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 β 1-adrenoceptor partial agonist xamoterol which lacks β 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.
KeywordsPlacebo Fatigue Half Life Adrenaline Catecholamine
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- 2.Bainbridge FA (1915) The influence of venous filling upon the rate of the heart. J Physiol 50: 6584Google Scholar
- 4.Barnett DB, Maguire M (1986) Comparison of the effects of chronic infusion of xamoterol and isoprenaline on rat ventricular ß-adrenoceptors. Br J Pharmacol 87: 223 PGoogle Scholar
- 5.Blackwood R, Marlow HR (1988) Xamoterol in the management of patients with exertional breathlessness and fatigue due to cardiac disease. J Am Coll Cardiol 11: 143AGoogle Scholar
- 13.Furnival CM, Linden RJ, Snow JM (1971 a) The inotropic and chronotropic effects of catecholamines on the dog heart. J Physiol 214: 15–28Google Scholar
- 14.Furnival CM, Linden RJ, Snow HM (1971 b) Reflex effects on the heart of stimulating left atrial receptors. J Physiol 218: 447–463Google Scholar
- 15.German and Austrian Study Group (1988) Double-blind placebo-controlled comparison of Digoxin and Xamoterol in chronic heart failure. Lancet 1: 489–493Google Scholar
- 20.Linden RJ, Snow HM (1974) The inotropic state of the heart. In: Linden RJ (ed) Recent advances in physiology. Churchill Livingstone, EdinburghGoogle Scholar
- 22.McCaffrey PM, Riddell JG, Shanks RG (1986) The selectivity of the partial agonist activity of xamoterol in man measured by its effects in the presence of ICI 118551. Br J Pharmacol 89: 594 PGoogle Scholar
- 27.Pouleur H, Rousseau MF, Hanet C, Marlow HF, Charier AA (1987) Left ventricular sensitivity to ß-adrenoceptor-stimulating drugs in patients with ischaemic heart disease and varying degrees of ventricular dysfunction. Cire Res 4 [Suppl 11: 91–95Google Scholar
- 30.Sasayama S, Yokawa S, Akiyama M, Mikawa M, Sakai 0 (1986) Cardiovascular effects of ICI 118587 a new ß-adrenoceptor partial agonist in man. Jpn Circ J 50: 636–643Google Scholar
- 31.Sato H, Inooe M, Matsyama T, Ozaki H, Shimazu T, Takeda H, Ishida Y, Kamada T (1987) Hemodynamic effects of the ß1-adrenoceptor partial agonist xamoterol in relation to plasma norepinephrine levels during exercise in patients with left ventricular dysfunction. Circulation 75: 213–220PubMedCrossRefGoogle Scholar
- 32.Starling EH (1920) On the circulatory changes associated with exercise. J R Army M Corps 34: 258–272Google Scholar