Hemodynamic effects of isosorbide-5-mononitrate (TY-10368) on exercise-induced angina pectoris.

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To investigate the hemodynamic effects of isosorbide-5-mononitrate (ISMN), 11 patients with effort angina pectoris were studied.<BR>Hemodynamic and echocardiographic measurements were observed at rest and during angina-limited supine multi-stage bicycle ergometer exercise testings before and 120 min after oral administration of 20 mg of ISMN. Compared with the control exercise test, the mean ST-segment at peak exercise showed less depression after ISMN (P<0.001). At rest there were significant decreases in systolic and diastolic blood pressures after ISMN (P<0.001 and P<0.05, respectively). Both at rest and peak exercise there were significant decreases in pulmonary capillary wedge pressure (both P<0.0001), left atrial volume (both P<0.001), and left ventricular end-diastolic volume (both P<0.05), while cardiac index, pressure-rate-product, and systemic vascular resistance remained unchanged. The average peak value for plasma ISMN concentration was 460 ng/ml at 90 min after dosing, and the elimination half-life was 7 hours.<BR>These data would indicate that the antianginal effects of ISMN, which is appropriate for its prolonged duration of action, are mainly related to diminishment of myocardial oxygen requirements due to left ventricular preload reduction as a common mechanism.