ISOSORBIDEDINITRATE AND SIN-1 AS DILATORS OF HUMAN CORONARY-ARTERIES AND PLATELET INHIBITORS

We compared isosorbidedinitrate (ISDN) and 3-morpholinosydnonimine (SI N-1) as dilators of epicardial coronary arteries and inhibitors of ex vivo platelet aggregation in 23 patients referred for diagnostic coron ary arteriography. After completion of the diagnostic study, the patie nt received graded intravenous (i.v.) infusions (0.5, 1.0, and 1.5 mu g/kg/min) of either SIN-1 (n = 11) or ISDN (n = 12). Diameters of left anterior descending (LAD) and left ramus circumflex (RCX) coronary ar teries were assessed by quantitative digital coronary arteriography be fore and 5 min after each infusion was started. SIN-1 required an infu sion rate of 1.0 mu g/kg/min to cause dilatation of proximal and middl e segments of LAD and RCX. The highest infusion rate caused a modest d ecrease in mean arterial blood pressure (MAP). In these aspects, SIN-1 was equivalent to ISDN. In addition, blood was collected immediately before treatment and after infusion of the highest dose of ISDN or SIN -1. The sensitivity of platelet-rich plasma (PRP) to ADP and the throm boxane A(2) (TXA(2)) mimetic U-46619 was determined in an aggregometer . The lesser responses to threshold concentrations of ADP and U-46619 and the slight shift in both concentration-response curves indicated t hat platelets of SIN-1-treated patients were slightly less sensitive t o both stimuli as compared with platelets of ISDN-treated subjects. Th ese ex vivo results suggest that SIN-1 may be superior to ISDN as an i nhibitor of platelet activation.