title: Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction.
abstract: BACKGROUND
  Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are unknown. We used an experimental approach based upon clinical signs of RVF to delineate functional and biological processes associated with RVF.
  
  
  RESULTS
  Wistar rats were subjected to a pulmonary artery banding (PAB n=12) or sham surgery (CON, n=7). After 52±5days, 5/12 PAB rats developed clinical symptoms of RVF (inactivity, ruffled fur, dyspnea, ascites) necessitating termination (PAB+CF). We compared these to PAB rats with RVF without clinical symptoms (PAB-). PAB resulted in reduced cardiac output, RV stroke volume, TAPSE, and increased end diastolic pressure (all p<0.05 vs. CON) in all rats, but PAB+CF rats were significantly more affected than PAB-, despite similar pressure load (p=ns). Pressure-volume analysis showed enhanced contractility (end systolic elastance) in PAB- and PAB+CF, but diastolic function (end diastolic elastance, end diastolic pressure) deteriorated especially in PAB+CF. In PAB+CF capillary density was lower than in PAB-. Gene-array analysis revealed downregulation of both fatty acid oxidation and carbohydrate metabolism in PAB+CF.
  
  
  CONCLUSIONS
  Chronic PAB led to different degrees of RVF, with half of the rats developing severe clinical symptoms of RVF, associated with progressive deterioration of diastolic function, hypoxia-prone myocardium, increased response to oxidative stress and suppressed myocardial metabolism. This model represents clinical RVF and allows for unraveling of mechanisms involved in the progression from RV adaptation to RV failure and the effect of intervention on these mechanisms.
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, The Netherlands; Cardiovascular Center-laboratory for Experimental Cardiology, Graduate School of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: m.a.j.borgdorff@umcg.nl.
authors.forename: Marinus A J
authors.initials: MA
authors.lastname: Borgdorff
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, The Netherlands; Cardiovascular Center-laboratory for Experimental Cardiology, Graduate School of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Anne Marie C
authors.initials: AM
authors.lastname: Koop
authors.affiliation: University of Groningen, University Medical Center Groningen, Laboratory of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, Beatrix Children's Hospital, Groningen, The Netherlands.
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bloks
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, The Netherlands; Cardiovascular Center-laboratory for Experimental Cardiology, Graduate School of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dickinson
authors.affiliation: Leiden University Medical Center, Department of Cardiology, Leiden, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.affiliation: Cardiovascular Center-laboratory for Experimental Cardiology, Graduate School of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Herman H W
authors.initials: HH
authors.lastname: Sillje
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, The Netherlands; Cardiovascular Center-laboratory for Experimental Cardiology, Graduate School of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Maarten P H
authors.initials: MP
authors.lastname: van Wiechen
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, The Netherlands; Cardiovascular Center-laboratory for Experimental Cardiology, Graduate School of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Rolf M F
authors.initials: RM
authors.lastname: Berger
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, The Netherlands; Cardiovascular Center-laboratory for Experimental Cardiology, Graduate School of Medical Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Beatrijs
authors.initials: B
authors.lastname: Bartelds
mesh_terms: D000818:Animals; D002196:Capillaries / Q000254:growth & development / Q000473:pathology; D006328:Cardiac Catheterization; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D002908:Chronic Disease; D003971:Diastole; D005355:Fibrosis; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D010805:Physical Conditioning, Animal; D011651:Pulmonary Artery / Q000473:pathology; D017208:Rats, Wistar; D013599:Systole; D014463:Ultrasonography; D018497:Ventricular Dysfunction, Right / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D017725:Ventricular Pressure
keywords: Hypertrophy; Microarray; Pressure–volume loops; Pulmonary artery banding; Right ventricular dysfunction