Beta-adrenergic stimulation and myocardial function in the failing heart

TY - JOUR

T1 - Beta-adrenergic stimulation and myocardial function in the failing heart

AU - El-Armouche, Ali

AU - Eschenhagen, Thomas

PY - 2009/12/1

Y1 - 2009/12/1

N2 - The sympathetic nervous system provides the most powerful stimulation of cardiac function, brought about via norepinephrine and epinephrine and their postsynaptic beta-adrenergic receptors. More than 30 years after the first use of practolol in patients with heart failure beta blockers are now the mainstay of the pharmacological treatment of chronic heart failure. Many aspects of their mechanism of action are well understood, but others remain unresolved. This review focuses on a number of questions that are key to further developments in the field. What accounts for and what is the role of beta-adrenergic desensitization, a hallmark of the failing heart? Is part of this adaptation predominantly beneficial and should therefore be reinforced, another part mainly maladaptive and therefore a target for antagonists? Which lessons can be drawn from studies in genetically engineered mice, which from (pharmaco) genetic studies? Finally, what are promising targets downstream of beta-adrenergic receptors that go beyond the current neurohumoral blockade?

AB - The sympathetic nervous system provides the most powerful stimulation of cardiac function, brought about via norepinephrine and epinephrine and their postsynaptic beta-adrenergic receptors. More than 30 years after the first use of practolol in patients with heart failure beta blockers are now the mainstay of the pharmacological treatment of chronic heart failure. Many aspects of their mechanism of action are well understood, but others remain unresolved. This review focuses on a number of questions that are key to further developments in the field. What accounts for and what is the role of beta-adrenergic desensitization, a hallmark of the failing heart? Is part of this adaptation predominantly beneficial and should therefore be reinforced, another part mainly maladaptive and therefore a target for antagonists? Which lessons can be drawn from studies in genetically engineered mice, which from (pharmaco) genetic studies? Finally, what are promising targets downstream of beta-adrenergic receptors that go beyond the current neurohumoral blockade?

KW - Animals

KW - Heart Failure

KW - Humans

KW - Mice

KW - Mice, Knockout

KW - Myocardial Contraction

KW - Pharmacogenetics

KW - Receptors, Adrenergic, beta

U2 - 10.1007/s10741-008-9132-8

DO - 10.1007/s10741-008-9132-8

M3 - SCORING: Journal article

C2 - 19110970

VL - 14

SP - 225

EP - 241

JO - HEART FAIL REV

JF - HEART FAIL REV

SN - 1382-4147

IS - 4

ER -