Effects of A 1 Adenosine Receptor Agonism Using N 6 -Cyclohexyl-2′- O -Methyladenosine in Patients With Left Ventricular Dysfunction

Abstract

Background The role of adenosine as a neuromodulator in heart failure was studied with the use of a selective adenosine A 1 receptor agonist, N 6 -cyclohexyl-2′- O -methyladenosine (SDZ-WAG 994). Methods and Results Fifty patients with heart failure symptoms and moderate left ventricular systolic dysfunction had a balloon flotation catheter inserted. Patients received placebo or a single oral dose of either 1, 2, or 5 mg SDZ-WAG 994. After baseline measurements were obtained, hemodynamic and electrophysiological recordings were repeated at 30-minute intervals for the next 4 hours, then every 6 hours for the next 24 hours. Blood samples for norepinephrine, epinephrine, aldosterone, atrial natriuretic peptide, and plasma renin activity were drawn at baseline and 2 hours after drug administration. A 1 adenosine receptor agonism produced no important effects on systemic, right atrial, pulmonary artery, or pulmonary capillary wedge pressures; cardiac index; respiratory rate; or heart rate. The PR interval (a reflection of A 1 receptor–mediated activity) increased significantly in a stepwise fashion. At the 5-mg dose of SDZ-WAG 994, significant increases in atrial natriuretic peptide (216±137 to 407±146 pg/mL) and norepinephrine (477±243 to 618±237 pg/mL) levels were noted. Conclusions A 1 adenosine receptor agonism with SDZ-WAG 994 resulted in no significant hemodynamic changes at rest in this subset of patients with left ventricular dysfunction. An increase in the PR interval and atrial natriuretic peptide level, consistent with adenosine A 1 receptor–mediated activity, was observed. In addition, an increase in the norepinephrine level was observed, suggesting a role for adenosine as a peripheral nervous system neuromodulator.