COMPARISON OF HEMODYNAMIC-EFFECTS AND PLASMA CYCLIC GUANOSINE-MONOPHOSPHATE OF NICORANDIL AND NITROGLYCERIN IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Hemodynamic tolerance has been observed within several hours of contin uous infusion of nitroglycerin (NTG). We examined the hemodynamic para meters as well as femoral arterial and venous cyclic guanosine monopho sphate (cGMP) concentrations during intravenous infusion of NTG or nic orandil, a nitrate and potassium channel opener, in patients with cong estive heart failure. Doses of NTG or nicorandil were titrated to achi eve a greater than or equal to 25% reduction in pulmonary capillary we dge pressure (PCWP) within 1 hour, and the infusion was maintained at a constant rate for 24 hours. The reduction in PCWP and mean arterial blood pressure was identical after a 1-hour infusion of either NTG or nicorandil. In the NTG group, PCWP and mean blood pressure were not si gnificantly different from the baseline value at 12 hours, but in tile nicorandil group PCWP and mean blood pressure remained significantly lower than the preinfusion value for 24 hours. The cGMP production wit h NTG (assessed by the difference between the plasma arterial and veno us cGMP level) paralleled the changes in PCWP, suggesting that the pla sma arteriovenous cGMP difference is a biochemical indicator of nitrat e tolerance. Although the sustained decrease in PCWP was observed in t he nicorandil group, cGMP production with nicorandil was also attenuat ed at 24 hours of continuous infusion. These findings suggest that the absence of the hemodynamic tolerance af nicorandil, a nitrate and pot assium channel opener, is likely due to its action os a potassium chan nel opener, and not to its nitrate activity.