The sympathetic nervous system is chronically activated in
heart failure. This results in a reduction in numbers and sensitivity of beta-receptors, making the heart less responsive to the actions of
catecholamines. This is specific to beta-receptors, the adenycyclase system being largely unaffected.
Sympathomimetic agents are still used in patients with
heart failure to augment cardiac contractility, but tachyphylaxis limits their long-term usefulness, and they may actually cause further myocardial damage. On the other hand, beta-blockade can improve sensitivity to
catecholamines and cardiac action in some patients with severe
left ventricular dysfunction, although this treatment can be hazardous and cannot yet be routinely recommended. Partial beta-agonists are theoretically useful since they can provide baseline sympathetic drive while protecting the heart against excessive sympathetic stimulation and down-regulation of beta-receptors.
Xamoterol, a partial agonist with half the sympathetic activity of
isoprenaline, has been shown to be superior to placebo and to
digoxin in patients with mild to moderate
heart failure.