Beschreibung:
<jats:sec><jats:title>Background</jats:title><jats:p>Postural tachycardia syndrome (POTS) patients show excessive cardiac sympathetic drive with standing. The pacemaker current I(f) mediates sympathetic influences on heart rate.</jats:p></jats:sec><jats:sec><jats:title>Hypothesis</jats:title><jats:p>Pharmacological I(f) inhibition with ivabradine improves upright tachycardia in a human pharmacological POTS model.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In a double‐blind, randomized, three‐way crossover study, 21 healthy men ingested the selective norepinephrine transporter inhibitor reboxetine 8 mg to raise cardiac sympathetic drive and in addition placebo, 7.5 mg ivabradine, or 95 mg metoprolol (positive control) on separate days. We applied 60° head‐up tilt for 20 minutes followed by additional lower body negative pressure.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Resting heart rate was 67±11 bpm with placebo, 65±12 bpm with ivabradine, and 59±7 bpm with metoprolol. During head‐up tilt, heart rate increased 53±17 bpm with placebo. Compared with placebo, ivabradine and metoprolol reduced upright heart rate by 12 (95% CI 4–21, p<.006) and 21 (95% CI 13–30, p<.0001) bpm, respectively. Orthostatic tolerance was not affected by either treatment.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The cardiac hyperadrenergic state induced by pharmacological norepinephrine transporter inhibition is a useful model for human pharmacological research. Using this model, we showed that I(f) inhibition ameliorates hyperadrenergic orthostatic tachycardia. <jats:bold>Funded by Deutsche Forschungsgemeinschaft.</jats:bold></jats:p></jats:sec>