[8-hour hemodynamic study of 2 sustained-release nitrate derivatives. Comparative double-blind study against placebo]

The aim of this study was to evaluate the duration of the hemodynamic effects of a new slow release preparation of isosorbide dinitrate and to compare its action with placebo and a slow release nitroglycerin preparation whose hemodynamic efficacity has already been demonstrated. The study was undertaken in 30 patients admitted to the intensive care unit during the acute phase of myocardial infarction complicated by left ventricular failure less than 12 hours after the onset of the chest pain. The patient population was uniform: 24 males, 6 females, mean age 61 years. Fifteen patients had anterior infarcts and 15 posterior infarcts. The drugs were administered double blind in a randomised fashion to 3 groups of 10 patients, the initial clinical and hemodynamic characteristics of which were comparable: 10 patients received placebo (placebo group); 10 patients received slow release nitroglycerin in a 7,5 mg gelule (NTG group) and 10 patients received 40 mg slow release isosorbide dinitrate (ISDN group). The following parameters were compared: heart rate, right atrial pressure, pulmonary artery and capillary pressures, systemic arterial pressure, cardiac index and systemic and pulmonary arterial resistances. These parameters were measured before therapy, half an hour, one hour and every two hours up to the 8th hour after drug administration. All patients were in moderate left ventricular failure with an initial mean capillary pressure of 18 mmHg +/- 1,3 mmHg. In the placebo group, none of the parameters studied changed significantly during the study. Pulmonary artery pressure fell significantly by 11 p. cent in the NTG group and 7,5 p. cent in the ISDN group. Mean pulmonary capillary pressure fell progressively in both treatment groups; the change was significant compared to the placebo group from the first hour for the ISDN group, and from the second hour for the NTG group. The fall remained significant at the 8th hour for the ISDN group but not in the NTG group. Cardiac index, systemic blood pressure, systemic and pulmonary arterial resistances did not change significantly. The cardiac index remained stable in the 30 patients, but with a number of individual variations depending on initial mean pulmonary capillary pressure and the importance of its fall after nitrate administration. The authors conclude that the hemodynamic effects of slow release NTG and ISDN in the acute phase of myocardial infarction complicated by moderate left ventricular failure are comparable. Pulmonary capillary pressure was the hemodynamic parameter which underwent the greatest variation in the two treatment groups. Its fall was more prolonged in the ISDN than in the NTG group.