Cardiovascular Effects of Selective I(f)-Channel Blockade

The study compares three treatment modalities in a human model of Postural orthostatic tachycardia syndrome (POTS): beta-blockers, I(f)-blockers, and placebo.

Elevated heart rate may lead to cardiac disease in the long-term. Therefore, drugs lowering heart rate are useful. Beta-blockers are an established treatment modality. They not only lower heart rate but also contractility, which might be undesirable in certain tachycardic disorders. Postural orthostatic tachycardia syndrome (POTS) patients complain about dizziness, weakness, headache, lightheadedness, fatigue, nausea, and presyncope. In some patients there is elevated heart rate even during supine rest. In POTS patients it is preferable to lower heart rate without reducing cardiac contractility which can be achieved by using so-called I(f)-blockers. Thus, they might be superior to beta-blockers in POTS. In our study, we artificially generate POTS in healthy male subjects for about 48 hours. We want to compare the cardiovascular effects and orthostatic tolerance of the following treatments: beta-blocker, I(f)-blocker, and placebo. Moreover, we will quantify changes in cardiovascular autonomic regulation brought about by I(f)-blockade versus placebo.

Sub-study 'Orthostatic tolerance': Change in heart rate after 20 mins of passive orthostasis. Sub-study 'Sympathetic system': arterial pressure related heart rate

Inclusion Criteria: healthy male age 18-40 years BMI: 18-30 kg/m² arterial blood pressure <=160/100 mm Hg co-operativity voluntariness Exclusion Criteria: conditions in which treatment might be ineffective or insecure co-medication within the last 4 weeks participation in another clinical trial within the last 4 weeks unability to understand the study's aim drug or alcohol abuse secondary hypertension creatinine > 130 μM (1.47 mg/dl) GOT/GPT > 2 times normal GGT > 3 times normal contraindications against reboxetine, beta-blocker, ivabradine asthma, psoriasis diabetes heart failure (NYHA III or IV) coronary artery disease peripheral occlusive disease cerebrovascular disease ventricular extrasystoles (Lown III-V) atrial fibrillation resting heart rate <60/min neurologic/psychiatric disorder pulmonary hypertension dysthyroid metabolism

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