TY - JOUR
T1 - Antiarrhythmic mechanisms of beta blocker therapy
AU - Grandi, Eleonora
AU - Ripplinger, Crystal M
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Sympathetic activity plays an important role in modulation of cardiac rhythm. Indeed, while exerting positive tropic effects in response to physiologic and pathologic stressors, β-adrenergic stimulation influences cardiac electrophysiology and can lead to disturbances of the heart rhythm and potentially lethal arrhythmias, particularly in pathological settings. For this reason, β-blockers are widely utilized clinically as antiarrhythmics. In this review, the molecular mechanisms of β-adrenergic action in the heart, the cellular and tissue level cardiac responses to β-adrenergic stimulation, and the clinical use of β-blockers as antiarrhythmic agents are reviewed. We emphasize the complex interaction between cardiomyocyte signaling, contraction, and electrophysiology occurring over multiple time- and spatial-scales during pathophysiological responses to β-adrenergic stimulation. An integrated understanding of this complex system is essential for optimizing therapies aimed at preventing arrhythmias.
AB - Sympathetic activity plays an important role in modulation of cardiac rhythm. Indeed, while exerting positive tropic effects in response to physiologic and pathologic stressors, β-adrenergic stimulation influences cardiac electrophysiology and can lead to disturbances of the heart rhythm and potentially lethal arrhythmias, particularly in pathological settings. For this reason, β-blockers are widely utilized clinically as antiarrhythmics. In this review, the molecular mechanisms of β-adrenergic action in the heart, the cellular and tissue level cardiac responses to β-adrenergic stimulation, and the clinical use of β-blockers as antiarrhythmic agents are reviewed. We emphasize the complex interaction between cardiomyocyte signaling, contraction, and electrophysiology occurring over multiple time- and spatial-scales during pathophysiological responses to β-adrenergic stimulation. An integrated understanding of this complex system is essential for optimizing therapies aimed at preventing arrhythmias.
KW - Arrhythmia
KW - Autonomic drugs
KW - Beta-blockers
KW - Heart failure
KW - Sympathetic stimulation
UR - http://www.scopus.com/inward/record.url?scp=85066794768&partnerID=8YFLogxK
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U2 - 10.1016/j.phrs.2019.104274
DO - 10.1016/j.phrs.2019.104274
M3 - Review article
C2 - 31100336
AN - SCOPUS:85066794768
VL - 146
JO - Pharmacological Research
JF - Pharmacological Research
SN - 1043-6618
M1 - 104274
ER -