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European Heart Journal 1999 20(23):1717-1723; doi:10.1053/euhj.1999.1710
Copyright © 1999 by the European Society of Cardiology.
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Differential anti-ischaemic effects of muscarinic receptor blockade in patients with obstructive coronary artery disease. Impaired vs normal left ventricular function

A.F.M Van Den Heuvela,b,f1, D.J Van Veldhuisenb, G.L Bartelsb, M Van Der Enta and W.J Remmea

a Sticares Research Foundation, Rotterdam, The Netherlands
b Department of Cardiology/Thoraxcenter, University Hospital Groningen, Groningen, The Netherlands

revised April 27, 1999; accepted April 28, 1999

Abstract

Aims In patients with coronary artery disease acetylcholine (a muscarinic agonist) causes vasoconstriction. The effect of atropine (a muscarinic antagonist) on coronary vasotone in patients with normal or impaired left ventricular function is unknown.

Methods and Results Twenty-four patients who required atropine infusion (to supplement heart rate response) during atrial pacing (pacing was conducted to assess ischaemia as part of an experimental protocol) were studied; 17 patients had normal and seven impaired left ventricular function (ejection fraction ≤0·40). Two control groups were selected from a large database (from patients in whom atrial pacing was carried out but to whom atropine was not administered) to match the normal (n=20) and dysfunction (n=10) groups. In the normal left ventricular function group atropine increased rate pressure product by 12±4%, as compared to those without atropine (P<0·05). Left ventricular end diastolic pressure increased less in the atropine group (+40±8% vs +78±6%;P<0·05). Arterial norepinephrine increased similarly in both groups, but coronary flow (as assessed by using a thermodiluting method in the coronary sinus) increased 23±4% more in the atropine group (P<0·05). Further, there were lower levels of myocardial lactate production and ST-segment depression in the atropine group [lactate extraction +13±6% (atropine) vs –19±4% (controls), ST-segment depression 1·3±0·6 (atropine) vs 1·8±0·2mm (control), both P<0·05 between groups]. In contrast, in the dysfunction group the overall effect of atropine was less pronounced.

Conclusion In patients with normal left ventricular function atropine improves coronary flow and reduces myocardial lactate production and ST-segment depression during atrial pacing, suggesting a reduction in myocardial ischaemia.

Key Words: Coronary disease, endothelial functionischaemia, muscarinic antagonists

f1 Correspondence: Dr A.F.M. van den Heuvel, Dept. of Cardiology/Thoraxcenter, University Hospital Groningen, P.O. ox 30.001, 9700 RB Groningen, The Netherlands.

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This Article
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