caa a22 4500 605478902 CHVBK 20210128100407.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s10741-015-9479-6 doi (NATIONALLICENCE)springer-10.1007/s10741-015-9479-6 Right ventricular failure due to chronic pressure load: What have we learned in animal models since the NIH working group statement? [Elektronische Daten] [Marinus Borgdorff, Michael Dickinson, Rolf Berger, Beatrijs Bartelds] Right ventricular (RV) failure determines outcome in patients with pulmonary hypertension, congenital heart diseases and in left ventricular failure. In 2006, the Working Group on Cellular and Molecular Mechanisms of Right Heart Failure of the NIH advocated the development of preclinical models to study the pathophysiology and pathobiology of RV failure. In this review, we summarize the progress of research into the pathobiology of RV failure and potential therapeutic interventions. The picture emerging from this research is that RV adaptation to increased afterload is characterized by increased contractility, dilatation and hypertrophy. Clinical RV failure is associated with progressive diastolic deterioration and disturbed ventricular-arterial coupling in the presence of increased contractility. The pathobiology of the failing RV shows similarities with that of the LV and is marked by lack of adequate increase in capillary density leading to a hypoxic environment and oxidative stress and a metabolic switch from fatty acids to glucose utilization. However, RV failure also has characteristic features. So far, therapies aiming to specifically improve RV function have had limited success. The use of beta blockers and sildenafil may hold promise, but new therapies have to be developed. The use of recently developed animal models will aid in further understanding of the pathobiology of RV failure and development of new therapeutic strategies. The Author(s), 2015 Pressure overload nationallicence Congenital heart diseases nationallicence Pulmonary hypertension nationallicence Pulmonary artery banding nationallicence MRI nationallicence Pressure-volume analysis nationallicence CHD : Congenital heart diseases nationallicence Ees : End-systolic elastance nationallicence Eed : End-diastolic elastance nationallicence ERA : Endothelin receptor antagonists nationallicence FAO : Fatty acid oxidation nationallicence LV : Left ventricle nationallicence MCT : Monocrotaline nationallicence PAB : Pulmonary artery banding nationallicence PDE5 : Phosphodiesterase 5 nationallicence PDK : Pyruvate dehydrogenase kinase nationallicence PKG : Protein kinase G nationallicence PH : Pulmonary hypertension nationallicence RAAS : Renin−angiotensin aldosterone system nationallicence RV : Right ventricle nationallicence Borgdorff Marinus Department of Pediatrics, Center for Congenital Heart Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut Dickinson Michael Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut Berger Rolf Department of Pediatrics, Center for Congenital Heart Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut Bartelds Beatrijs Department of Pediatrics, Center for Congenital Heart Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut Heart Failure Reviews Springer US; http://www.springer-ny.com 20/4(2015-07-01), 475-491 1382-4147 20:4<475 2015 20 10741 https://doi.org/10.1007/s10741-015-9479-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10741-015-9479-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Borgdorff Marinus Department of Pediatrics, Center for Congenital Heart Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Dickinson Michael Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Berger Rolf Department of Pediatrics, Center for Congenital Heart Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Bartelds Beatrijs Department of Pediatrics, Center for Congenital Heart Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut NATIONALLICENCE 773 0- Heart Failure Reviews Springer US; http://www.springer-ny.com 20/4(2015-07-01), 475-491 1382-4147 20:4<475 2015 20 10741