PROGRESSION OF LEFT-VENTRICULAR DYSFUNCTION SECONDARY TO CORONARY-ARTERY DISEASE, SUSTAINED NEUROHORMONAL ACTIVATION AND EFFECTS OF IBOPAMINE THERAPY DURING LONG-TERM THERAPY WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR

Left ventricular function and neurohormonal status in patients with he art failure remaining symptomatic during therapy with angiotensin-conv erting enzyme inhibitors were assessed, and the effects of dopaminergi c receptor stimulation in this setting were determined. Neurohormonal and left ventricular function (radionuclide angiography) data were obt ained in 19 patients with symptomatic ischemic heart failure. Measurem ents were repeated after 4 to 6 weeks of therapy with the dopamine ago nist ibopamine (100 mg, 3 times/day) or placebo administered in a doub le-blind, randomized, parallel group design. At baseline, despite ther apy with enalapril, the angiotensin II levels (mean 39.4 pg/ml; p <0.0 1 vs controls) were significantly increased, as were plasma norepineph rine (497 +/- 240 pg/ml; p <0.01 vs controls), endothelin-l, atrial na triuretic pop tide and arginine vasopressin. Moreover, in comparison w ith pretreatment values, left ventricular ejection fraction had decrea sed substantially (-9.1%) in patients with plasma norepinephrine great er than or equal to 600 pp/ml, but not in those with sower values of n orepinephrine. With ibopamine, plasma norepinephrine decreased from 51 6 +/- 241 to 391 +/- 208 pg/ml (n = 8; p <0.025 vs placebo), whereas i t increased with placebo. In conclusion, the neurohormonal control pro vided by an angiotensin-converting enzyme inhibitor is reduced in a la rge subset of patients during prolonged therapy; ibopamine appears to be a potentially useful drug to improve neurohormonal control in this setting.