The hemodynamic, hormonal and
electrolyte effects of
prenalterol, a synthetic selective beta 1 agonist, were studied in six patients with New York Heart Association functional class II and III
heart failure.
Prenalterol was infused incrementally at 60, 120 and 240 nmol/min, each rate for 24 hours, producing steady-state plasma
prenalterol levels of 52 +/- 3, 121 +/- 6 and 194 +/- 9 nmol/1, respectively (mean +/- SEM). Hemodynamic and hormonal measurements were performed before, during and after
prenalterol administration under conditions of constant body posture and a regulated intake of
dietary sodium and
potassium.
Prenalterol induced a statistically significant increase in cardiac index (from 2.6 +/- 0.2 to 3.1 +/- 0.3 1/min/m2), with parallel increases in
stroke index (from 28 +/- 2 to 34 +/- 2 ml/beat/m2). Forearm blood flow measurements increased (from 2.9 +/- 0.5 to 4.1 +/- 0.6 ml/min/100 g), while calculated systemic vascular resistance fell, as did pulmonary capillary wedge pressure (from 13.7 +/- 1.6 to 10.5 +/- 1.7 mm Hg). The
drug did not alter heart rate, arterial pressure, right heart pressures or the frequency of ventricular
premature beats.
Prenalterol increased plasma
renin activity (from 2.9 +/- 0.8 to 6.6 +/- 1.8 nmol/1/hour),
angiotensin II (from 59 +/- 12 to 89 +/- 22 pmol/1), urinary
aldosterone excretion (from 41 +/- 10 to 78 +/- 34 nmol/day) and plasma
insulin (from 10.6 +/- 2.2 to 19.8 +/- 3.9 mU/1). Circulating
catecholamines,
cortisol,
glucose,
glucagon or
pancreatic polypeptide did not change. Dose-response studies in five patients showed dose-dependent increments in hemodynamic variables, while hormonal changes plateaued at the second dose level. We conclude that
prenalterol infusion augments myocardial contractility, reduces systemic vascular resistance, and stimulates
insulin release and the renin-angiotensin-aldosterone system.