Hemodynamic study of the development of tolerance in intravenous nitrate therapy

UNLABELLED: To investigate possible tolerance development under an intravenous treatment with nitrates, 22 patients with coronary artery disease were randomly assigned to receive either 4 mg/h of ISDN (n = 12) or placebo (n = 10) and were given additional 10 mg of ISDN or placebo after 23 h. Pulmonary artery pressures (PAP), cardiac output, and heart rate were registered before, and 4 h, 22.5 h, and 24 h after the beginning of treatment. At baseline both groups were similar with regard to pulmonary artery diastolic pressure (PADP) at rest and at comparable work load. Each patient of the placebo group showed identical PAPs at work. ISDN led to a 42-59% decrease of PADP at rest and 29-37% decrease at comparable work load. After 22.5 h a statistically insignificant reduction of ISDN effect was observed which could be reversed by additional ISDN p.o. A detailed analysis of the ISDN group showed seven patients with a persistently lowered PADP, (table; see text) whereas five patients demonstrated a partial diminuation of the ISDN effect. No patient showed a complete tolerance. In the placebo group blood pressure did not show any change during the treatment period (143 +/- 21/84 +/- 10 mmHg vs 137 +/- 17/79 +/- 10 mmHg), whereas ISDN infusion resulted in a continuously lowered blood pressure (150 +/- 22/83 +/- 11 mmHg vs 125 +/- 15/72 +/- 9 mmHg (p less than 0.001). Cardiac output and heart rate were similar under ISDN and placebo treatment. CONCLUSION: Continuous infusion of 4 mg of ISDN/h over 24 h and an additional dose of 10 mg of ISDN after 23 h provided a significant reduction in PADP, blood pressure and rate pressure product over 24 h at rest and during exercise.