The Effects of Trapidil on Left Ventricular Function and Platelet Aggregation in Patients with Coronary Artery Disease Subjected to Pacing

Abstract

The effects of the intravenous administration of 100 mg of trapidil on systolic and diastolic left ventricular functions and coronary sinus blood flow, as well as on myocardial lactate metabolism and platelet aggregation, were investigated before and after pacing in 12 patients with coronary artery disease. Pacing without administration of trapidil provoked angina in 6 of these patients. During rest, trapidil decreased the mean blood pressure by an average of 5 mmHg (from 112±15 to 107±8 mmHg, p<0.05) and the left ventricular end-diastolic pressure by an average of 4 mmHg (from 10±3 to 6±2 mmHg, p<0.05). Trapidil also caused both the max dp/dt and the coronary sinus blood flow to increase slightly, although it had no significant effect on diastolic function, myocardial lactate metabolism, or platelet aggregation. During the pacing that followed trapidil administration, chest pain was not provoked in the same 6 patients who had previously experienced chest pain on pacing. The extent of ST-segment depression also improved from -1.6±0.3 to -0.9±0.7 mm (p<0.05) and there was a significant suppression of the production of myocardial lactate. When pacing was terminated, trapidil caused a decrease in left ventricular systolic pressure from 173 to 156 mmHg (p<0.05), and also caused a decrease of the left ventricular end-diastolic pressure, from 16±4 to 8±2 mmHg (p<0.05). Trapidil had no significant effect on platelet aggregation activity with either a 1 μM or a 2 μM. dose of ADP (adenosine diphosphate). However, the beta-TG level was suppressed, decreasing from 119±14 to 99±19 ng/ml in the arterial blood (p<0.1) and from 114±9 to 103±17 ng/ml (p<0.1) in the coronary sinus blood. Reductions in the preload and afterload by trapidil were of far greater magnitude than either its coronary dilatory or positive chronotropic effects in patients with coronary artery disease. Thus trapidil, a new antianginal agent appears to inhibit the production of platelet derived growth factors and may, therefore, protect the arteries from atherosclerosis as it promotes beneficial systemic hemodynamics in patients with depressed ventricular function. © 1991, International Heart Journal Association. All rights reserved.