RESUMEN
Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis.
Asunto(s)
Perfilación de la Expresión Génica , Glicoproteínas/fisiología , Ventrículos Cardíacos/anatomía & histología , Hipertrofia Ventricular Izquierda/genética , Péptidos y Proteínas de Señalización Intercelular/fisiología , Ratas/genética , Animales , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/genética , Presión Sanguínea/genética , Mapeo Cromosómico , Regulación de la Expresión Génica , Genómica , Glicoproteínas/genética , Ventrículos Cardíacos/metabolismo , Humanos , Hipertensión/complicaciones , Hipertensión/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Ratones Noqueados , Tamaño de los Órganos/genética , Sitios de Carácter Cuantitativo , Ratas MutantesRESUMEN
AIM: To review techniques of implantable cardioverter-defibrillators (ICD) in patients after Mustard surgery for arterial transposition. METHODS AND RESULTS: Retrospective analysis of all Mustard patients receiving ICDs at our institution. Five patients (median age 24 years, range 19-35, 3 male) with systemic right ventricular dysfunction (sRV) dysfunction and New York Heart Association (NYHA) II and III, received ICDs. Implantation was performed transvenously in three patients, epicardial patches and subcutaneous arrays at surgery in two patients. Two patients required lead extraction and baffle stent angioplasty before ICD implantation. Defibrillation vectors incorporating the anterior sRV mass [i.e., sub-pulmonary left ventricle (pLV) to generator can, and between epicardial defibrillator patches], consistently achieved a minimum 10 joule(J) safety margin during defibrillation threshold (DFT) testing. Subcutaneous arrays and endocardial vectors that included a superior vena cava (SVC) electrode were less effective. One patient developed pulmonary oedema post-procedure. At a median 20 months, all patients were alive and in NYHA class II. Follow-up over 24 months documented multiple non-sustained ventricular tachycardia (VT) in the group and one patient had recurrent VT with aborted device therapy. CONCLUSION: Defibrillator implantation in Mustard patients is challenging. Sub-optimal defibrillation should be anticipated and can be overcome using vectors which integrate the RV mass and high-energy devices. A staged procedure involving pre-implant interventions or separate DFT tests, where indicated, may be better tolerated by patients.