Arterial-venous nitroglycerin gradient during intravenous infusion in man

We assessed the concentration of nitroglycerin (GTN) measured in plasma at different sampling sites in the circulation during a constant i.v. infusion. Twenty patients with chronic congestive cardiac failure underwent hemodynamic monitoring during i.v. GTN infusion. Our end point was a reduction in pulmonary capillary wedge pressure by at least 25% of its control value or a 10-fold increment over the initial infusion rate. Nitroglycerin infusion produced no change in heart rate, a reduction in mean arterial pressure from 90 +/- 21 (+/- SD) to 83 +/- 17 mm Hg (p less than 0.001), a fall in total peripheral resistance from 24.3 +/- 10.8 to 20.8 +/- 7.0 units (p less than 0.02), and a substantial reduction in both pulmonary capillary wedge pressure (from 27 +/- 6 to 20 +/- 6 mm Hg, p less than 0.001) and right atrial pressure (from 12 +/- 4 to 8 +/- 4 mm Hg, p less than 0.001). The concentrations of GTN in the pulmonary artery and systemic artery were similar (29.8 ng/ml +/- 52.8 and 25.1 +/- 48.4 ng/ml, respectively) and considerably higher than the concentration in the peripheral vein (7.3 +/- 15.4 ng/ml). There was a 17.4 +/- 19.1% extraction of GTN across the pulmonary vascular bed and a 60.8 +/- 27.2% extraction across the arterial-venous bed (p less than 0.001). There was no relationship between the arterial-venous extraction and the magnitude of arterial plasma (GTN concentration, the duration of the infusion of GTN or the total dose administered. These data show that a better understanding of GTN pharmacokinetics is provided by simultaneous arterial and venous samples.