Our team has shown in a series of past publications that contractile properties are heterogeneous in the heart. There is a gradient of cellular contractility across the left ventricle allowing the heart to compensate for differential wall stress during ventricular filling (Figure 1). This gradient of contractility is progressively lost during heart failure due to preferential contractile defects of the myocytes from the sub-endocardial layer (inner layer within the ventricle).
Defects at the cellular level translate to defects at the whole heart level that can be studied by non-invasive techniques such as echocardiography. Those properties have been described in different species of rodents (rat, ferret, and guinea-pig) and in bigger mammals such as dog, in healthy and different heart failure models such as ischemic, pressure overload and genetic animal models of the human Duchenne Muscular Dystrophy (DMD) such as the Golden Retriever Muscular Dystrophy (GRMD) dogs.
Figure 1 : Direct relationship between the pump function of the heart and the properties of the cardiac contractile system
Our research is focused on correlating in vivo and in vitro contractile properties in various conditions of cardiac stress in health and disease (genetic, environmental, chronic diseases). Because there is a direct relationship between the pump function of the heart and the properties of the cardiac contractile system (Figure 1 part A), a particular interest is in the mechanisms that underlie dysfunction of the contractile apparatus in cardiac diseases.
Our research employs both experimental animal models of disease as well as human investigations in collaboration with medical services of Montpellier University hospital. We focus on calcium homeostasis and regulation of contractile protein.
Our methods use technics that range from in vivo echocardiography to intact electrically stimulated cardiac myocyte (Figure 1B) and attached single cells to study specifically the contractile machinery (Figure 1part C).
- Service de cardiopédiatrie, CHRU Montpellier, France.
- Service de Médecine nuclaire, CHRU Montpellier, France.
- Service d’onco-hématologie pédiatrique, CHRU Montpellier, France.
- Service de Biochimie, CHRU Montpellier, France.
Major Publications :
- Andre L, Fauconnier J, Reboul C, Feillet-Coudray C, Meschin P, Farah C, Fouret G, Richard S, Lacampagne A, Cazorla O.(2013) Subendocardial increase in reactive oxygen species production affects regional contractile function in ischemic heart failure. Antioxid Redox Signal. 20;18(9):1009-20
- André L, Gouzi F, Thireau J, Meyer G, Boissiere J, Delage M, Abdellaoui A, Feillet-Coudray C, Fouret G, Cristol JP, Lacampagne A, Obert P, Reboul C, Fauconnier J, Hayot M, Richard S, Cazorla O. (2011) Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress.. Basic Res Cardiol. 106(6):1235-46.
- Ait mou Y, Toth A, Cassan C, Czuriga D, Detombe PP, Papp Z, Lacampagne A, Cazorla O. (2011) Beneficial effects of SR33805 in failing myocardium.. Cardiovascular Research 91(3):412-9.
- Cazorla O & Lacampagne A. (2011) Regional variation in myofilament length-dependent activation.. Pflugers Arch. 462(1):15-281.
- Cazorla O, Lucas A, Poirier F, Lacampagne A, Lezoualc’h F. (2009) The cAMP binding protein Epac regulates cardiac myofilament function.. Proc Natl Acad Sci U S A. 18;106(33):14144-9
- Ait mou Y, Reboul C, Andre L, Lacampagne A, Cazorla O. (2009) Late exercise training improves non-uniformity of transmural myocardial function in rats with ischaemic heart failure. Cardiovascular Research 81(3):555-64.