Mechanisms of functional tricuspid valve regurgitation in ischemic cardiomyopathy

In heart failure, the presence of functional mitral regurgitation secondary to a myocardial infarction (MI) is known to double mortality. While the mechanism of functional mitral regurgitation has been extensively studied, the mechanism of a concomitant functional tricuspid regurgitation has been neglected. We hypothesized that MI alters not only the geometry of the left ventricle but also of the right ventricle leading to both ischemic mitral and tricuspid regurgitation (IMR & ITR). We also hypothesized that these geometric alterations modulate mechanical stresses resulting in molecular changes. To answer these hypotheses, the following Aims were designed: (1) complete an anatomy study of the normal tricuspid valve following the established principles applied to the mitral valve; (2) perform an in vivo sonometric study of the functional anatomy of the atrioventricular valves in order to clarify their relationships; (3) compare in sheep the data obtained with transthoracic echocardiography (TTE) with those acquired with sonomicrometry. Evaluation of the reliability of the echo geometric data is essential given its value because of its non-invasiveness. (4) develop a reproducible animal model of IMR and ITR and analyze the resulting geometrical changes (5) search for variations in eNOS and nNOS expression at increasing distance from the MI as an indicator of cardiomyocyte stretch.; Results. (1) An original terminology of the tricuspid valve useful to surgeons and cardiologists was developed; (2) we showed how the mitral and tricuspid valves are linked by the septum; (3) TTE in sheep provides precise information needed for the non invasive follow up of the LV remodeling; (4) an original animal model of IMR and ITR was developed with the percutaneous selective injection of ethanol. Specific geometrical distortions of both ventricles that resulted in IMR and ITR were found; (5) we showed that the expression of cNOS was correlated with the distance from the MI and thus the amount of stress.; Conclusion. This data suggest that IMR and ITR are caused by a geometrical distortion of both atrioventricular valves and that this macroscopic remodeling was associated with an up-regulation of eNOS that may be correlated with an adapatative process of the stretched cardiomyocytes.