIMS:ST-elevation myocardial infarction is associated with high levels of cardiac sympathetic drive and release of the co-transmitter neuropeptide Y (NPY). We hypothesized that despite beta-blockade, NPY promotes arrhythmogenesis via ventricular myocyte receptors. METHODS AND RESULTS:In 78 patients treated with primary percutaneous coronary intervention, sustained ventricular tachycardia (VT) or fibrillation (VF) occurred in 6 (7.7%) within 48 h. These patients had significantly (P < 0.05) higher venous NPY levels despite the absence of classical risk factors including late presentation, larger infarct size, and beta-blocker usage. Receiver operating curve identified an NPY threshold of 27.3 pg/mL with a sensitivity of 0.83 and a specificity of 0.71. RT-qPCR demonstrated the presence of NPY mRNA in both human and rat stellate ganglia. In the isolated Langendorff perfused rat heart, prolonged (10 Hz, 2 min) stimulation of the stellate ganglia caused significant NPY release. Despite maximal beta-blockade with metoprolol (10 μmol/L), optical mapping of ventricular voltage and calcium (using RH237 and Rhod2) demonstrated an increase in magnitude and shortening in duration of the calcium transient and a significant lowering of ventricular fibrillation threshold. These effects were prevented by the Y1 receptor antagonist BIBO3304 (1 μmol/L). Neuropeptide Y (250 nmol/L) significantly increased the incidence of VT/VF (60% vs. 10%) during experimental ST-elevation ischaemia and reperfusion compared to control, and this could also be prevented by BIBO3304. CONCLUSIONS:The co-transmitter NPY is released during sympathetic stimulation and acts as a novel arrhythmic trigger. Drugs inhibiting the Y1 receptor work synergistically with beta-blockade as a new anti-arrhythmic therapy. |
| spellingShingle | Kalla, M Hao, G Tapoulal, N Tomek, J Liu, K Woodward, L Oxford Acute Myocardial Infarction (Oxami) Study Dall'Armellina, E Banning, A Choudhury, R Neubauer, S Kharbanda, R Channon, K Ajijola, O Shivkumar, K Paterson, D Herring, N The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade |
| title | The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade |
| title_full | The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade |
| title_fullStr | The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade |
| title_full_unstemmed | The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade |
| title_short | The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade |
| title_sort | cardiac sympathetic co transmitter neuropeptide y is pro arrhythmic following st elevation myocardial infarction despite beta blockade |
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