Peter Agger1,2, Satyan Lakshminrusimha3, Christoffer Laustsen2,4, Sylvia Gugino5, Jesper R Frandsen6, Morten Smerup1, Robert H Anderson7, Vibeke Hjortdal1,2, Robin H Steinhorn8. 1. Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark. 2. Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark. 3. Division of Neonatology, Women and Children's Hospital of Buffalo, State University of New York at Buffalo, Buffalo, New York. 4. MR Research Centre, Aarhus University Hospital, Aarhus, Denmark. 5. Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York. 6. Center for Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark. 7. Institute of Genetic Medicine, University of Newcastle, Newcastle-upon-Tyne, UK. 8. Division of Neonatology, UC Davis Children's Hospital, Sacramento, California.
Abstract
BACKGROUND: Persistent pulmonary hypertension in the newborn remains a syndrome with high mortality. Knowledge of changes in myocardial architecture in the setting of heart failure in persistent pulmonary hypertension is lacking, and could aid in the explanation of the prevailing high mortality. METHODS: Persistent pulmonary hypertension was induced by antenatal ligation of the arterial duct in six ovine fetuses. The hearts were compared ex vivo with five matched control hearts, using diffusion tensor imaging to provide the overall anatomical arrangement, and assessment of the angulations and course of the cardiomyocytes. Fibrosis was assessed with histology. RESULTS: We found an overall increase in heart size in pulmonary hypertension, with myocardial thickening confined to the interventricular septum. An increase of 3.5° in angulation of myocyte aggregations was found in hypertensive hearts. In addition, we observed a 2.2% increase in collagen content in the right ventricular free wall. Finally, we found a previously undescribed subepicardial layer of strictly longitudinally oriented cardiomyocytes confined to the right ventricle in all hearts. CONCLUSION: Myocardial fibrosis and possibly changes in angulations of myocytes seem to play a part in the etiology of persistent pulmonary hypertension. Moreover, a new anatomical arrangement of right ventricular mural architecture is described.
BACKGROUND: Persistent pulmonary hypertension in the newborn remains a syndrome with high mortality. Knowledge of changes in myocardial architecture in the setting of heart failure in persistent pulmonary hypertension is lacking, and could aid in the explanation of the prevailing high mortality. METHODS: Persistent pulmonary hypertension was induced by antenatal ligation of the arterial duct in six ovine fetuses. The hearts were compared ex vivo with five matched control hearts, using diffusion tensor imaging to provide the overall anatomical arrangement, and assessment of the angulations and course of the cardiomyocytes. Fibrosis was assessed with histology. RESULTS: We found an overall increase in heart size in pulmonary hypertension, with myocardial thickening confined to the interventricular septum. An increase of 3.5° in angulation of myocyte aggregations was found in hypertensive hearts. In addition, we observed a 2.2% increase in collagen content in the right ventricular free wall. Finally, we found a previously undescribed subepicardial layer of strictly longitudinally oriented cardiomyocytes confined to the right ventricle in all hearts. CONCLUSION:Myocardial fibrosis and possibly changes in angulations of myocytes seem to play a part in the etiology of persistent pulmonary hypertension. Moreover, a new anatomical arrangement of right ventricular mural architecture is described.
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