Early tolerance to hemodynamic effects of high dose transdermal nitroglycerin in responders with severe chronic heart failure

Transdermal systems for delivery of nitroglycerin have been shown to provide sustained blood levels of the drug for at least 24 hours. Investigations of hemodynamic effects of transdermal nitroglycerin in patients with heart failure have demonstrated a transient reduction in pressure lasting less than the expected 24 hours. These findings could be due to the development of circulatory tolerance to the vasodilatory effects of nitroglycerin or to insufficient drug dosing. In the present study, we compared the hemodynamic effects of the first and the second doses of high dose (120 mg) transdermal nitroglycerin given 24 hours apart in 11 responders (greater than or equal to 20% reduction in mean pulmonary artery wedge pressure lasting greater than or equal to 2 hours). Initiation of nitroglycerin therapy resulted in a significant reduction in mean right atrial pressure lasting for 14 hours and in a reduction in mean pulmonary artery and mean pulmonary artery wedge pressures lasting 24 hours. After administration of the second dose, mean right atrial pressure at 2 hours (9 +/- 5 versus 7 +/- 4 mm Hg), 4 hours (8 +/- 5 versus 6 +/- 4 mm Hg) and 8 hours (8 +/- 5 versus 6 +/- 3 mm Hg) was higher than after the first dose (p less than 0.05). Both mean pulmonary artery and mean pulmonary artery wedge pressures were significantly higher after the second nitroglycerin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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