Effects of Dynamic Hyperinflation on the Left-ventricular Diastolic Function in Healthy Male Subjects

Study Overview
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Brief Summary
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The aim of this study is to identify whether actively induced dynamic hyperinflation can cause left-ventricular diastolic dysfunction in healthy male subjects in order to explore the mechanisms of developing cardiac dysfunctions in patients with COPD.

Detailed Description
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Cardiovascular diseases, especially left-ventricular diastolic dysfunction, are among the most frequent reasons for morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Dynamic hyperinflation is one of the expected pathophysiological mechanisms in the multifactorial genesis of this left-ventricular diastolic dysfunction in patients with COPD. The novel concept of Expiratory Stenosis Breathing (ESB) is based on the method of Metronome-Paced Tachypnea (MPT) of Cooper et al. Therefore the investigators use a metronome to indicate a specific breathing frequency (BF) and the relation of inspiration : expiration (I : E) in order to let subjects hyperinflate. Subjects get split into two groups each hyperinflating three times for 90sec by one of the two methods before doing a cross-over and switch groups to do the same in the other group. At the end of the 90sec there is a measurement of the Inspiratory Capacity (IC) and an echocardiography in order to objectify dynamic hyperinflation respectively the change in diastolic function. During ESB participants hyperinflate with a BF - 30/min and a I : E - 1 : 3. In addition they have to breathe through an expiratory-effective stenosis (3, 2 and 1,5mm) on the mouthpiece of the pneumotachograph to simulate the collapsing airways in COPD-patients. In contrast, during MPT subjects hyperinflate with a BF - 40/min, I : E - 1 : 1; BF - 40/min, I : E - 1 : 2; BF - 30/min, I : E - 1 : 2. During the whole trial investigators measure Intrinsic Positive Endexpiratory Pressure (PEEPi) in order to objectify the dynamic hyperinflation more significantly. The primary goal of this study is to assess if actively induced dynamic hyperinflation can affect diastolic function of the left ventricle. Furthermore a correlation between the extent of dynamic hyperinflation and diastolic dysfunction should be quantified. In addition measurement of PEEPi should validate the method of Metronome-paced Tachypnea (MPT) because the investigators hypothesize that this method does not simulate the pathophysiological circumstances in patients with COPD sufficiently.

Official Title
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Effects of Dynamic Hyperinflation on the Left-ventricular Diastolic Function in Healthy Male Subjects

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Procedure: Metronome-paced tachypnea
* Procedure: Expiratory-stenosis breathing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI <27 kg/m2 Lifelong nonsmoker (currently non-smoking and up to now less than 100 cigarettes) Exclusion Criteria: Obstructive pulmonary diseases (asthma, COPD) Cardiovascular diseases (cardiac insufficiency, coronary heart diseases, hypertonia) Other relevant pulmonary or cardiac diseases Baseline E/A-ratio <1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metronome-paced tachypnea<br>Dynamic hyperinflation by the method of metronome-paced tachypnea. | Procedure: Metronome-paced tachypnea<br>* three cycles: breathing frequency (BF) - 40/min, inspiration : expiration (I : E) - 1 : 1; BF - 40/min, I : E - 1 : 2; BF - 30/min, I : E - 1 : 2<br>* Other names: MPT;|
| Experimental: Exspiratory-stenosis breathing<br>Dynamic hyperinflation by the method of expiratory-stenosis breathing. | Procedure: Expiratory-stenosis breathing<br>* three cycles: BF - /min, I : E - 1 : 3; stenosis: 3mm; 2mm; 1,5mm<br>* Other names: ESB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| E/A-ratio (absolute change between tidal breathing and smallest stenosis) | E/A-ratio will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function. | At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| E/E'-ratio | E/E'-ratio will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function. | At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds). | 
| deceleration time of the E-wave transmitral (msec) | deceleration time will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function. | At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds). | 
| Maximal diastolic transtricuspid flow (m/sec) | Maximal diastolic transtricuspid flow will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function. | At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds). | 
| Maximal late-systolic velocity of the lateral tricuspid valve in Tissue Doppler Imaging (cm/sec) | Maximal late-systolic velocity will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function. | At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds). | 
| Inspiratory Capacity | Inspiratory Capacity will be measured with a pneumotachograph (VenThor D-22/5B, ThorMedical, Budapest, Hungary). It represents the extent of dynamic hyperinflation. | At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds). | 
| Dynamic Intrinsic Positive Endexpiratory Pressure: | To objectify the dynamic hyperinflation in addition to the Inspiratory Capacity, the Intrinsic Positive Endexpiratory Pressure will be measured by the invasive application of an esophageal balloon catheter (ICU-Lab, Kleistek Engineering, Bari, Italy). | During each entire cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dynamic hyperinflation, diastolic dysfunction, COPD, Chronic Obstructive Pulmonary Disease, Metronome-paced Tachypnea, Expiratory-stenosis Breathing