Modulation of the autonomic control of the failing heart.
The failing heart operates with an abnormal combination of heart rate, stroke volume, and enddiastolic volume. This mismatch becomes more evident during exercise of patients with heart failure, when an increase in cardiac output is achieved with higher heart rate, a lower stroke volume and a higher enddiastolic volume. Using the beta 1-adrenoceptor partial agonist xamoterol which lacks beta 2-adrenoceptor agonism the response of the heart to sympathetic stimulation can be modulated. At rest and low levels of exercise xamoterol provides an inotropic support of the heart, whereas it reduces inappropriate tachycardia at higher levels. Thereby, xamoterol tends to normalize the balance of the inotropic and chronotropic control of the failing heart, because cardiac output is increased with a more normal combination of heart rate, stroke volume, and filling pressure. The beneficial effects of xamoterol are discussed as being especially important for failing ischemic hearts, because the balance between energy supply and energy demand may be improved by xamoterol.
Snow
H M
HM
Bioscience II, ICI Pharmaceuticals, Macclesfield, Cheshire, U.K.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology*; D002302:Cardiac Output / Q000187:drug effects; D002303:Cardiac Output, Low / Q000503:physiopathology*; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D006801:Humans; D011412:Propanolamines / Q000494:pharmacology*; D017307:Xamoterol
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D017307:Xamoterol