Influence of central inhibition of sympathetic nervous activity on myocardial metabolism in chronic heart failure: acute effects of the imidazoline I1-receptor agonist moxonidine.

Abstract

Although beta-adrenergic blockade is beneficial in heart failure, inhibition of central sympathetic outflow using moxonidine has been associated with increased mortality. In the present study, we studied the acute effects of the imidazoline-receptor agonist moxonidine on haemodynamics, NA (noradrenaline) kinetics and myocardial metabolism. Fifteen patients with CHF (chronic heart failure) were randomized to a single dose of 0.6 mg of sustained-release moxonidine or matching placebo. Haemodynamics, NA kinetics and myocardial metabolism were studied over a 2.5 h time period. There was a significant reduction in pulmonary and systemic arterial pressures, together with a decrease in cardiac index in the moxonidine group. Furthermore, there was a simultaneous reduction in systemic and cardiac net spillover of NA in the moxonidine group. Analysis of myocardial consumption of substrates in the moxonidine group showed a significant increase in non-esterified fatty acid consumption and a possible trend towards an increase in myocardial oxygen consumption compared with the placebo group (P=0.16). We conclude that a single dose of moxonidine (0.6 mg) in patients already treated with a beta-blocker reduced cardiac and overall sympathetic activity. The finding of increased lipid consumption without decreased myocardial oxygen consumption indicates a lack of positive effects on myocardial metabolism under these conditions. We suggest this might be a reason for the failure of moxonidine to prevent deaths in long-term studies in CHF.

• Authors: Reza Mobini, Michael Fu, Per-Anders Jansson, Claes-Håkan Bergh, Margareta Scharin Täng, Finn Waagstein, Bert Andersson
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 110 Issue 3 Pg. 329-36 (Mar 2006) ISSN: 0143-5221 [Print] England
• PMID: 16209659 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Antihypertensive Agents
• Fatty Acids, Nonesterified
• Imidazoles
• Imidazoline Receptors
• Receptors, Drug
• imidazoline I1 receptors
• moxonidine
• Norepinephrine

Topics

• Aged
• Antihypertensive Agents (pharmacology)
• Fatty Acids, Nonesterified (blood)
• Female
• Heart (drug effects)
• Heart Failure (metabolism, physiopathology)
• Hemodynamics (drug effects)
• Humans
• Imidazoles (pharmacology)
• Imidazoline Receptors
• Male
• Middle Aged
• Myocardium (metabolism)
• Norepinephrine (blood)
• Oxygen Consumption (drug effects)
• Receptors, Drug (agonists)
• Sympathetic Nervous System (drug effects, physiopathology)