Effects of ondansetron on respiratory pattern and sensation of experimentally induced dyspnea.

CONTEXT Dyspnea remains a therapeutic challenge, especially in chronic respiratory conditions. Recent studies have shown that the induction of unpleasant dyspnea sensations activates areas in the insular cortex. OBJECTIVE This study was designed to investigate the potential effects of ondansetron, a potent anti-serotonin agent, on induced dyspnea sensation. TYPE OF STUDY A randomized double blind study. SETTING Pulmonary Function Laboratory of Hospital das Clínicas de Ribeirão Preto. PARTICIPANTS Ten healthy male volunteers (mean age +/- standard error = 23.1 +/- 0.41 years) without respiratory diseases and showing normal spirometric tests. INTERVENTIONS Uncomfortable breathing was induced in the volunteers on two different days, via the use of inspiratory resistors (loads of 0, 7, 14 and 21 cm H2O/l/sec) and breathholding, two hours after taking 8 mg of ondansetron (Ond) or placebo (Plac). MAIN MEASUREMENTS Respiratory discomfort during breathing under loading was evaluated on a 100-mm visual analog scale. The maximum length of time of voluntary apnea was measured in seconds. RESULTS The mean maximum voluntary apnea time did not differ between the ondansetron and placebo days (Plac = 96 +/- 6.6 sec vs. Ond = 100 +/- 7.9 sec). Ondansetron did not influence the dyspnea sensation induced by different inspiratory loads (0 cm H2O/l/sec: Ond = 1.4 mm +/- 0.44 vs. Plac = 2.1 +/- 0.85 mm; 7 cm H2O/l/sec: Ond = 16.6 +/- 2.74 mm vs. Plac = 13.7 +/- 2.06 mm; 14 cm H2O/l/sec; Ond = 30.5 +/- 4.50 mm vs. Plac = 27.1 +/- 3.44 mm; 21 cm H2O/l/sec: Ond = 50.3 +/- 6.72 mm vs. Plac = 49.4 +/- 6.72 mm). Ondansetron led to significant decreases in tidal volume under basal conditions and when breathing under the highest inspiratory loading (0 cm H2O/l/sec: Ond = 0.83 +/- 0.26 l vs. Plac = 1.0 +/- 0.28 l; 21 cm H2O/l/sec: Ond = 0.86 +/- 0.23 l vs. Plac = 1.1 +/- 0.22 l) CONCLUSION The present results suggest that 5-HT3 receptors do not play an important role in the mediation of dyspnea sensations.