Volume load-induced right ventricular failure in rats is not associated with myocardial fibrosis

Background Right ventricular (RV) function and failure are key determinants of morbidity and mortality in various cardiovascular diseases. Myocardial fibrosis is regarded as a contributing factor to heart failure, but its importance in RV failure has been challenged. This study aims to assess whether myocardial fibrosis drives the transition from compensated to decompensated volume load-induced RV dysfunction.MethodsWistar rats were subjected to aorto-caval shunt (ACS, n = 23) or sham (control, n = 15) surgery, and sacrificed after 1 month, 3 months, or 6 months. Echocardiography, RV pressure-volume analysis, assessment of gene expression and cardiac histology were performed.ResultsAt 6 months, 6/8 ACS-rats (75%) showed clinical signs of RV failure (pleural effusion, ascites and/or liver edema), whereas at 1 month and 3 months, no signs of RV failure had developed yet. Cardiac output has increased two- to threefold and biventricular dilatation occurred, while LV ejection fraction gradually decreased. At 1 month and 3 months, RV end-systolic elastance (Ees) remained unaltered, but at 6 months, RV Ees had decreased substantially. In the RV, no oxidative stress, inflammation, pro-fibrotic signaling (TGF beta 1 and pSMAD2/3), or fibrosis were present at any time point.ConclusionsIn the ACS rat model, long-term volume load was initially well tolerated at 1 month and 3 months, but induced overt clinical signs of end-stage RV failure at 6 months. However, no myocardial fibrosis or increased pro-fibrotic signaling had developed. These findings indicate that myocardial fibrosis is not involved in the transition from compensated to decompensated RV dysfunction in this model.Therapeutic cell differentiatio

Preventie en behandeling van scoliose bij kinderen met ernstige cerebrale parese, een inventariserend onderzoek

Background: Scoliosis, a lateral curvature of the spine, is a common problem in children with severe cerebral palsy (CP) and has far-reaching consequences including those for trunk balance, activities of daily living (ADL) and quality of life. Unclarity exists about risk factors for scoliosis in children with severe CP and about treatment of this condition. National guidelines on diagnostics and treatment of scoliosis in children with severe CP are lacking. Therefore the aim of this study was to explore by means of a questionnaire current professional practice in diagnosis and treatment of scoliosis in children with severe CP. Methods: A questionnaire, which contained 45 questions, has been sent to pediatric rehabilitation physicians, pediatric orthopedic surgeons, pediatric physiotherapists and occupational therapists from November 2009 to January 2010. The questions focussed on prevalence, physical examination, radiography and treatment with physiotherapy, occupational therapy, spinal bracing, seat inclinations, lying support systems and surgery of scoliosis in children with severe CP. In the data-analysis, mainly descriptive statistics have been used. Findings: The respons rate of physicians was approximately 25 percent; that of therapists was considerably lower. The data of the questionnaires demonstrated considerable agreement between the different professions, regarding physical examination and radiography of scoliosis in children with severe CP. The same was true for the different forms of treatment. All professions focussed for treatment on the presence and progression of scoliosis in children with severe CP. However, the results also suggested that pediatric orthopedic surgeons focussed more on ADL. Treatment options considered most important were physiotherapy, occupational therapty and the application of seat inclinations. Remarkably, no standard rules for diagnosis, including those about positioning the child regarding radiography, were used. Conclusion: One the one hand, the study showed that various groups of professionals in general have similar ideas about diagnostics and treatment of scoliosis in children with severe CP. On the other hand, standards regarding diagnosis are absent. The development of guidelines for diagnostic and treatment options for scoliosis in patiënts with severe CP is urgently needed as the presence of standard diagnostics and standard therapeutic programs allows for a valid evaluation of factors playing a role in the progression or prevention of scoliosis.