the Influence of Remote Ischemic Preconditioning on Inflammation During Human Endotoxemia

Summary

In a wide range of auto-inflammatory and infectious diseases attenuation of the immune response could be beneficial. Remote ischemic preconditioning (RIPC) has been identified as a means of protecting patients undergoing cardiac surgery from perioperative myocardial ischemic damage. This protection can be divided in a 'first window of protection' directly after preconditioning and a 'second window' that protects patients 12-48 hour after preconditioning. Repeated RIPC might have additional value, possibly by combining beneficial effects of the first and second windows of protection. The mechanisms behind these effects are under investigation, but attenuation of the inflammatory response is a major candidate. However, this has not yet been demonstrated in the setting of systemic inflammation in humans in vivo. This study aims to investigate the effects of (repeated) ischemic preconditioning on inflammation during human endotoxemia.

Conditions

• Autoimmune Diseases
• Infection

Interventions

OTHER

Multiple-dose Remote Ischemic Preconditioning

A blood-pressure cuff with handheld rubber inflation balloon and manometer is placed on the non-dominant arm of the subject. The cuff will be placed proximally from the elbow with the most proximal part of the cuff placed in the armpit. The cuff will be inflated to 250 mmHg after which a 5 minute countdown is started. After 5 minutes the pressure is released and the 5 minute countdown for reperfusion is started. This concludes one cycle out of a total of four. 1 "RIPC-dose" consists of 4 cycles of 5 minute ischemia followed by 5 minute reperfusion as described above. Multiple-dose RIPC consists of a daily dose of 1 RIPC as described above for 7 consecutive days.

OTHER

Single-dose Remote Ischemic Preconditioning

A blood-pressure cuff with handheld rubber inflation balloon and manometer is placed on the non-dominant arm of the subject. The cuff will be placed proximally from the elbow with the most proximal part of the cuff placed in the armpit. The cuff will be inflated to 250 mmHg after which a 5 minute countdown is started. After 5 minutes the pressure is released and the 5 minute countdown for reperfusion is started. This concludes one cycle out of a total of four. 1 "RIPC-dose" consists of 4 cycles of 5 minute ischemia followed by 5 minute reperfusion as described above. Single-dose RIPC consists of 1 dose of RIPC as described above

BIOLOGICAL

LPS infusion

To achieve a controlled inflammatory state, 30 subjects (multiple-dose RIPC group \[n=10\], single-dose RIPC group \[n=10\] and control group \[n=10\]) will receive LPS intravenously. The LPS at a dose of 2 ng/kg iv will be injected in 1 minute.

Sponsors & Collaborators

• Radboud University Medical Center

  lead OTHER

Principal Investigators

• Jelle Zwaag, MSc · Radboud University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-10-31

Primary Completion

2016-03-31

Completion

2016-03-31

Countries

• Netherlands

Study Locations