Cardiovascular Morbidity
Conditions
Keywords
air pollution, ozone, fine particle, cytokine, chemokine, oxidative stress, inflammation, heart rate variability, autonomic nervous system, sympathetic nerve activity, plasma catecholamine
Brief summary
The primary hypothesis of the study is that in healthy elderly subjects experimental exposure to air pollutants increases sympathetic nervous system activity compared with sham (clean air) exposure. The secondary hypothesis of the study is that combined experimental exposure to air pollutants (particles + ozone) increases sympathetic nervous system activity to a greater extent than does the exposure to particles alone.
Detailed description
In a randomized, double-blind, and cross-over fashion, the participants will be exposed to clean air, ultrafine particles, or ultrafine particles and ozone in an exposure chamber. The investigators will determine blood pressure, heart rate, respiration as well as cardiac output and directly record sympathetic vasomotor tone using the microneurography technique. To elucidate the underlying mechanisms through which particles and ozone affect the autonomic nervous system, the investigators will assess the local and systemic inflammatory response as well as the changes in neurotrophic factors in sputum and blood. In addition, the activation of inflammatory cells in sputum and blood will be analyzed at different points in time after exposures. Changes in sympathetic activity will be correlated with the degree of airway inflammation and oxidative stress assessed in induced sputum and blood. This study will provide important insight in the mechanisms through which air pollution, particularly ultrafine particle exposure, increases cardiovascular risk in human subjects and generate a human model for mechanistic and therapeutic studies.
Interventions
OTHERultrafine particles
exposure to ultrafine particles
OTHERultrafine particles and ozone
exposure to ultrafine particles and ozone
OTHERclean air
Exposure to clean air.
Sponsors
Fraunhofer-Institute of Toxicology and Experimental Medicine
Hannover Medical School
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Elderly man or postmenopausal woman older than 50 years of age. * Signed written informed consent.
Exclusion criteria
* Smoker. * Cardiovascular and/or pulmonary disease. * Medication with relevant impact on autonomic system function, e. g. norepinephrine reuptake inhibitors. Stable medication with slight to moderate autonomic effects is tolerable. * Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol. * Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. * Subject unlikely to comply with protocol, e. g. uncooperative attitude or unlikelihood of completing the study. * Known hypersensitivity to ozone. * History of drug or alcohol abuse. Particles Study - Protocol version: October 19, 2012 14 * Blood donation of more than 500 mL during the previous 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Muscle sympathetic nerve activity (MSNA) | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of sympathetic vasoconstrictor nerve activity directed to skeletal muscle expressed as sympathetic bursts per minute. The primary hypothesis of the study is that in healthy elderly subjects experimental exposure to air pollutants increases sympathetic nervous system activity compared with sham (clean air) exposure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MSNA burst incidence | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of MSNA expressed as bursts/100 heart beats. |
| total MSNA | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of MSNA expressed as burst area/min. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Total peripheral resistance | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change in total peripheral resistance expressed as dyn\*s/cm\^5. |
| Heart rate variability. | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change in heart rate variability parameters in the time and frequency domain. |
| Plasma norepinephrine concentration | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of plasma norepinephrine in ng/l. |
| Plasma renin concentration | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of plasma renin concentration in |
| Baroreflex sensitivity | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change in baroreflex sensitivity expressed as ms/mmHg. |
| Blood pressure | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of blood pressure in mmHg. |
| Oxidative stress parameters | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of plasma malondialdehyde(MDA)concentration. |
| Correlation between inflammation, oxidative stress and cardiovascular regulation | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Correlation coefficients between changes in parameters for inflammation and oxidative stress with changes in cardiovascular parameters. |
| Forced expiratory volume in one second (FEV1) | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change in FEV1 in l |
| Forced vital capacity (FVC) | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change in FVC in l. |
| Percentage of neutrophils in peripheral blood | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of percentage of neutrophils in peripheral blood. |
| Inflammation parameters | 3.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of the percentage of neutrophils in induced sputum. |
| Heart rate | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of heart rate in beat per minute. |
| Cardiac output | 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone | Change of cardiac output in l/min. |
Countries
Germany
Contacts
Primary ContactMarcus May, MD
Outcome results
None listed