To examine the impact of age and physical fitness on the ability of ischaemic preconditioning to protect endothelial damage in response to ischaemia reperfusion injury in healthy humans. A secondary objective is to explore the role of Toll-like…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in endothelial function (measured with flow mediated dilation) after
ischaemia reperfusion injury (induced by 20 minutes ischemia) with and without
precedence of ischaemic preconditioning (by 3 cycles of 5-minutes of
ischaemia).
Secondary outcome
Activation of PBMCs by plasma as measured in an ex-vivo assay.
Background summary
Ischaemic preconditioning (IP) refers to the reduction of ischemia-reperfusion
injury induced by a brief preceding period of ischemia. Also the arterial
endothelium can be protected by IP. Several studies performed in animals and
humans have demonstrated that the protective effects of IP are attenuated with
aging. However, no previous study directly examined the underlying mechanisms
of this observation. Possibly, the reduced protective effect of IP with aging
relates to a direct effect on the endothelium, consequently leading to an
attenuated ability of IP to prevent endothelial dysfunction after ischaemia
reperfusion injury.
Several previous studies failed to demonstrate the ability of pharmacological
stimuli to mimic the beneficial effects of IP in aged vessels. Restoration of
the age-related reduction in effectiveness of IP may be possible through
exercise training. In aged animals, physical training restores the efficacy of
ischemic preconditioning. Indirect evidence indicates that physical activity,
independent of other cardiovascular risk factors, protects against a occurrence
as well as the severity of a myocardial infarction in humans. Although this
suggests that physical activity may beneficially influence the age-related
reduction in IP, no previous study provided direct evidence for this
hypothesis.
Study objective
To examine the impact of age and physical fitness on the ability of ischaemic
preconditioning to protect endothelial damage in response to ischaemia
reperfusion injury in healthy humans. A secondary objective is to explore the
role of Toll-like receptor (TLR) signalling in the induction of IP in young and
old subjects.
Study design
cross-sectional observation
Study burden and risks
Non-invasive cuff occlusion is used to examine endothelial function (5-minute
ischaemia), apply ischaemic preconditioning (3 cycles of 5-minute ischaemia)
and produce the stimulus that induces ischaemia-reperfusion injury (20-minute
ischaemia). This repeated cuff inflation is non-invasive and not associated
with a health risk for the subject. Blood will be drawn three times for ex-vivo
analysis of TLR signalling. The volunteers will not benefit directly from
participating in this study.
Geert Grooteplein-noord 21
6525 EZ Nijmegen
NL
Geert Grooteplein-noord 21
6525 EZ Nijmegen
NL
Listed location countries
Age
Inclusion criteria
-Healthy young volunteers : age 18-30
-Healthy sedentary older volunteers: age >55 years + sedentary (<1 h exercise per week)
-Healthy trained older volunteers: age >55 years + trained (>5 h exercise per week)
-All subjects: written informed consent
Exclusion criteria
-Smoking
-History of any cardiovascular disease
-Hypertension (in supine position: systole >140 mmHg, diastole >90 mmHg)
-Diabetes Mellitus (fasting glucose >7.0 mmol/L or random glucose >11.0 mmol/L)
-Hyperlipidaemia (fasting total cholesterol >6.5 mmol/L)
-Chronic use of medication known to interfere with the cardiovascular system
-Professional athletes
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL35881.091.11 |