Rapid disappearance of nitroglycerin following incubation with human blood

Abstract

Nitroglycerin (GTN) (at a concentration of 50 ng/mL) was incubated aerobically at 37 °C with whole blood, resuspended cells, and plasma from five normal volunteers. At several time periods following the initiation of the incubation (0, 1.5, 3, 5, 10, and 20 min for blood and resuspended cells, and 0, 30, 45, 60, 120, and 180 min for plasma) the samples were assayed for GTN in the incubation medium. Linear regression analyses were performed between the logarithm of the percentage GTN remaining and incubation time in order to determine the rate of disappearance of GTN from each system. A short t_1/2 for GTN was found in blood (6.2 min) and resuspended red cells (6.6 min) whereas a longer t_1/2 of 53.4 min was determined in plasma. These data indicate that the metabolism of GTN in human blood is rapid and predominantly localized in the cellular compartment of the blood. It is concluded that (a) the short circulatory t_1/2 of GTN following clinical administration is explained, at least in part, by rapid metabolism in blood and (b) it is necessary to rapidly centrifuge blood from GTN-treated patients and to freeze the plasma in order to prevent the breakdown of GTN prior to analysis.