Human Cardiac Mitochondria in Acute Endocarditis and Obesity

Study Overview
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Brief Summary
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Data about human cardiac mitochondria are cruelly lacking in the literature. However, damages of the activity of these organelles are often the source of abnormal cardiac function in several pathologies. The purpose of this study is to develop a model of purified human cardiac mitochondria, to verify the purity of these organelles and to validate the authenticity of their function in acute endocarditis and obesity, two situations known to alter their activity. Animal studies have shown that microbial infection reduced mitochondrial metabolism whereas obesity increases it. The investigator's hypotheses are the following: 1) acute endocarditis, a form of cardiac microbial infection, reduces the function of human cardiac mitochondria; 2) obesity (body mass index > 30) activates the metabolism of human cardiac mitochondria.

Detailed Description
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3 groups of patients: Controls: patients with normal weight (23 < BMI < 27) operated for myocardial revascularization by bypass surgery, without infarction, or for valve pathologies without endocarditis Endocarditis: patients with normal weight (23 < BMI < 27) carriers of endocarditis with surgery indication Obese: obese patients (BMI > 30) operated for myocardial revascularization by bypass surgery, without infarction, or for valve pathologies without endocarditis Comparisons studied: Controls vs. endocarditis Controls vs. obese patients

Official Title
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Development of the Purification of Human Cardiac Mitochondria, Characterization of These Organelles and Validation of the Model in Acute Endocarditis and Obesity

Conditions
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Obesity, Endocarditis

Intervention / Treatment
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* Other: Endocarditis
* Other: Obese vs. control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For the controls : adult patients with normal body weight (23 < BMI < 27) necessitating a cardiac surgery with sternotomy and extracorporeal circulation for myocardial revascularization or valve replacement For endocarditis : adult patients with normal body weight (23 < BMI < 27) and endocarditis of bacterial origin necessitating a cardiac surgery with sternotomy and extracorporeal circulation in order to cure a major valve regurgitation or vegetation with higher size than 15 mm with embolic risk For obese patients: adult patients with high body weight (BMI > 30 and waist to hip ration > or = 1 for men and 0.85 for women) necessitating a cardiac surgery with sternotomy and extracorporeal circulation for myocardial revascularization or valve replacement For all the patients: Ability to furnish an enlightened agreement Menbership of the French social security insurance Exclusion Criteria: Criteria linked to the surgery: Surgery of pressing emergency Aortic dissection Redux surgery Criteria linked to the patient: Protocol refusal Protected adult patients Previous psychiatric pathology including known addiction states Physical or intellectual inability Preexisting pathologies such as respiratory failure Cardiac failure (ejection fraction < 30% pulmonary hypertenstion > 80 mmHg); aortic counterpulsation; pre-operatory cardiogenic shock Severe acute or chronic renal failure with creatinine clearance < 40 ml/min Inherited dyslipidemia Previous cardiac or thoracic surgery with pericardium opening Severe hepatic failure and severe chronic hepatic pathologies Evolving neoplasia Patients with long course corticoid treatment and with inflammatory diseases Patients with double anti-platelet treatment not stopped 48h before the surgery Protected people not involved in the study: pregnant women, nursing women, guardianship, deprived of liberty,

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 |
| --- | --- |
| Control<br>patients with normal weight (23 < BMI < 27) operated for myocardial revascularization by bypass surgery, without infarction, or for valve pathologies without endocarditis | Other: Endocarditis<br>* Comparison : Endocarditis vs. control<br>|
| Endocarditis<br>patients with normal weight (23 < BMI < 27) carriers of endocarditis with surgery indication | Other: Endocarditis<br>* Comparison : Endocarditis vs. control<br>|
| Obese<br>obese patients (BMI > 30 with waist to hip ratio > or = 1 in men and 0.85 in women) operated for myocardial revascularization by bypass surgery, without infarction, or for valve pathologies without endocarditis | Other: Obese vs. control<br>* Comparisons : Obese vs. control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mitochondrial function | Measurement of oxidative phosphorylation and reactive oxygen species release in isolated human cardiac mitochondria | at day 1 (Moment of the surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| walk test | 6-minutes walk test | at the moment of inclusion in the study (day (-10-5)) and of the end of hospitalization (day +7+10) | 
| body composition | determination of lean masses by impedance-metry | 1 day before the surgery | 
| Electrocardiogram : Detections of the rates in events per min of arrhythmias | Detections of the rates in events per min of arrhythmias (existence of P wave followed by a QRS complex) and atrio-ventricular blocks in all the patients | at days (-10-5), (+7+10), (+30) and (+90) | 
| Membrane lipid composition | Fatty acid composition of plasma lipids | at day 1 (at the day of surgery) | 
| Markers of oxidative stress in the plasma | Markers of the oxidative stress in the plasma (amounts of thiol groups and TBARS, activities of SOD, catalase, glutathione peroxidase, ratio between the amounts of GSH and GSSG) and in the myocardium (whole myocardium: ratio between the activities of aconitase and fumarase, amount of protein carbonylation; isolated mitochondria: amount of nitrosylated proteins) | at days (0) and (+30) for the plasma and day (0) for the myocardium | 
| Concentrations of inflammation cytokines in the plasma | Inflammatory cytokines in the plasma (IL-6, IL-1b, TNF-a, fibrinogen, CRP and pro-calcitonin | at days (-10-5), (0), (+1), (+2), (+7) and (+90) | 
| Semi-quantitative analysis of the amounts of approximatively 6000 molecules in the plasma by metabolomic and lipidomic techniques | Studies performed in the plasma by a U.S. private society (Metabolon) | at days (0) and (+30) | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Exercise testing | at day (+30) | 
| Patient follow-up during the hospital stay | quantity of time (h) spent by the patient during the stay in reanimation | morbi-mortality at day (+90) | 
| Morbi-mortality | rates of deaths and complications (cardiac, renal, hepatic, etc.) during the 90 days following the surgery for all the patients | measurement during the post-operative 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart, Mitochondria, Obesity, Endocarditis