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difficulties to include patients
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| cyclosporin | Active Comparator | Intravenous cyclosporin injection. |
|
| Pacebo | Placebo Comparator | Intravenous injection of NaCl solution. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sandimmum | Drug | Intravenous injection of cyclosporine |
| |
| Placebo |
| Measure | Description | 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. |
| Measure | Description | 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)....) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vincent BACH, MD | Cardiac Surgery Department - University Hospital of Grenoble, | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of cardiac surgery - University Hospital of Grenoble | Grenoble | 38043 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10393078 | Background | Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999 Jul 15;341 ( Pt 2)(Pt 2):233-49. | |
| 14962470 | Background | Halestrap AP, Clarke SJ, Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection. Cardiovasc Res. 2004 Feb 15;61(3):372-85. doi: 10.1016/S0008-6363(03)00533-9. |
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| Drug |
Intravenous Injection of NaCl solution |
|
| 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 |
| 14659807 | Background | Hausenloy DJ, Duchen MR, Yellon DM. Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia-reperfusion injury. Cardiovasc Res. 2003 Dec 1;60(3):617-25. doi: 10.1016/j.cardiores.2003.09.025. |
| 15961375 | Background | Shanmuganathan S, Hausenloy DJ, Duchen MR, Yellon DM. Mitochondrial permeability transition pore as a target for cardioprotection in the human heart. Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H237-42. doi: 10.1152/ajpheart.01192.2004. |
| 18669426 | Background | Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, Andre-Fouet X, Revel D, Kirkorian G, Monassier JP, Derumeaux G, Ovize M. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med. 2008 Jul 31;359(5):473-81. doi: 10.1056/NEJMoa071142. |