COMBINED EFFECTS OF NITRATES ON THE CORONARY AND PERIPHERAL-CIRCULATION IN EXERCISE-INDUCED ISCHEMIA

We compared the effects of isosorbide dinitrate (ISDN) administered by intracoronary and intravenous routes in 10 patients with severe coronary artery disease, stable effort angina, and very low exercise tolerance. Supine bicycle ergometer exercise was performed under four conditions: 1) control, 2) after intracoronary administration of 0.4 mg ISDN, 3) 1 hour later (control 2), and 4) after administration of intravenous 4 mg ISDN. At rest, intracoronary ISDN caused no significant hemodynamic effects, whereas intravenous infusion of ISDN resulted in a decline in left ventricular (LV) systolic pressure (-20 ± 5 mm Hg), LV end-diastolic volume (-27 ± 3%), and LV end-systolic volume (-30 ± 4%). After intracoronary infusion of ISDN, ST segment depression and the increase in LV end-diastolic pressure and LV end-systolic volume induced by exercise were significantly less abnormal than during control (0.20 ± 0.09 vs. 0.14 ± 0.08 mV, 36 ± 7 vs. 24 ± 8 mm Hg, and 91 ± 40% vs. 40 ± 29%, respectively). When exercise was performed after intravenous infusion of ISDN, the above-mentioned parameters were significantly improved even further: ST segment depression to 0.05 ± 0.07 mV, end-diastolic pressure to 14 ± 7 mm Hg, and LV end-systolic volume to 5 ± 11% (all p < 0.01 compared with intracoronary ISDN). Thus, in patients with severe coronary artery disease, it is suggested that intracoronary nitrates increase coronary blood supply during effort-induced ischemia, based on significant improvements in the indirect measures of ST segment depression, LV end-diastolic pressure, and LV volume. More marked effects on these measures were observed after intravenous administration, when coronary and peripheral effects are combined.