Mechanisms of Exercise Intolerance in Chronic Obstructive Pulmonary Disease (COPD)

1: Is endothelium function impaired in COPD? Other chronic cardiovascular diseases are associated with endothelial dysfunction, and the endothelium plays an important role in regulating vascular tone, tissue blood flow, coagulation and the inflammation process. Although the specific causes of endothelial dysfunction remain unclear, physical inactivity, chronic systemic inflammation and smoking are all known to be associated with endothelial abnormality.

2. Is Muscular Sympathetic Nerve Activity (MSNA) increased in COPD? A balanced regulation of blood flow to skeletal muscles may be disturbed by pathophysiology and may therefore contribute to the exercise intolerance and skeletal muscle depletion seen in patients with COPD.Skeletal muscle blood flow is tightly regulated to match tissue oxygen demands and is thus adapted to meet energy requirements. During physical activity, the sympathetic nervous system is activated ("exercise pressor reflex"), resulting in increased ventilation, heart rate and a redistribution of cardiac output from inactive to active tissues. The redistribution of cardiac output to the body organs is heterogeneous. Blood flow to skeletal, respiratory and cardiac muscle increases as exercise intensity increases, whereas blood flow to gastrointestinal, renal and reproductive tissues decreases. As blood pressure during exercise remains largely unchanged, the redistribution of blood flow is caused by changes in vascular conductance. These conductance changes are caused by an overall vasoconstriction induced by the increased sympathetic outflow of noradrenaline (NA), and a vasodilation of vascular beds supplying the working skeletal -, cardiac- and respiratory muscle.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Other: Exercise

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

Contacts and Locations

Study Locations

• Denmark
  • Capital Region
    • Copenhagen, Capital Region, Denmark, 2100
      • Centre of Physical Activity Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Forced Expiratory Volume at on second/ Forced Vital Capacity fixed ratio <0.70, - Forced Expiratory Volume at one second <60% of predicted and Medical
• Research Council scale > or equal to 3
• Arterial oxygen saturation at rest> 90%,
• Body Mass Index >18,
• Left Ventricle Ejection Fraction> 45.

Exclusion Criteria:

• Unstable ischemic heart disease,
• severe heart valve failure,
• pulmonary emboli,
• severe heart failure,
• severe infections,
• musculoskeletal disorders,
• malignant disease,
• contraindicated medicine as anticoagulants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COPD; Acute exercise bouts	Other: Exercise
Active Comparator: Healthy; Acute exercise bouts	Other: Exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelium function during acute exercise (one legged kicking) by Flow doppler	Flow doppler	On one experimental day during acute exercise (one legged knicking) and change from baseline
Muscular Sympathetic Nerve Activity During acute exercise (handgrip and leg isometric leg extension) by Peroneal microneurography		On one experimental day during acute exercise (handgrib and leg isometric leg extension) and change from baseline

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: January 19, 2015
• First Submitted That Met QC Criteria: February 5, 2015
• First Posted (Estimate): February 11, 2015

Study Record Updates

• Last Update Posted (Estimate): June 16, 2016
• Last Update Submitted That Met QC Criteria: June 15, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: H-2-2013-150 - project 2