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

We compared isosorbidedinitrate (ISDN) and 3-morpholinosydnonimine (SIN-1) as dilators of epicardial coronary arteries and inhibitors of ex vivo platelet aggregation in 23 patients referred for diagnostic coronary arteriography. After completion of the diagnostic study, the patient 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 arteries were assessed by quantitative digital coronary arteriography before and 5 min after each infusion was started. SIN-1 required an infusion rate of 1.0 mu g/kg/min to cause dilatation of proximal and middle segments of LAD and RCX. The highest infusion rate caused a modest decrease 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 thromboxane 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 that platelets of SIN-1-treated patients were slightly less sensitive to both stimuli as compared with platelets of ISDN-treated subjects. These ex vivo results suggest that SIN-1 may be superior to ISDN as an inhibitor of platelet activation.