Aortic Cross-Clamping and Systemic Inflammatory Response in Humans: Effect of Ischemic Preconditioning

Study Overview
=================
Brief Summary
-----------------
Multiple organ dysfunction syndrome is a major cause of morbidity and mortality after abdominal aortic aneurysm (AAA) surgery. It is postulated that aortic cross-clamping during open AAA repair may cause ischemia-reperfusion (I/R) leading to the systemic releases of reactive oxygen species (ROS) and inflammatory cytokines which damage distant organs, including heart, kidney, and lung. Ischemic preconditioning, first described in cardiac surgery, is a mechanism whereby tissues exposed to a brief period of nonlethal I/R develop resistance to subsequent ischemic insult. Remote ischemic preconditioning (RIPC), is a phenomenon whereby brief periods of ischemia followed by reperfusion in one organ (usually skeletal muscle) provide systemic protection from prolonged ischemia. The mechanisms through which RIPC confer organ protection remains unclear. The hypothesis is that limb RIPC would reduce systemic inflammatory mediators produced by ischemia-reperfusion and thereby protect the remote organs. A single-center, prospective, randomized, parallel-group controlled trial is conducted on patients undergoing elective open infrarenal AAA repair. Written informed consent is obtained from each participant. The study protocol was reviewed and approved by the Research Ethics Committee of Rouen, France. Patients are divided in two groups : the sham-operated control group underwent surgery without RIPC and the RIPC group : Two cycles of intermittent crossclamping of the common iliac artery (right or left) with 10 minutes ischemia followed by 10 minutes reperfusion served as the RIPC stimulus, before prolonged ischemia. Blood samples are collected for analysis at the following time points: before surgery (baseline), 1, 3 and 24 h after cross-clamp release (reperfusion). The systemic inflammatory response is measured using the serum concentrations of TNF-alpha, and IL 1, 4, 6, 10. Cardiac, renal and pulmonary functions are evaluated with usual biological markers and clinical monitoring until 28 days after surgery. Aortic surgery is a perfect clinical model of ischemia-reperfusion which makes it possible to study the impact of RIPC in humans. This biological approach would help to better understand the mechanisms underlying this technique.

Official Title
-----------------
Aortic Cross-Clamping and Systemic Inflammatory Response in Humans: Effect of Ischemic Preconditioning

Conditions
-----------------
Aortic Aneurysm

Intervention / Treatment
-----------------
* Procedure: Remote ischemic preconditioning
* Biological: Blood drawn


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients undergoing elective open infrarenal abdominal aortic aneurysm repair Scheduled surgery Patients aged 30-85 years old Exclusion Criteria: Patients undergoing endovascular treatment for infrarenal abdominal aortic aneurysm Patients younger than 30 years and older than 85 years pregnant women or nursing mother Adult under guardianship Refusal to sign a consent Patients whose survival at 28 days is unlikely Surgery requiring subphrenic aortic cross-clamping Emergency surgery Patients taking sulfonylureas or Nicorandil Patients having contraindication to clamp iliac arteries Dementia

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients undergoing aortic aneurysm surgery with RIPC<br>Blood drawn is done for patient undergoing elective open infrarenal abdominal aortic aneurysm repair surgery with Remote ischemic preconditioning (RIPC) | Procedure: Remote ischemic preconditioning<br>* Remote ischemic preconditioning is done for patients undergoing elective open infrarenal abdominal aortic aneurysm repair<br>Biological: Blood drawn<br>* Blood drawn is done for patients undergoing elective open infrarenal abdominal aortic aneurysm repair<br>|
| Sham Comparator: Patients undergoing aortic aneurysm surgery without RIPC<br>Blood drawn is done for patient undergoing elective open infrarenal abdominal aortic aneurysm repair surgery without Remote ischemic preconditioning (RIPC) | Biological: Blood drawn<br>* Blood drawn is done for patients undergoing elective open infrarenal abdominal aortic aneurysm repair<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood TNF-alpha rate | Blood TNF-alpha rate is measured after reperfusion | 24 hours post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood lactates rate | Blood lactates rate is measured after reperfusion | 24 hours post-surgery | 
| Blood I-CAM protein rate | Blood I-CAM protein rate is measured after reperfusion | 24 hours post-surgery | 
| Blood Interleukines 1 rate | Blood Interleukines 1 rate is measured after reperfusion | 24 hours post-surgery | 
| Blood Interleukines 4 rate |  | 24 hours post-surgery | 
| Blood Interleukines 6 rate | Blood Interleukines 1 rate is measured after reperfusion | 24 hours post-surgery | 
| Blood Interleukines 10 rate | Blood Interleukines 10 rate is measured after reperfusion | 24 hours post-surgery |