Effect of Acute Hypoxia on RIght VEntRicular Function in Healthy Adults. (RIVER-H)

Effect of Acute Hypoxia on RIght VEntRicular Function. A Single-Center, Double-Blind, Randomized Controlled Cross-Over Trial.

More and more people are engaging in sports in the mountains, including individuals with heart or lung diseases. At the same time, such diseases are becoming more common in Switzerland. At high altitude, less oxygen is available, which places stress on the body-particularly on the heart, which has to pump blood through the lungs. How the healthy heart, especially the right ventricle, responds to this stress is still not well understood. Therefore, this study investigates how the heart responds to simulated altitudes of 2,500 m and 4,000 m, both at rest and during light physical activity. The present investigation focuses on healthy individuals in order to establish a reference for future comparisons with patients suffering from cardiopulmonary diseases. The primary objective is to assess how right ventricular function changes under conditions of reduced oxygen availability. In addition, vital signs, changes in blood gases, oxygen levels in blood and tissue and shortness of breath are assessed. The "altitude" is simulated using a special gas mixture that participants inhale. Healthy participants undergo three altitude conditions (490, 2,500, and 4,000 m above sea level). The order of the altitude conditions is assigned at random. The aim is to better understand how the right ventricle and other parameters respond to low-oxygen conditions and how affected patients can be better supported in the future.

Study Overview

• Status: Recruiting
• Conditions: Hypoxia; Altitude Hypoxia; Right Heart Function; Normobaric Hypoxia
• Intervention / Treatment: Other: Normobaric Hypoxia

Detailed Description

Outdoor activities in the mountains are becoming increasingly popular. At higher altitudes, the air contains less oxygen, which puts extra strain on the body-especially on the heart. The right side of the heart plays a key role in pumping blood through the lungs and may need to work harder when oxygen levels are low. While the heart's response to long-term altitude exposure is relatively well known, much less is understood about how the healthy heart reacts to short-term (acute) exposure to low oxygen, particularly during light physical activity. This study aims to better understand how the healthy right ventricle responds to short-term simulated altitude exposure. Healthy participants will be exposed to different oxygen levels that correspond to altitudes of 490 m (near sea level), 2,500 m, and 4,000 m, both at rest and during light cycling exercise. By studying healthy individuals first, the results will provide an important reference for future studies in patients with heart or lung disease.

The main focus of the study is to measure changes in right ventricular function, assessed using a non-invasive heart ultrasound technique called speckle-tracking echocardiography. In addition, heart rate, blood pressure, oxygen saturation, and symptoms such as shortness of breath and leg fatigue will be recorded.

The study is conducted at a single center and uses a randomized, double-blind, cross-over design, meaning that each participant undergoes all altitude conditions in a random order, and neither the participants nor the investigators know which altitude is being simulated at a given time.

Participants Only healthy adults aged 18-80 years will be included. Participants must live below 800 m above sea level and must not have been exposed to higher altitudes for more than 24 hours in the three weeks before participation. Individuals with significant medical conditions, pregnancy, need for long-term oxygen therapy, or inability to follow the study procedures will be excluded.

Study procedures

Each study visit includes:

• A short resting period
• Measurement of vital signs (heart rate, blood pressure, oxygen saturation)
• Heart ultrasound at rest
• A 10-minute low-intensity cycling exercise
• Repeated heart ultrasound and symptom assessment during exercise
• Low-oxygen conditions are created using a special gas mixture that participants breathe through a mask. Each condition is separated by a sufficient wash-out period to ensure recovery.

Study size and duration Based on statistical calculations, 18 participants will be recruited to allow balanced allocation across all study conditions and to account for potential dropouts. Participation may take place over two to three days, depending on the preferred schedule of the participant. The days can be spread or be spread over several weeks, depending on individual availability.

Aim of the study The goal of this study is to improve understanding of how the healthy right side of the heart responds to short-term low-oxygen exposure at rest and during light exercise. This knowledge will help interpret future findings in patients with heart or lung disease and may contribute to safer recommendations for physical activity at altitude.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mona Lichtblau, PD Dr. med.; Phone Number: +41 442552220; Email: mona.lichtblau@usz.ch
• Study Contact Backup: Name: Carmen Wick, Cand. PhD; Phone Number: +41 43 253 44 05; Email: carmen.wick@usz.ch

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Not yet recruiting
    • Consultant Clinic of Pulmonology, University Hospital of Zurich
    • Contact: Carmen Wick, Cand. PhD; Phone Number: +41 43 253 44 05; Email: carmen.wick@usz.ch
    • Principal Investigator: Mona Lichtblau, PD Dr. med.
    • Sub-Investigator: Carmen Wick, Cand. PhD
    • Sub-Investigator: Alessandro Vella, Cand. PhD
    • Contact: Mona Lichtblau, PD Dr. med.; Phone Number: +41 44 255 22 20; Email: mona.lichtblau@usz.ch
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8091
      • Recruiting
      • Consultant Clinic of Pulmonology, University Hospital of Zurich
      • Contact: Carmen Wick, Cand. PhD; Phone Number: +41 43 253 44 05; Email: carmen.wick@usz.ch
      • Contact: Mona Lichtblau, PD Dr. med.; Phone Number: 0432538176; Email: mona.lichtblau@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Signed informed consent
• 18-80 years (age group young: 18-39.99 years / age group older: 40-80 years)
• All sex and genders -Living <800m and without altitude exposure > 2500 m and > 24h within the last three weeks

Exclusion Criteria:

• <18, >80 years old -Any diagnosed cardiopulmonary condition including past HAPE
• Other clinically significant severe concomitant disease states (e.g. renal, hepatic dysfunction, etc.)
• Inability to follow the procedures of the study due to language problems, psychological neurological disorders or orthopaedic disorders
• Participants permanently living >800m and altitude exposure > 2500 m and >24h within the last three weeks
• Pregnancy: Participants will be asked if pregnant or not, no screening for undetected pregnancy
• Lactating women -Participation in other study with active treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm ABC; The participant receives first normobaric normoxia (A), then normobaric hypoxia equal to 2500 m.a.s.l. (B) then normobaric hypoxia representing 4000 m.a.s.l. (C). Condition A represents the control.	Other: Normobaric Hypoxia; Normobaric hypoxia according to 408m (control/normobaric normoxia), 2500 m and 4000 m above sea-level at rest for 1 hour and at low intensity cycling for 10 minutes (5 min 30 W, 5 min 60 W).; Other Names: rest; low intensity cycling; normobaric normoxia
Other: Arm ACB; The participant receives first normobaric normoxia (A), then normobaric hypoxia representing 4000 m.a.s.l. (C), then normobaric hypoxia equal to 2500 m.a.s.l. (B). Condition A represents the control.	Other: Normobaric Hypoxia; Normobaric hypoxia according to 408m (control/normobaric normoxia), 2500 m and 4000 m above sea-level at rest for 1 hour and at low intensity cycling for 10 minutes (5 min 30 W, 5 min 60 W).; Other Names: rest; low intensity cycling; normobaric normoxia
Other: Arm BAC; The participant receives first normobaric hypoxia equal to 2500 m.a.s.l. (B), then normobaric normoxia (A), then normobaric hypoxia representing 4000 m.a.s.l. (C). Condition A represents the control.	Other: Normobaric Hypoxia; Normobaric hypoxia according to 408m (control/normobaric normoxia), 2500 m and 4000 m above sea-level at rest for 1 hour and at low intensity cycling for 10 minutes (5 min 30 W, 5 min 60 W).; Other Names: rest; low intensity cycling; normobaric normoxia
Other: Arm BCA; The participant receives first normobaric hypoxia equal to 2500 m.a.s.l. (B), then normobaric hypoxia representing 4000 m.a.s.l. (C), then normobaric normoxia (A). Condition A represents the control.	Other: Normobaric Hypoxia; Normobaric hypoxia according to 408m (control/normobaric normoxia), 2500 m and 4000 m above sea-level at rest for 1 hour and at low intensity cycling for 10 minutes (5 min 30 W, 5 min 60 W).; Other Names: rest; low intensity cycling; normobaric normoxia
Other: Arm CAB; The participant receives first normobaric hypoxia representing 4000 m.a.s.l. (C), then normobaric normoxia (A), then normobaric hypoxia equal to 2500 m.a.s.l. (B). Condition A represents the control.	Other: Normobaric Hypoxia; Normobaric hypoxia according to 408m (control/normobaric normoxia), 2500 m and 4000 m above sea-level at rest for 1 hour and at low intensity cycling for 10 minutes (5 min 30 W, 5 min 60 W).; Other Names: rest; low intensity cycling; normobaric normoxia
Other: Arm CBA; The participant receives first normobaric hypoxia representing 4000 m.a.s.l. (C), then normobaric hypoxia equal to 2500 m.a.s.l. (B), then normobaric normoxia (A). Condition A represents the control.	Other: Normobaric Hypoxia; Normobaric hypoxia according to 408m (control/normobaric normoxia), 2500 m and 4000 m above sea-level at rest for 1 hour and at low intensity cycling for 10 minutes (5 min 30 W, 5 min 60 W).; Other Names: rest; low intensity cycling; normobaric normoxia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right ventricular free wall strain	The primary endpoint is defined as the right ventricular free wall strain (RVFWS) from condition normobaric normoxia to condition 4000m for group 1 and from normobaric normoxia to condition 2500m for group 2 at rest. RVFWS will be measured by speckle tracking strain analysis according to the guidelines of the European Association of Cardiology. Speckle tracking echocardiography allows to assess the right ventricular volume and true global RV function without relying on geometric assumption and is a valuable clinical bedside tool for assessing myocardial strain. Tomtec software (Philipps) will be used.	It will be assessed once at baseline in rest and during each condition three times: Once after 1 hour in the specific condition at rest, then during the 5 min of 30 Watt cycling and during the 5 min of 60 Watt cycling.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tricuspid annular plane systolic excursion (TAPSE)	Differences in tricuspid annular plane systolic excursion (TAPSE) [cm] between the conditions at rest and during exercise, measured according to the guidelines of the European Association of cardiology.	It will be assessed once at baseline in rest and during each condition three times: Once after 1 hour in the specific condition at rest, then during the 5 min of 30 Watt cycling and during the 5 min of 60 Watt cycling.
Right ventricular-arterial coupling	Differences in TAPSE/sPAP and RVFWS/sPAP between the conditions at rest and during exercise, measured by echocardiography, as a validated, noninvasive measure of right ventricular-arterial coupling.	It will be assessed once at baseline in rest and during each condition three times: Once after 1 hour in the specific condition at rest, then during the 5 min of 30 Watt cycling and during the 5 min of 60 Watt cycling.
RV/PA	Differences in RV/PA ratio between the conditions at rest and during exercise, measured by echocardiography according to the guidelines of the European Association of cardiology.	It will be assessed once at baseline in rest and during each condition three times: Once after 1 hour in the specific condition at rest, then during the 5 min of 30 Watt cycling and during the 5 min of 60 Watt cycling.
Stroke volume	Differences in stroke volume based on the left ventricular outflow tract diameter and the velocity time integral over the aortic valve in the apical 5-chamber view or the apical long axis view [ml] between the conditions at rest and during exercise, measured by speckle tracking strain analysis according to the guidelines of the European Association of Cardiology.	It will be assessed once at baseline in rest and during each condition three times: Once after 1 hour in the specific condition at rest, then during the 5 min of 30 Watt cycling and during the 5 min of 60 Watt cycling.
Heart rate	Differences in heart rate [bpm] and HRV between the conditions at rest and during exercise, continuously measured throughout the intervention by electrocardiogram connected to an Alice pdx.	It will be assessed at baseline and continuously measured during each condition (1 hour resting period and during the 10 minutes cycling).
Blood pressure	Differences in blood pressure between the conditions at rest and during exercise, measured by a digital sphygmomanometer four times at rest and four times during low load cycling [mmHg] and continuously measured by a PPG-based Wrist-monitor (biobeat).	It will be measured at baseline once and during each condition six times: Four times during the resting period (every 15 min) and two times during low load cycling.
Borg Rating of Perceived Exertion Scale (CR10)	Differences in Borg Rating of Perceived Exertion Scale (CR10) between the conditions at rest and during exercise. Measured through showing a paper with the 10 categories and the participant points to the according category which describes the current breathing difficulty.	Measured at baseline and in each condition twice: Once at the end of the resting condition and again at the end of the cycling exercise.
Oxygen saturation	Differences in oxygen saturation [%] between the conditions at rest and during exercise, continuously measured throughout the intervention by an oximeter connected to an Alice pdx.	It will be assessed at baseline and continuously measured during each condition (1 hour resting period and during the 10 minutes cycling).
Lung tissue oxygenation	Differences in lung tissue oxygenation between the conditions at rest and during exercise, assessed using near infrared spectroscopy (NIRS) continuously measured throughout the intervention according to our SOP.	It will be assessed at baseline and continuously measured during each condition (1 hour resting period and during the 10 minutes cycling).
Brain oxygenation	Differences in brain oxygenation between the conditions at rest and during exercise, assessed using near infrared spectroscopy (NIRS) continuously measured throughout the intervention according to our SOP.	It will be assessed at baseline and continuously measured during the 1 hour resting period during each condition, and during the 10 minutes cycling.
Respiratory effort	Differences in respiratory effort abdominal and chest using zRIP belts between the conditions at rest and during exercise connected to an Alice pdx.	It will be assessed at baseline and continuously measured during each condition (1 hour resting period and during the 10 minutes cycling).
Multiomics profiles	Differences in multiomics profiles between the conditions at rest, assessed using mass spectrometry analysis of blood serum collected from venous blood from the V. antecubita, will be evaluated to determine the effects of acute hypoxia and group-specific responses.	A blood sample will be collected during each condition after 1 hour of rest.
Arterial blood gas analysis	Differences in arterial blood gas analysis (ABGA) between the conditions at rest, collected through puncture of the A. radialis by a trained physician.	A blood sample will be collected during each condition after 1 hour of rest.
Right ventricular size	Differences in right ventricular size between the conditions at rest and during exercise, measured according to the guidelines of the European Association of cardiology.	It will be assessed once at baseline in rest and during each condition three times: Once after 1 hour in the specific condition at rest, then during the 5 min of 30 Watt cycling and during the 5 min of 60 Watt cycling.
Fractional area change	Differences in fractional area change between the conditions at rest and during exercise, measured according to the guidelines of the European Association of cardiology.	It will be assessed once at baseline in rest and during each condition three times: Once after 1 hour in the specific condition at rest, then during the 5 min of 30 Watt cycling and during the 5 min of 60 Watt cycling.
Maximal tricuspid regurgitation velocity	Differences in maximal tricuspid regurgitation velocity between the conditions at rest and during exercise, measured according to the guidelines of the European Association of cardiology.	It will be assessed once at baseline in rest and during each condition three times: Once after 1 hour in the specific condition at rest, then during the 5 min of 30 Watt cycling and during the 5 min of 60 Watt cycling.
End-diastolic diameter	Differences in end-diastolic diameter between the conditions at rest and during exercise, measured according to the guidelines of the European Association of cardiology.	It will be assessed once at baseline in rest and during each condition once at rest.
Pulmonary acceleration time	Differences in pulmonary acceleration time between the conditions at rest and during exercise, measured according to the guidelines of the European Association of cardiology.	It will be assessed once at baseline in rest and during each condition once at rest.
Diastolic dysfunction grade	Differences in diastolic dysfunction grade between the conditions at rest and during exercise, measured according to the guidelines of the European Association of cardiology.	It will be assessed once at baseline in rest and during each condition once at rest.

Collaborators and Investigators

• Sponsor: Mona Lichtblau
• Investigators: Principal Investigator: Mona Lichtblau, University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: heart rate; right ventricular function; tissue oxygenation; breathing difficulty; blood gas; right ventricular free wall strain; RVFWS
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypoxia; Dyspnea; Altitude Sickness; RE1-silencing transcription factor
• Other Study ID Numbers: RIVER-H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Anonymized individual participant data (IPD) are planned to be shared via an appropriate data repository, such as Zenodo. Corresponding standard operating procedures (SOPs) for our department are currently under development.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No