Impact de la Carence Martiale et de Son Traitement Sur le métabolisme Mitochondrial du Cardiomyocyte (MitoCardioFer)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 2
- 主要终点
- Measure of the maximal activity of the mitochondrial complex I using spectrometry
研究概览
简要总结
Iron is involved in essential functions of the body. It allows the transport of oxygen in the blood, via hemoglobin, at the muscular level, via myoglobin, and it is also involved in cellular metabolism in general, in particular for the production of ATP at the mitochondrial level, within the cytochromes and iron-sulfur proteins of the respiratory chain.
Recently, iron deficiency has been identified as an important prognostic factor in heart failure patients. Iron therapy improves symptoms and physical performances of heart failure patients, even in the absence of anemia. As a result, the correction of iron deficiency is now proposed as one of the therapies for heart failure. However, the pathophysiology of the association between cardiac dysfunction and iron deficiency is still poorly understood.
The investigators previously developed a mouse model of iron deficiency without anemia, in which the investigators observed impaired physical performances, a decrease of left ventricular ejection fraction, and a decrease in mitochondrial complex I activity. These abnormalities were normalized after iron injection. These animal data suggest that iron deficiency is responsible for left ventricular dysfunction secondary to mitochondrial I complex abnormalities, and that iron therapy corrects them.
Iron deficiency is very common in the preoperative period of cardiac surgery, affecting 40 to 50% of patients. During this surgery, it is possible to perform a myocardial biopsy without risk to the patient.
The purpose of this study is to verify in patients requiring valvular heart surgery, if iron deficiency is responsible for a decrease in mitochondrial complex I activity and a decrease in cardiac function during the perioperative period, and to verify whether iron treatment improves these abnormalities.
详细描述
Iron is involved in essential functions of the body. It allows the transport of oxygen in the blood, via hemoglobin, at the muscular level, via myoglobin, and it is also involved in cellular metabolism in general, in particular for the production of ATP at the mitochondrial level, within the cytochromes and iron-sulfur proteins of the respiratory chain.
Iron deficiency has been shown to be responsible for fatigue and muscle weakness, regardless of the presence of an anemia. Recently, iron deficiency has been identified as an important prognostic factor in heart failure patients, with a prevalence increasing with NYHA class level, and association with mortality. Iron therapy improves the symptoms of heart failure patients and the 6-minute walk test, even in the absence of anemia. The correction of iron deficiency is now proposed as one of the therapies for heart failure. However, the pathophysiology of the association between cardiac dysfunction and iron deficiency is still poorly understood.
The investigators previously developed a mouse model of iron deficiency without anemia, in which the investigators observed impaired physical performances, a decrease of left ventricular ejection fraction, and a decrease in mitochondrial complex I activity. These abnormalities were normalized after iron injection. These animal data suggest that iron deficiency is responsible for left ventricular dysfunction secondary to mitochondrial I complex abnormalities, and that iron therapy corrects them.
Iron deficiency is very common in the preoperative period of cardiac surgery, affecting 40 to 50% of patients. During this surgery, it is possible to perform a myocardial biopsy without risk to the patient. There is therefore an opportunity to further explore the impact of iron deficiency and its treatment on mitochondrial energy metabolism of cardiomyocytes. We hypothesize that the activity of the mitochondrial complex I is decreased in the presence of iron deficiency and that the iron treatment corrects this decrease.
The purpose of this study is to verify in patients requiring valvular heart surgery, if iron deficiency is responsible for a decrease in mitochondrial complex I activity and a decrease in cardiac function during the perioperative period, and to verify whether iron treatment improves these abnormalities.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Patients that must be operated for a valvular heart surgery (aortic or mitral) scheduled in the month which follows the anaesthesia consultation (visit of inclusion)
- •The preoperative iron status is known
- •Patient signed informed consent
排除标准
- •Refusal of the patient to participate
- •Refusal of the surgeon or the anaesthetist who are responsible of patient management
- •Patients with a known iron overload (for example : hemochromatosis)
- •Counter-indication in the realization of a sternal bone marrow biopsy or myocardial biopsy (for example : endocarditis)
- •Adult patients under legal guardianship
- •Pregnancy
结局指标
主要结局
Measure of the maximal activity of the mitochondrial complex I using spectrometry
时间窗: At the time of the myocardial biopsy
Measure of the maximal complex I activity using spectrometry on isolated mitochondria from myocardial biopsy.
次要结局
- Quantification of the number of mitochondria per cardiomyocyte using Western-Blot(At the time of the myocardial biopsy)
- Quantification and analysis of the complex I assemblage using BN-PAGE(At the time of the myocardial biopsy)
- Quantification of myoglobin in cardiomyocytes using Western-Blot(At the time of the myocardial biopsy)
- Measure of the maximal activity of the others mitochondrial complexes using spectrometry (Complexes II, III and IV)(At the time of the myocardial biopsy)
- Cardiac function using echocardiography in pre-, intra- and post-operative periods(At the time of the myocardial biopsy)