Altered adrenergic response in myocytes bordering a chronic myocardial infarction underlies in vivo triggered activity and repolarization instability

Autor: Guillaume Gilbert, Bert Vandenberk, Demetrio J. Santiago, Daniel M. Johnson, Chandan K. Nagaraju, Karin R. Sipido, Rik Willems, H. Llewelyn Roderick, Matthew Amoni, Piet Claus, Rosa Doñate Puertas, Eef Dries, Mouna Abdesselem
Rok vydání: 2020
Předmět:
0301 basic medicine
Physiology
Swine
Myocardial Infarction
Adrenergic
Action Potentials
Aberrant Calcium Signaling and Arrhythmia Mechanisms
0302 clinical medicine
VENTRICULAR-TACHYCARDIA
ABLATION
Medicine
Myocyte
Myocytes
Cardiac
Myocardial infarction
Adrenergic response
TO-BEAT VARIABILITY
Cardiology
cardiovascular system
HEART-FAILURE
ACTION-POTENTIAL RECORDINGS
calcium cycling
CALCIUM-RELEASE
Life Sciences & Biomedicine
CANINE HEART
arrhythmias
Research Paper
medicine.medical_specialty
animal models of human disease
03 medical and health sciences
Adrenergic Agents
In vivo
Ca2+/calmodulin-dependent protein kinase
Internal medicine
Repolarization
Animals
cardiovascular diseases
ARRHYTHMIAS
Science & Technology
business.industry
autonomic nervous system
Neurosciences
Arrhythmias
Cardiac
medicine.disease
Autonomic nervous system
030104 developmental biology
DE-POINTES
DELAYED AFTERDEPOLARIZATIONS
Neurosciences & Neurology
business
030217 neurology & neurosurgery
Zdroj: Repisalud
Instituto de Salud Carlos III (ISCIII)
The Journal of Physiology
ISSN: 0022-3751
Popis: Key points Ventricular arrhythmias are a major complication after myocardial infarction (MI), associated with sympathetic activation. The structurally heterogeneous peri‐infarct zone is a known substrate, but the functional role of the myocytes is less well known.Recordings of monophasic action potentials in vivo reveal that the peri‐infarct zone is a source of delayed afterdepolarizations (DADs) and has a high beat‐to‐beat variability of repolarization (BVR) during adrenergic stimulation (isoproterenol, ISO).Myocytes isolated from the peri‐infarct region have more DADs and spontaneous action potentials, with spontaneous Ca2+ release, under ISO. These myocytes also have reduced repolarization reserve and increased BVR. Other properties of post‐MI remodelling are present in both peri‐infarct and remote myocytes.These data highlight the importance of altered myocyte adrenergic responses in the peri‐infarct region as source and substrate of post‐MI arrhythmias. Abstract Ventricular arrhythmias are a major early complication after myocardial infarction (MI). The heterogeneous peri‐infarct zone forms a substrate for re‐entry while arrhythmia initiation is often associated with sympathetic activation. We studied the mechanisms triggering these post‐MI arrhythmias in vivo and their relation to regional myocyte remodelling. In pigs with chronic MI (6 weeks), in vivo monophasic action potentials were simultaneously recorded in the peri‐infarct and remote regions during adrenergic stimulation with isoproterenol (isoprenaline; ISO). Sham animals served as controls. During infusion of ISO in vivo, the incidence of delayed afterdepolarizations (DADs) and beat‐to‐beat variability of repolarization (BVR) was higher in the peri‐infarct than in the remote region. Myocytes isolated from the peri‐infarct region, in comparison to myocytes from the remote region, had more DADs, associated with spontaneous Ca2+ release, and a higher incidence of spontaneous action potentials (APs) when exposed to ISO (9.99 ± 4.2 vs. 0.16 ± 0.05 APs/min, p = 0.004); these were suppressed by CaMKII inhibition. Peri‐infarct myocytes also had reduced repolarization reserve and increased BVR (26 ± 10 ms vs. 9 ± 7 ms, P
Key points Ventricular arrhythmias are a major complication after myocardial infarction (MI), associated with sympathetic activation. The structurally heterogeneous peri‐infarct zone is a known substrate, but the functional role of the myocytes is less well known.Recordings of monophasic action potentials in vivo reveal that the peri‐infarct zone is a source of delayed afterdepolarizations (DADs) and has a high beat‐to‐beat variability of repolarization (BVR) during adrenergic stimulation (isoproterenol, ISO).Myocytes isolated from the peri‐infarct region have more DADs and spontaneous action potentials, with spontaneous Ca2+ release, under ISO. These myocytes also have reduced repolarization reserve and increased BVR. Other properties of post‐MI remodelling are present in both peri‐infarct and remote myocytes.These data highlight the importance of altered myocyte adrenergic responses in the peri‐infarct region as source and substrate of post‐MI arrhythmias.
Databáze: OpenAIRE
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