Cardiovascular effects of nicorandil and nitroprusside in furosemide plus digoxin pretreated dogs

Abstract

AbstractIn support of human congestive heart failure (CHF) trials, the cardiovascular effects of the vasodilators nicorandil (NIC) and nitroprusside (NP) were examined in anesthetized and conscious dogs pretreated with the diuretic furosemide (FURO) and the cardiac glycoside digoxin (DIG). In anesthetized control dogs, iv NP (2–19 μg/kg/min) and NIC (24–105 μg/kg/min) maximally reduced mean arterial pressure (MAP) by 43 and 40 mmHg, respectively, with moderate increases in heart rate (HR). These hypotensive responses to NP and NIC were unmodified by iv FURO (2.65 mg/kg) + DIG (0.075 mg/kg) pretreatment (PT). FURO + DIG reduced central venous pressure (CVP) BY 3 mmHg, masking the separate effects of NP and NIC. In a third group, FURO's fluid volume depletion and DIG's plasma concentrations were unaffected by adjunctive NIC infused for 2.5 h at a mean 17 μg/kg/min iv. No untoward interactions were seen with any combination. In conscious dogs, the hypotension and tachycardia seen with iv NP (2–20 μg/kg/min) and NIC (20–160 μg/kg/min) were also unchanged after 5 days of oral FURO (5 mg/kg/day) and DIG (0.0125 mg/kg/day), with no intolerance. Repeated oral NIC (7.5 mg/kg/day × 3 days) in these chronic FURO + DIG dogs ws consistently hypotensive but steadily more tachycardiac. This study offers a prototype of 3‐way CHF drug interaction, demonstrates that NIC and NP can be safely combined with acute and chronic FURO and DIG, and shows that these CHF agents minimally affect the cardiovascular responses to NIC and NP in dogs.