Human Cardiac Mitochondria in Acute Endocarditis and Obesity

University Hospital, Clermont-Ferrand90 enrolled

Overview

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.

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

Study Type

OBSERVATIONAL

Enrollment

Conditions

Obesity Endocarditis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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,

Outcomes

Primary Outcomes

Mitochondrial function

Measurement of oxidative phosphorylation and reactive oxygen species release in isolated human cardiac mitochondria

Time frame: at day 1 (Moment of the surgery)

Secondary Outcomes

walk test

6-minutes walk test

Time frame: 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

Time frame: 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

Time frame: at days (-10-5), (+7+10), (+30) and (+90)

Membrane lipid composition

Fatty acid composition of plasma lipids

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: at days (0) and (+30)

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Exercise testing

Time frame: at day (+30)

Patient follow-up during the hospital stay

quantity of time (h) spent by the patient during the stay in reanimation

Time frame: 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

Time frame: measurement during the post-operative 90 days