EFFECT OF AMLODIPINE ON NOREPINEPHRINE KINETICS AND BAROREFLEX FUNCTION IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Background: The use of calcium channel blocking drugs is controversial in heart failure, partly because of concerns about neurohormonal stim ulation. preliminary data suggest that the newer agent amlodipine may be useful in this syndrome. Suppression of sympathetic activity either directly or by sensitized baroreflex function could be contributing f actors to the clinical use of this drug.Objective: To assess the effec t of short-term amlodipine therapy on baseline measures of sympathetic activity and baroreflex function in patients with chronic stable cong estive heart failure (CHF). Methods: seven patients with chronic CHF ( New York Heart Association functional class II or III, moderate to sev ere reduction in left ventricular systolic function) were studied. All patients underwent baroreflex testing with head-up tilt, head-down ti lt and head-down tilt with phenylephrine infusion. Heart rate, mean ar terial pressure, forearm blood flow and resistance, and plasma norepin ephrine (NE) kinetics were assessed at baseline and after each baroref lex perturbation on three occasions: a control test and after 10 days each of placebo and amlodipine therapy. Results: Plasma NE and NE spil lover did not significantly increase after amlodipine administration c ompared with control and placebo tests (488 +/- 119 pg/ml vs 350 +/- 8 5 and 325 +/- 87 pg/ml). In three subjects, plasma NE levels were esse ntially unchanged, whereas in four they rose markedly (289 +/- 87 pg/m l at control vs 551 +/- 158 pg/ml). There was no difference in the res ponse of any variable during baroreflex perturbations after amlodipine administration compared with control and placebo tests. One subject w ho tolerated head-down tilt coupled with phenylephrine administration during the control and placebo tests became markedly short of breath d uring the same intervention after amlodipine administration. plasma NE levels in this patient had risen markedly while receiving amlodipine and were not appropriately suppressed during the baroreflex loading ma neuver. Conclusions: Short-term therapy with amlodipine does not suppr ess sympathetic activity or alter efferent responses io baroreflex per turbation in patients with stable chronic CHF. Significant increases i n plasma NE and NE spillover and abnormal responses to baroreflex stim ulation are possible after administration of this drug. The relevance of these findings to studies in larger number of patients requires fur ther study.