Cardiopulmonary Bypass, Coronary Artery Bypass Surgery
Conditions
Keywords
Coronary artery bypass graft surgery (CABG), Cardiopulmonary Bypass (CPB), Cyclosporine, ischaemia reperfusion
Brief summary
Observe the effect of preliminary cyclosporine administration on different markers of cardiac ischaemia led by the aortic cross-clamp during coronary artery bypass surgery with Cardiopulmonary bypass.
Detailed description
The coronary artery bypass surgery, in spite of substantial improvements during the last years, is still associated to a post-operative mortality and morbidity: myocardial infarction, heart failure, cardiac arrhythmia, renal failure, Stroke. These complications are often due to ischaemia - reperfusion injury event. Recent studies showed that in case of cellular stress (in particular during the reperfusion after ischaemia) a not specific pore, called Mitochondrial permeability transition Pore (MPTP), could be opened. That caused the loss of ion homeostasis, then cell death as well as by apoptosis as by necrosis. Prevent the opening of this MPTP during the myocardial reperfusion after coronary bypass, for example, is an important objective to improve the cardioprotection. The Cyclosporin A, prevents the MPTP from opening. Several studies have shown an cytoprotection led by cyclosporin A, after ischaemia reperfusion in several models as isolated rats heart, in vivo rats heart and ex vivo myocardial ( atrial ) human tissues. Recently, a multicentric study performed in humans, during the acute phase of myocardial infarction, showed a reduction of infarct size by approximately 40% in the cyclosporine group compared to control group.
Interventions
DRUGSandimmum
Intravenous injection of cyclosporine
DRUGPlacebo
Intravenous Injection of NaCl solution
Sponsors
University Hospital, Grenoble
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient hospitalized for a coronary artery bypass surgery * Not urgent surgery * Left ventricular ejection fraction (LVEF)\> 40 % * 18 years and older * patient who have sign the informed consent form * Affiliation to the French Social Security.
Exclusion criteria
* Beating heart surgery with or without Cardiopulmonary Bypass * Patient receiving another surgical gesture combined to the CABG * Myocardial infarction or vascular cerebral attack less than 30 days * Previous History of cardiac surgery; * Renal failure (creatinine \> 200 µmol/l) * Uncontrolled hypertension * hyperkaliemy; * hyperuricemy; * Acute Coronary Syndrome * Malignant tumor * Unchecked infection * Previous intravenous administration of Sandimmun ®; * allergy to ciclosporin, ethyl alcohol, castor oil or nitrogen * Pregnant Woman, parturient without contraception, or breast-feeding * Age \< 18 years * Patient who have not signed the form of consent; * Patient Under guardianship or being the object of a legal protective measure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass | at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass. |
Secondary
| Measure | Time frame |
|---|---|
| Area under curve and maximal blood level of S100β protein | at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass |
| Spontaneous defibrillation at aorta declamping; Post surgical atrial fibrillation; ECG (new Q wave); Transthoracic Echocardiogram (diastolic and systolic function study, research of paradoxical septal motion, study of cardiac output)....) | until Day 3 after the end of the cardiopulmonary bypass |
| Levels of inflammatory cytokines (TNF alpha , IL-1 alpha et IL-1 beta, IL-6, IL-8, IL-10). C-reactive protein (CRP) level | until day 8 after the end of the cardiopulmonary bypass |
| Creatine blood levels | until 3 months after the end of the cardiopulmonary bypass |
Countries
France
Outcome results
None listed