Plasma noradrenaline as an index of sympathetic tone in coronary arterial disease: the confounding influence of clearance of noradrenaline

Kinetics of [ 3H]noradrenaline in the plasma were compared with plasma noradrenaline concentration in assessing overall sympathetic activity in six groups totalling 118 subjects. Arterial plasma noradrenaline in 21 control subjects was 204 ± 14 pg/ml, similar to 20 patients with stable angina not treated with β-blockers (194 ± 25 pg/ml) and to 31 patients with stable angina treated with β-blockers (232 ± 19 pg/ml). Plasma noradrenaline was increased in 17 patients with unstable angina (366 ± 50 pg/ml, P < 0.01), in 14 patients with recent acute myocardial infarction (460 ± 44 pg/ml, P < 0.001) and in 15 patients with treated cardiac failure (582 ± 78 pg/ml, P < 0.001). Whole body clearance of noradrenaline from plasma was, however, reduced in each of the last three groups compared to controls by 20% ( P < 0.05), by 34% ( P < 0.01) and by 31% ( P < 0.01), respectively. In the 31 patients with stable angina on β-blockers, clearance of noradrenaline was also reduced by 20% ( P < 0.05). Whole body noradrenaline spillover, a potentially more accurate measure of overall sympathetic activity than concentration of noradrenaline in plasma, was 235 ± 20 ng min −1 m −2 in controls, was similar in subjects with stable angina (no β-blockers; 260 ± 34 ng min −1 m −2, β-blockers; 200 ± 17 ng min −1 m −2), but was increased in patients with unstable angina (310 ± 27 ng min −1 m −2, P < 0.05), with recent acute myocardial infarction (346 ± 40 ng min −1 m −2, P < 0.05) or with heart failure (438 ± 65 ng min −1 m −2, P < 0.01). Overall sympathetic activity is unchanged in stable angina, but is progressively increased in patients with unstable angina, recent myocardial infarction or heart failure. Plasma concentration of noradrenaline fails accurately to reflect this as a result of decreased clearance of noradrenaline in these patients. The results show the potential limitations of measurement of noradrenaline in the plasma as an index of overall sympathetic activity and the importance of assessing clearance.