Autonomic Nervous Activity During the Systemic Inflammatory Response in Trained and Untrained Healthy Volunteers

Summary

Critical illness, severe infection, extensive trauma or tissue damage cause an inflammatory (irritative) reaction in the body. This reaction affects the whole body and causes malaise, circulatory and cardiac changes, fever, increases the number of white blood cells in the blood stream and prompts release of signaling proteins. This reaction contributes to the development of considerable organ damage and possibly organ failure. These are serious complications in critical illness which are associated with a high mortality. This inflammatory reaction is affected by the autonomic nervous system. This is the part of the nervous system, which is beyond the control of the free will, and the part that regulates circulation, breathing and digestive functions. The autonomic nervous system works via so-called sympathetic signals, which set the body in a state of alertness to overcome immediate challenges, and parasympathetic (vagal) signals, which are especially active during restitution and rest. It is known, that the balanced activity in the autonomic nervous system affects the body's inflammatory response in critical illness. A study in mice has shown that if parasympathetic (vagal) signals are blocked mortality in critical illness is increased. Reversely, when the autonomic nervous system is medically stimulated towards parasympathetic signaling, the magnitude of the inflammatory response is decreased. Nicotine exerts this stimulatory effect.

Also, we know that individuals in good physical shape have increased parasympathetic tone compared to less trained individuals. However, studies have never addressed whether this shifted balance in the autonomic nervous system affects the inflammatory response related to critical illness.

Over the last 30 years an experimental model mimicking the inflammatory response has been used in studies. Inflammation may be simulated by injecting the drug E.Coli LPS, which induces a controlled, fully reversible, harmless reaction the duration of which is a few hours. Influenza-like symptoms occur and changes in circulatory parameters and concentrations of signaling proteins can be measured.

Using this experimental model, the investigators wish to study whether this shifted balance in the autonomic nervous system in individuals in good physical shape affects the body's reaction to critical illness. Investigators also want to determine how nicotine (using a nicotine patch) affects this reaction.

Conditions

• Systemic Inflammatory Response Syndrome

Interventions

OTHER

Endotoxin

Bolus injection of LPS 2 ng/kg IV at time = 2 hours (Study day A).

OTHER

Endotoxin + Nicotine

Transdermal application of nicotine patch applied at time = -8 hours (midnight the day before Study day B) + bolus injection of LPS 2 ng/kg at time = 2 hours (Study day 2)

Sponsors & Collaborators

• Bispebjerg Hospital

  collaborator OTHER

• Rigshospitalet, Denmark

  lead OTHER

Principal Investigators

• Susanne Janum, MD · Bispebjerg Hospital/Rigshospitalet

• Kirsten Møller, MD,PhD,DMSc · Rigshospitalet, Denmark

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-06-30

Primary Completion

2013-01-31

Completion

2015-12-31

Countries

• Denmark

Study Locations