[Dose and time dependence of hemodynamic tolerance development during intravenous nitrate therapy in acute myocardial infarct].

Intravenous nitroglycerin therapy during acute myocardial infarction has beneficial effects on infarct size, infarct complications, and mortality. Numerous dosage formulas for the continuous administration of nitrates are currently used, although several studies have demonstrated the rapid development of tolerance during long-term treatment in patients with ischemic heart disease. The dose and dosage of a continuous nitrate application in the clinical setting of acute myocardial infarction has thus yet to be resolved. This study investigated the hemodynamic effects of a 60-h, low- (33 micrograms/min) vs high- (133 micrograms/min) dose intravenous nitroglycerin (NTG) infusion in 16 patients with uncomplicated acute myocardial infarction. In group I (33 micrograms/min NTG; n = 8) the initial nitrate effect on the pulmonary capillary pressure (PCP-control: 14 +/- 1.5; 4 h: 7 +/- 0.9; 60 h: 7 +/- 0.8; mean +/- SEM; all values in mm Hg) and mean pulmonary artery pressure (PAPM-control: 23 +/- 2.3; 4 h: 15 +/- 1.3; 60 h: 14 +/- 1.3) remained unchanged for 60 h. In group II (133 micrograms/min NTG; n = 8) an almost complete loss of the initial effect on PCP (control: 15 +/- 1.6; 4 h: 5 +/- 1.4; 60 h: 12 +/- 1.3) and PAPM (control: 25 +/- 2.0; 4 h: 14 +/- 1.8; 60 h: 20 +/- 1.3) was observed. In contrast to high-dose application the low-dose NTG-infusion induced comparable acute hemodynamic effects that were not attenuated by tolerance development.