Effects of an inhaled β2-agonist on cardiovascular function and sympathetic activity in healthy subjects

Abstract

Study objective: To determine the effect of a short-acting, inhaled β(2)-adrenergic receptor agonist, albuterol sulfate, administered by nebulization, on cardiovascular function and sympathetic activity in healthy individuals.

Design: Prospective, placebo-controlled, single-blind, crossover study.

Setting: University research center.

Subjects: Seventeen healthy subjects.

Intervention: After a screening visit to rule out cardiovascular abnormalities and anemia, each subject participated in two more separate visits. At the second visit, they were administered a single dose of either nebulized albuterol sulfate 2.5 mg diluted in 3 ml of normal saline or placebo (3 ml of normal saline). One week later, subjects returned for their third visit and received the other treatment.

Measurements and main results: At the two study visits, before and 30, 60, and 90 minutes after administration of albuterol or placebo, we measured plasma catecholamine levels (epinephrine and norepinephrine), cardiac output, heart rate, and systolic and diastolic blood pressure, and we calculated stroke volume, mean arterial pressure, and systemic vascular resistance (SVR). Inhaled placebo resulted in no significant change overall in any of the measured or calculated cardiovascular parameters. Compared with baseline values, albuterol administration after 30, 60, and 90 minutes, increased cardiac output (mean ± SD 4.2 ± 1.1, 4.4 ± 1.3, and 4.3 ± 1.1 L/min, respectively, vs 3.6 ± 1.0 L/min) and stroke volume (51 ± 15, 56 ± 14, and 56 ± 13 ml, respectively, vs 46 ± 12 ml), did not significantly change blood pressure, and decreased SVR (1401 ± 432, 1393 ± 424, and 1384 ± 391 dynes•sec/cm(5), respectively, vs 1661 ± 453 dynes•sec/cm(5)) (p<0.05 for all comparisons). Heart rate was significantly changed with both albuterol and placebo, but only at 30 minutes after treatment. Albuterol, but not placebo, also increased plasma norepinephrine levels.

Conclusion: In these healthy subjects, administration of a nebulized β(2)-agonist resulted in enhanced ventricular function and a decrease in SVR, suggesting peripheral vasodilation. In addition, the increase in norepinephrine level with albuterol, but not placebo, may have important implications in patients with known cardiovascular disease.