The Importance of Wnt-signaling After Cardiac Surgery

Study Overview
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Brief Summary
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Cardiac surgery saves lives when patients suffer from cardiac disease. Local inflammation is important for tissue repair and wound healing after such an operation. Inflammation starts already when the patient is treated in the intensive care unit. When inflammatory proteins (cytokines) are released into the circulation, they cause also a systemic inflammation, which alerts the immune system of the body and activates defence mechanisms (=adaptive response). In some patients, systemic inflammation is out of control thereby causing organ dysfunctions, shock, and in the most severe cases even death (=maladaptive response). The aim of this study is to investigate the early phase of inflammation after the operation. Repeated blood samples will be taken of patients undergoing cardiac surgery to describe the patterns and dynamics of inflammation proteins. A better understanding of these mechanisms will potentially lead to improved treatment of patients after cardiac surgery.

Detailed Description
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The aim of this project is to understand early inflammation mechanisms after cardiac surgery. Therefore, repeated blood samples of patients undergoing cardiac surgery will be taken. Patients are selected after open cardiac surgery (via sternotomy), when when they require postoperative care in the cardiovascular intensive care unit. The blood samples will be analysed in collaboration with the Inflammation Research Unit of the Department of Internal Medicine at the University Hospital Zurich.

Official Title
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The Importance of Wnt-signaling in the Pathobiology of Systemic Inflammation and Organ Dysfunction After Cardiac Surgery

Conditions
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Inflammation, Thoracic Surgery

Intervention / Treatment
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* Other: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cardiac surgery via sternotomy Coronary-bypass bypass surgery with or without valve surgery Postoperative hospitalisation in the cardio-surgical ICU Available informed consent Exclusion Criteria: Preoperative infections (e.g. endocarditis) Preoperative use of steroids or other immunosuppression

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Coronary artery bypass surgery off-pump (n=24) | Other: Blood sampling<br>* Five Timepoints: baseline (pre-operative), ICU admission, 4 hours after ICU admission, 8 hours after ICU admission, 48 hours after ICU admission<br>|
| 2<br>Coronary artery bypass surgery on-pump (n=16) | Other: Blood sampling<br>* Five Timepoints: baseline (pre-operative), ICU admission, 4 hours after ICU admission, 8 hours after ICU admission, 48 hours after ICU admission<br>|
| 3<br>Coronary artery bypass surgery plus valve surgery (n=20) | Other: Blood sampling<br>* Five Timepoints: baseline (pre-operative), ICU admission, 4 hours after ICU admission, 8 hours after ICU admission, 48 hours after ICU admission<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of Wnt5a (ng/ml) | Measured by a commercially available ELISA | Up to 48 hours after ICU admission | 
| Plasma concentration of sFRP1 (ng/ml) | Measured by a commercially available ELISA | Up to 48 hours after ICU admission | 
| Plasma concentration of sFRP5 (ng/ml) | Measured by a commercially available ELISA | Up to 48 hours after ICU admission | 
| Plasma concentration of WIF-1 (pg/ml) | Measured by a commercially available ELISA | Up to 48 hours after ICU admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily fluid balance (ml) | Routine parameter taken from charts | Up to 48 hours after ICU admission | 
| Occurrence of complications (yes/no): composite endpoint of hemodynamic instability (defined as norepinephrine concentration = or > 0.1mcg/kg/min), delirium (defined as ICDSC score = or > 4), infections | Routine parameter taken from charts | Up to 7 days after ICU admission | 
| Length of ICU stay (days) | Routine parameter taken from charts | Up to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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WNT, Inflammation, Cardia surgery, Cardio-pulmonary bypass, Cytokines