Mixoma auricular izquierdo gigante que causa obstrucción valvular mitral, hipertensión pulmonar y tromboembolia pulmonar / Giant atrial myxoma causing mitral valve obstruction, pulmonary hypertension and pulmonary thromboembolism

Resumen: Los tumores cardíacos pueden ser primarios o, más frecuentemente secundarios o metastásicos. Entre los tumores primarios es más frecuente el mixoma, cuya ubicación más común es en la aurícula izquierda. Las manifestaciones clínicas son diversas, producidas principalmente por obstrucción mecánica, embolizaciones, y manifestaciones constitucionales. Se comunica el caso de un paciente de 32 años, con cuadro clínico de insuficiencia cardíaca, hipertensión pulmonar severa y tromboembolismo pulmonar bilateral. Se hizo el diagnóstico de mixoma auricular izquierdo. Se resecó el tumor y se manejó la hipertensión pulmonar desde el ingreso al hospital con inhibidores de la fosfodiesterasa asociado a anticoagulación. Se discute el tema dando énfasis a aspectos fisiopatológicos involucrados tanto en la hipertensión pulmonar como en la presencia de tromboembolia pulmonar.

Abstract: Cardiac tumors may be primary or, more frequently secondary or associated to metastasis. Atril myxoma es the most frequent primary tumor, usually located in the left atrium. Clinical manifestations include those due to mitral valve occlusión, emboli and general non spedific symptoms and signs. Herein we report the clinical case of a 32 year old patient with severe pulmonary hypertension and bilateral pulmonary embolism. The tumor was extirpated, and he received phosphoro-diesterase inhiborts and anticoagulants. Subsequent clinical course was satisfactory. A brief discussion of this condicion is included.

What can molecular modelling bring to the design of artificial inorganic cofactors?

In recent years, the development of synthetic metalloenzymes based on the insertion of inorganic catalysts into biological macromolecules has become a vivid field of investigation. The success of the design of these composites is highly dependent on an atomic understanding of the recognition process between inorganic and biological entities. Despite facing several challenging complexities, molecular modelling techniques could be particularly useful in providing such knowledge. This study aims to discuss how the prediction of the structural and energetic properties of the host-cofactor interactions can be performed by computational means. To do so, we designed a protocol that combines several methodologies like protein-ligand dockings and QM/MM techniques. The overall approach considers fundamental bioinorganic questions like the participation of the amino acids of the receptor to the first coordination sphere of the metal, the impact of the receptor/cofactor flexibility on the structure of the complex, the cost of inserting the inorganic catalyst in place of the natural ligand/substrate into the host and how experimental knowledge can improve or invalidate a theoretical model. As a real case system, we studied an artificial metalloenzyme obtained by the insertion of a Fe(Schiff base) moiety into the heme oxygenase of Corynebacterium diphtheriae. The experimental structure of this species shows a distorted cofactor leading to an unusual octahedral configuration of the iron with two proximal residues chelating the metal and no external ligand. This geometry is far from the conformation adopted by similar cofactors in other hosts and shows that a fine tuning exists between the coordination environment of the metal, the deformability of its organic ligand and the conformational adaptability of the receptor. In a field where very little structural information is yet available, this work should help in building an initial molecular modelling framework for the discovery, design and optimization of inorganic cofactors. Moreover, the approach used in this study also lays the groundwork for the development of computational methods adequate for studying several metal mediated biological processes like the generation of realistic three dimensional models of metalloproteins bound to their natural cofactor or the folding of metal containing peptides.