EARLY HEMODYNAMIC-EFFECTS AT REST WITH ACUTE AND CHRONIC ISOSORBIDE DINITRATE TREATMENT IN PATIENTS WITH ISCHEMIC-HEART-DISEASE

A symmetric dosage regimens are used to circumvent development of nitr ate tolerance and are believed to restore totally the hemodynamic resp onsiveness to an acute dosage of nitrates. This study assessed invasiv ely the hemodynamics during supine rest before and for 50 min after pe roral 30 mg isosorbide dinitrate (ISDN) in 16 patients with stable isc hemic heart disease; 8 previously untreated patients (NT group) and 8 patients treated asymmetrically b.i.d. with 30 mg ISDN for 14 days pri or to the invasive investigation (T group). Before initiation of treat ment, both groups had identical mean arterial pressure (MAP) and heart rate (HR). On the day of invasive investigation, before intake of ISD N, MAP was higher in the T group but unchanged in the NT group. After the intake of ISDN, right atrial pressure (RAP), mean pulmonary arteri al pressure, and pulmonary arterial wedge pressure declined markedly w ithin 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 observa tion period, whereas in the T group HR showed no significant alteratio n after ISDN intake. At the end of the observation period, the cardiac index (CT) was definitely reduced in the NT group, but remained uncha nged in the T group, while the systemic vascular resistance index was unchanged in the former and was clearly reduced in the latter. It is c oncluded 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 o f arterial dilation, whereas in the T group, already influenced by chr onic treatment, such acute counterregulatory responses were markedly a ttenuated or absent.