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Arginine

Licorice

Subjects with primary or secondary hypertension and normotensive control subjects. In addition haemodynamic recordings to 50 subjects suffering from chronic fatigue syndrome will be performed.

Subjects who had voluntarily decided to participate in a professionally coached marathon school (Varala Sports Institute, Tampere) were given the chance for haemodynamic recordings before, during and after the training protocol.

Normotensive subjects, daily liquorice ingestion (daily glycyrrhizin dose 290-370 mg) for 2 weeks, haemodynamic measurements before and after the intervention.

Daily ingestion of yoghurt containing small milk casein-derived polypeptides for 12 weeks versus placebo yoghurt.

Hypertensive subjects, bisoprolol 5 mg once daily versus placebo in a double-blind, cross-over protocol.

Subjects with aortic stenosis confirmed by echocardiography

35 normotensive subjects who received research drugs (nitroglycerin, salbutamol, placebo resoriblet, placebo inhalation, L-arginine infusion, saline infusion) in a placebo-controlled, double-blinded manner

Altogether 80 athletes participating in a full length Ironman competition. Non-invasive recordingds are performed under normal conditions during the training period and after completion of a full-length Ironman competition.

From the beginning of the study until the end of year 2016 a single dose of sublingual nitroglycerin was given to examine the associated acute haemodynamic effects (recordings completed).

Nitroglycerin 0.25 mg (single dose, no longer given since January 2017)

From the beginning of the study until the end of year 2016 a 400 µg dose of inhaled salbutamol was given to examine the associated acute haemodynamic effects (recordings completed).

Salbutamol 400 µg (single dose, no longer given since January 2017)

From the beginning of the study until the end of year 2016 L-arginine infusion 10 mg/kg/min could be given for 10 minutes to examine acute haemodynamic effects (recordings completed).

L-arginine (10 min infusion, no longer given since January 2017)

Daily liquorice intake (daily glycyrrhizin dose 290-370 mg) for two weeks, measurements before and after intervention (recordings completed).

Liquorice (2 weeks, glycyrrhizin 290-370 mg daily, no longer given since 2012)

Daily intake of yoghurt containing small milk casein-derived polypeptides (12 weeks) and placebo yoghurt (12 weeks), measurements before and after intervention (recordings completed 2011).

Small milk casein-derived polypeptides (12 weeks daily, recordings completed 2011)

Bisoprolol 5 mg daily for 3 weeks and placebo tablet daily for 3 weeks, double-blind, randomized, placebo-controlled cross-over protocol. Measurements before and after interventions (recordings completed 2011).

Bisoprolol (5 mg daily for 3 weeks, recordings completed 2011)

Ilkka H Pörsti, MD, PhD, Professor

Elina J Hautaniemi, PhD

Ilkka Pörsti, Professor

Ilkka H Pörsti, Professor

Ilkka Pörsti, MD, PhD, Professor

Ilkka Pörsti, MD, PhD

The primary aim of the present study was to examine the haemodynamic changes in primary hypertension and secondary hypertension (renal diseases, endocrine diseases, obesity-associated hypertension) with a non-invasive haemodynamic measurement protocol utilizing radial pulse wave analysis and whole-body impedance cardiography in both supine position and during head-up tilt. For comparison, haemodynamics of subjects with chronic fatigue syndrome will also be recorded.

Elevated blood pressure (BP) and related cardiovascular complications are the leading causes of morbidity and mortality in the modern world. In routine clinical practice, the haemodynamic status is commonly assessed by measuring heart rate and blood pressure at rest, which provides only limited information about functional haemodynamic status. In addition, the haemodynamic changes resulting in similar elevations of BP may differ substantially between patients and disorders.

Therefore, we investigated the haemodynamic changes in primary and secondary hypertension and in the control subjects with non-invasive radial pulse wave analysis and whole-body impedance cardiography. The method includes the determination of volume status using bioimpedance spectroscopy, determination of peripheral and central BP, cardiac function, vascular resistance, arterial compliance and indices of pulse wave reflection. Besides the measurements performed in the supine position, passive orthostatic challenge is included in the protocol to assess the upright functional haemodynamic status.

The repeatability and reproducibility of the protocol was first examined with a double-blind, randomized protocol in 35 subjects (methodological study group), and after that the administration of research drugs has been open-label. The effects of single doses of two largely endothelium-dependent agents, inhaled salbutamol and intravenous L-arginine, and one endothelium-independent agent, sublingual nitroglycerin, were investigated. However, challenges with the acute dosing of all medical compounds was terminated at the end of December 2016. Thereafter, the measurement protocol has included supine and upright recordings on the tilt-table, followed by supine measurements during paced breathing (15 breaths per minute for 5 minutes, 6 breaths per minute for 5 minutes) that modulate the autonomic nervous tone.

The study population has consisted of subgroups described below. The study protocol of each subgroup has been approved by the ethics committee of the Pirkanmaa Hospital District (Ethics committee ID's above), and the administration of research drugs has also been approved by the Finnish Agency for Medicines (EudraCT-numbers above).

HaemoDYNAMICs in Primary and Secondary Hypertension

Non-Invasive HaemoDYNAMICs in Primary and Secondary Hypertension: the DYNAMIC-study

Haemodynamic measurements are performed at baseline, and after approximately 10 years of follow-up

All cardiovascular events during follow-up

Rapid haemodynamic responses are assessed during the same measurement session (the response to head-up tilt and to research drugs salbutamol, nitroglycerin and L-arginine)

The change in haemodynamic variables after daily consumption of liquorice (2 weeks); bisoprolol (3 weeks); small milk casein-derived polypeptides (12 weeks)

Recordings are performed during normal conditions (training peroid) and after completion of a full-length Ironman competition

Spots Global Cancer Trial Database for salbutamol 400 µg (single dose, no longer given since january 2017)