Clinical trial NCT00807521: Steroid-induced Reduction of Surgical Stress Study
Official title: Reduction of the Cardiac Proapoptotic Stress Response by Dexamethasone in Patients Undergoing Coronary Artery Bypass Grafting Surgery
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Coronary Artery Stenosis
Coronary Artery Bypass Graft Surgery
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2008-12-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Expression of p38 in cultured cells and cardiac tissue
timeFrame: One week
Secondary outcomes:
measure: 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
timeFrame: One week
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Jan R. de Jong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam UMC, location VUmc
name: dr. Christa Boer, PhD
role: STUDY_CHAIR
affiliation: Amsterdam UMC, location VUmc
name: dr. Everaldo M. Redout, PhD
role: PRINCIPAL_INVESTIGATOR
References: