Norepinephrine kinetics and cardiac output during nonhypotensive lower body negative pressure

Recently we have shown that arterial norepinephrine (NE) concentration increases significantly during lower body negative pressure (LBNP) of -15 mmHg. Interestingly, the increase was found to be related predominantly to a decrease in arterial NE clearance. We postulated that this reduction in clearance would be related to a reduction in cardiac output. Accordingly, we measured both cardiac output (2-dimensional echocardiographic/Doppler technique) and arterial NE kinetics ([3H]NE continuous infusion radiotracer technique) during LBNP of -15 mmHg. These measures of cardiac output and arterial NE spillover and clearance were obtained in 12 normal subjects at baseline, 5 and 10 min (Early) and 25 and 30 min (Late) of LBNP. We found that arterial NE concentration increased significantly, by 25% Early and 22% Late (P = 0.001). Spillover, however, did not change (P = 0.258), whereas clearance decreased by 12% Early and 19% Late (P = 0.014), and cardiac output decreased by 15% Early and 19% Late (P = 0.001). These reductions in clearance and cardiac output correlated significantly (r = 0.61, P = 0.001). No correlation was noted between spillover and cardiac output (r = 0.027, P = 0.874). We conclude that the increases in arterial NE concentration during nonhypotensive LBNP are predominantly due to decreased cardiac output with resultant decreases in systemic clearance of NE. These findings suggest that the ability to clear NE from the circulation is linked to the level of cardiac output and that low cardiac output states by themselves may lead to an elevation in arterial plasma NE concentrations.