EFFECTS OF LOW-DOSES OF DOPAMINE ON HEMOD YNAMICS, PLASMA-CATECHOLAMINES, ALPHA-2 AND BETA-2 RECEPTORS IN PATIENTS WITH HEART-FAILURE

Twelve patients with dilated cardiomyopathy in NYHA class III-IV were infused with low doses of dopamine of 3 mug/kg BW/min and 6 mug/kg BW/ min over 24 h, respectively, to investigate the therapeutic effects on hemodynamics, urinary excretion, plasma levels of epinephrine, norepi nephrine and dopamine, and on alpha2 and beta2 receptor density. At a dose of 3 mug/kg BW/min (dopamine plasma levels: 12.6-13.9 ng/ml), car diac output (CO) was found increased from 4.3 +/- 3.6 to 5.2 +/- 2 l/m in already 4 h after starting the infusion (p < 0.05) and remained at this level beyond 24 h (5.0 +/- 1.1 I/min). Mean pulmonary capillary a nd pulmonary artery pressure decreased from 18 +/- 6 and 26 +/- 10 aft er 4 h to 11 +/- 4 (p < 0.05) and 19 +/- 7 mmHg (p < 0.05), respective ly. This decrease persisted through 24 h (12 +/- 4 and 19 +/- 7 mmHg, respectively; p < 0.05). Within these 24 h, beta2 receptor density inc reased from 679 +/- 105 to 777 +/- 84 binding sites/cell (p < 0.05), w hile a, receptor density decreased from 307 +/- 105 to 270 +/- 121 fmo l/mg protein (p < 0.05). There was, however, no significant alteration in either heart rate, systolic, diastolic, or mean aortic pressure. I ncreasing the dose of dopamine to 6 mug/kg BW/min (dopamine plasma lev els: 15.4-17.4 ng/nil) resulted in an only temporary elevation of CO ( 4 8 h), with subsequent decrease of CO to initial values of 4.0 l/min despite continued dopamine infusion, as a consequence of tolerance dev elopment. Systemic and pulmonary pressures showed no significant alter ations. Alpha2 receptor density continued to decrease significantly to 234 fmol/mg protein (p < 0.05) after 4 h of dopamine infusion (6 mug/ kg/min). The present investigation underlines the favorable hemodynami c and neurohumoral effects of low-dose dopamine up to 32 h after start ing dopamine infusion in patients with chronic heart failure. At infus ion beyond this period of time, even at increased doses, tolerance is expected to develop.