The Impact of Age and Fitness on Reperfusion Injury and Ischemic Preconditioning to Prevent This Injury

NCT01606410 | Completed

• 1 other identifier: IRI-IPC-aging
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: 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. 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.

Conditions

Cardiovascular Disease

Outcome Measures

Primary Outcomes (1)

• endothelial reperfusion injury

  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).

  cross-sectional observation (single time point)

Study Arms (4)

young, sedentary

Other: IPC

young, active

Other: IPC

old, sedentary

Other: IPC

old, active

Other: IPC

Interventions

IPC OTHER

repeated cuff inflation (220 mmhg) around an upper limb for 5 minutes, followed by 5 minutes of reperfusion (repeated 4 times)

old, active; old, sedentary; young, active; young, sedentary

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population: Young sedentary volunteers (n=23, age 18-30), young active volunteers (n=23, age 18-30), older sedentary subjects (n=23, \>55 years) and older physically active subjects (n=23, \>55 years).

You may qualify if:

• Healthy young volunteers : age 18-30
• Healthy older volunteers: age \>55 years
• Sedentary: \<1 h exercise per week
• Trained: \>5 h exercise per week
• All subjects: written informed consent

You may not qualify if:

• 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
• BMI \>30 kg/m2

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Department of Physiology

Nijmegen, 6525 EX, Netherlands

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Study Officials

• Dick Thijssen, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2012
• First Posted: May 25, 2012
• Study Start: April 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: November 20, 2013

Record last verified: 2013-11

Locations

NL (1)