Copyright © 1994 by the European Society of Cardiology.
© 1994 The European Society of Cardiology
The effects of intracoronary substance P and acetylcholine on coronary blood flow in patients with idiopathic dilated cardiomyopathy
National Heart and Lung Institute, and The Royal Brompton National Heart and Lung Hospital London, U.K
Received 17 February 1994; revised 27 May 1994; .
Correspondence: Diana R Holdright, The London Chest Hospital, Bonner Road, London E2 9JX, U.K.
Abstract
Attenuation of the increase in blood flow caused by acetylcholine in the peripheral vasculature and coronary circulation of patients with heart failure has been interpreted as an impairment of endothelium-dependent vasodilation. The aim of this study was to compare in man the effects of acetylcholine, which also has endothelium-independent actions, with substance P, which appears to be a pure endothelium-dependent vasodilator, on epicardial and resistance coronary arteries in patients with idiopathic dilated cardiomyopathy.
The effects of intracoronary acetylcholine (10–1M and 10–6M) and substance P (5, 10 and 25 pmol. min–1) on epicardial coronary artery diameter and coronary blood flow velocity were measured with an intracoronary Doppler flow probe and quantitative coronary angiography in 11 patients with idiopathic dilated cardiomyopathy and 10 control subjects.
Epicardial coronary artery diameter did not change with acetylcholine but increased significantly with substance P in both groups (cardiomyopathy patients: 3.3 ± 0.2 mm (mean ± SEM) at baseline vs 3.9 ± 0.2 mm with substance P 25 pmol. min–1, P<0.01, controls: 3.1± 0.2 mm at baseline vs 3.9 ± 0.3 mm with substance P 25 pmol. min–1, P<0.05). Coronary flow ratios with acetylcholine were lower in cardiomyopathy patients (10–7m: 1.4± 0.1 vs 2.3 ± 0.4, P=0.05; 10–6M: 1.8 ± 0.2 vs 3.2 ± 0.5, P=0.05 vs controls). Coronary flow ratios with substance P 5, 10 and 25 pmol. min–1 were 1.5 ± 0.1 vs 1.5± 0.1, l.8 ± 0.2 vs 2.2 ± 0.2 and 2.1 ±0.2 vs2.8 ± 0.3 (P=NS, cardiomyopathy patients vs controls respectively).
Whereas epicardial coronary artery responses to acetylcholine and substance P are similar in patients with dilated cardiomyopathy and control subjects, the actions of acetylcholine and substance P on coronary resistance vessels differ. The impairment with acetylcholine has several components, related either to muscarinic receptorltransduction mechanisms or the production of other vasoactive compounds, rather than a simple inability of the vascular endothelium to cause vasodilation.
Key Words: Dilated cardiomyopathy • endothelium derived relaxing factor • substance P acetylcholine • coronary blood flow
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