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Effects of pulmonary artery banding in doxorubicin-induced left ventricular cardiomyopathy
Authors:Can Yerebakan  Johannes Boltze  Hatem Elmontaser  Uygar Yoruker  Heiner Latus  Markus Khalil  Stefan Ostermayer  Blanca Steinbrenner  Christian Apitz  Matthias Schneider  Marcel Suchowski  Rita Ruetten  Kristin Mueller  Gunther Kerst  Dietmar Schranz  Hakan Akintuerk
Affiliation:1. Children''s National Heart Institute, The George Washington University School of Medicine and Health Sciences, Washington, DC;2. School of Life Sciences, University of Warwick, Coventry, United Kingdom;3. Pediatric Heart Center Giessen, Justus-Liebig-University, Giessen, Germany;4. Department of Pediatric Cardiology, University of Aachen, Aachen, Germany;5. Pediatric Cardiology, University of Ulm, Ulm, Germany;6. Veterinary Medicine Clinic for Small Animals, Justus-Liebig-University, Giessen, Germany;7. Institute of Pathology, Faculty of Veterinary Medicine, University Leipzig, Leipzig, Germany;8. Fraunhofer-Institute for Cell Therapy and Immunology, Leipzig, Germany
Abstract:ObjectiveCentral pulmonary banding has been proposed as a novel alternative for the treatment of left ventricular dilated cardiomyopathy in children. We sought to investigate the effects of central pulmonary banding in an experimental model of doxorubicin-induced left ventricular dilated cardiomyopathy.MethodsFour-month-old sheep (n = 28) were treated with intermittent intracoronary injections of doxorubicin (0.75 mg/kg/dose) into the left main coronary artery. A total dose of up to 2.15 mg/kg of doxorubicin was administered until signs of left ventricular dilation with functional impairment occurred by transthoracic echocardiography evaluation. Animals that survived were treated with surgical central pulmonary banding through a left anterior thoracotomy or sham surgery. Transthoracic echocardiography and pressure-volume loop measurements were used to compare left ventricular function preoperatively and 3 months later. Macroscopic and microscopic histologic examinations followed after hearts were harvested.ResultsNine animals from the central pulmonary banding group and 8 animals from the sham group survived and were included in the final analysis. Both groups showed similar inflammation and fibrosis upon histologic examination consistent with the toxic myocardial effects of doxorubicin. There were no differences in the echocardiographic measurements before central pulmonary banding or sham operation. Baseline measurements before the central pulmonary banding/sham operation were considered as 100%. The central pulmonary banding group had better left ventricular ejection fraction (102.5% ± 21.6% vs 76.7% ± 11.7%, P = .01), with a tendency for smaller left ventricular end-diastolic (101.2% ± 7.4% vs 120.4% ± 10.8%, P = .18) and significantly smaller end-systolic (100.3% ± 12.9% vs 116.5 ± 9.6%, P = .02) diameter of the left ventricle in comparison with the sham animals at 3 months. The end-systolic volume (101.4% ± 31.6% vs 143.4% ± 28.6%, P = .02) was significantly lower in the central pulmonary banding group 3 months postoperatively. Fractional shortening in the long axis (118.5% ± 21.5% vs 85.2% ± 22.8%, P = .016) and short axis (122.5% ± 18% vs 80.9% ± 13.6%, P = .0005) revealed significantly higher values in the central pulmonary banding group. In the conductance catheter measurements, no significant differences were seen between the groups for the parameters of systolic and diastolic function.ConclusionsCentral pulmonary artery banding in the setting of experimental toxic left ventricular dilated cardiomyopathy improved left ventricular echocardiographic function and dimensions.
Keywords:Address for reprints: Can Yerebakan, MD, Department of Cardiovascular Surgery, Children's National Heart Institute, The George Washington University School of Medicine and Health Sciences, 111 Michigan Ave NW, Washington, DC 20010.  cardiomyopathy  heart failure  pulmonary artery banding  left ventricle  cPAB  central pulmonary artery banding  maximal slope of systolic pressure increment  maximal slope of diastolic pressure decrement  LVEF  left ventricular ejection fraction  PAB  pulmonary artery banding  PV  pressure-volume
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