Steroid-induced Reduction of Surgical Stress Study

Study Overview
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Brief Summary
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The stress response as induced by myocardial cellular damage during cardiac surgery may lead to myocardial stunning and apoptosis, and could therefore impair postoperative patient recovery. Surgical trauma typically induces the liberation of cytokines. Some of these cytokines are strongly associated with the initiation of intracellular proapoptotic pathways through activation of tyrosine kinases and integrins. The latter are known for their deteriorating effects on cardiac function and are strongly involved in cardiac remodeling. Dexamethasone is typically administered prior to cardiac surgery in order to especially reduce the release of proinflammatory cytokines. It has however never been investigated whether this additionally reduces proapoptotic signaling in the human heart, thereby eliminating risk factors for the induction of cardiac dysfunction. In the present study, the investigators therefore aim to investigate whether dexamethasone inhibits proapoptotic pathways in patients undergoing cardiac surgery. Furthermore, the investigators would like to elucidate whether this proposed effect of dexamethasone is related to the reduction of the stress response in the heart or indirectly by suppression of cytokine release. For this purpose the investigators will obtain cardiac biopsies and plasma from patients, who are randomly assigned to placebo or dexamethasone treatment and undergo on and off-pump coronary artery bypass grafting (CABG) surgery.

Official Title
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Reduction of the Cardiac Proapoptotic Stress Response by Dexamethasone in Patients Undergoing Coronary Artery Bypass Grafting Surgery

Conditions
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Coronary Artery Stenosis, Coronary Artery Bypass Graft Surgery

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing coronary artery bypass surgery (CABG) Age 18-75 years Informed consent Exclusion Criteria: Re-operations and emergency operations Patient with anemia (Hb < 5.0) Emergency operation Patients receiving blood transfusions < 3 months before operation Insulin depended diabetes mellitus Hepatic or renal failure Pregnancy Use of steroids

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>High dose bolus of dexamethasone before surgery | Drug: Dexamethasone<br>* Single high dose bolus of dexamethasone before surgery<br>|
| Placebo Comparator: 2<br>Placebo control | Drug: Placebo<br>* Placebo for dexamethasone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of p38 in cultured cells and cardiac tissue |  | One week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pro-apoptotic signaling, precursor peptides of ANP (proANP), vasopressin (Copeptin), proET-1 and Adrenomedullin (proADM). Age, gender, length, body weight, hematocrit, Hb, leukocytes, surgery time, clamp time, CPB time |  | One week |