Atrial Infarction-Induced Spontaneous Focal Discharges and Atrial Fibrillation in Sheep: Role of Dantrolene-Sensitive Aberrant Ryanodine Receptor Calcium Release
| Autor: | Kuljeet Kaur, Masatoshi Yamazaki, Jérôme Kalifa, Stanley Nattel, Roberto Ramos-Mondragón, Carmen R. Valdivia, Alvaro Rojas-Pena, Uma Mahesh R. Avula, Héctor H. Valdivia, Antony Chu, Justus M.B. Anumonwo, Jonathan J Hernandez |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Blotting Western Ischemia Medizin Myocardial Ischemia Infarction 030204 cardiovascular system & hematology Anterior Descending Coronary Artery Ryanodine receptor 2 Dantrolene Article 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine Atrial Fibrillation Medicine Animals Myocytes Cardiac Myocardial infarction Calcium Signaling Heart Atria Sheep business.industry Ryanodine receptor Muscle Relaxants Central Atrial fibrillation Ryanodine Receptor Calcium Release Channel medicine.disease Disease Models Animal Sarcoplasmic Reticulum 030104 developmental biology Cardiology cardiovascular system Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Circulation. Arrhythmia and electrophysiology. 11(3) |
| ISSN: | 1941-3084 |
| Popis: | Background: The mechanisms underlying spontaneous atrial fibrillation (AF) associated with atrial ischemia/infarction are incompletely elucidated. Here, we investigate the mechanisms underlying spontaneous AF in an ovine model of left atrial myocardial infarction (LAMI). Methods and Results: LAMI was created by ligating the atrial branch of the left anterior descending coronary artery. ECG loop recorders were implanted to monitor AF episodes. In 7 sheep, dantrolene—a ryanodine receptor blocker—was administered in vivo during the 8-day observation period (LAMI-D, 2.5 mg/kg, IV, BID). LAMI animals experienced numerous spontaneous AF episodes during the 8-day monitoring period that were suppressed by dantrolene (LAMI, 26.1±5.1; sham, 4.3±1.1; LAMI-D, 2.8±0.8; mean±SEM episodes per sheep, P 3 H]ryanodine binding to cardiac RyR2 (ryanodine receptors) in the ischemic zone. Dantrolene restored the physiological binding of CaM to RyR2. Conclusions: Atrial ischemia causes spontaneous AF episodes in sheep, caused by SFDs that initiate reentry. Nitroso–redox imbalance in the ischemic zone is associated with intense reactive oxygen species production and altered RyR2 responses to CaM. Dantrolene administration normalizes the CaM response, prevents LAMI-related SFDs, and AF initiation. These findings provide novel insights into the mechanisms underlying ischemia-related atrial arrhythmias. |
| Databáze: | OpenAIRE |
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