Early hemodynamic effects at rest with acute and chronic isosorbide dinitrate treatment in patients with ischemic heart disease.

Asymmetric dosage regimens are used to circumvent development of nitrate tolerance and are believed to restore totally the hemodynamic responsiveness to an acute dosage of nitrates. This study assessed invasively the hemodynamics during supine rest before and for 50 min after peroral 30 mg isosorbide dinitrate (ISDN) in 16 patients with stable ischemic heart disease; 8 previously untreated patients (NT group) and 8 patients treated asymmetrically b.i.d. with 30 mg ISDN for 14 days prior to the invasive investigation (T group). Before initiation of treatment, both groups had identical mean arterial pressure (MAP) and heart rate (HR). On the day of invasive investigation, before intake of ISDN, MAP was higher in the T group but unchanged in the NT group. After the intake of ISDN, right atrial pressure (RAP), mean pulmonary arterial pressure, and pulmonary arterial wedge pressure declined markedly within 10 to 15 min in both groups, while MAP showed a more protracted decline, reaching a new level only after 25 to 30 min. In the NT group, HR accelerated markedly and remained elevated throughout the observation period, whereas in the T group HR showed no significant alteration after ISDN intake. At the end of the observation period, the cardiac index (CI) was definitely reduced in the NT group, but remained unchanged in the T group, while the systemic vascular resistance index was unchanged in the former and was clearly reduced in the latter. It is concluded that the fall in MAP in the NT group was solely due to a fall in CI, and that the decline in RAP and venous return in the NT group induced neurohumoral reflexes leading to a rise in HR and prevention of arterial dilation, whereas in the T group, already influenced by chronic treatment, such acute counterregulatory responses were markedly attenuated or absent.