title: Ultrastructural changes associated with myocardial apoptosis, in failing rat hearts induced by volume overload.
abstract: BACKGROUND
  Myocardial apoptosis has been discussed to play a pivotal role in the development and progression of congestive heart failure (CHF). However, recently there is doubt on the evidence of myocardial apoptosis in heart failure as information on ultrastructural changes by electron microscopy is still scarce. This project therefore aimed to detect direct morphological evidence of myocardial apoptosis in an experimental heart failure model.
  
  
  METHODS
  Following IRB approval, an aortocaval fistula (ACF) was induced in male Wistar rats using a 16G needle. 28±2days following ACF rats were examined by hemodynamic measurements, Western blot, immunofluorescence confocal and electron microscopic analysis.
  
  
  RESULTS
  Within 28±2days of ACF heart (3.8±0.1 vs. 6.6±0.3mg/g) and lung (3.7±0.2 vs. 6.9±0.5mg/g) weight indices significantly increased in the ACF group accompanied by a restriction in systolic (LVEF: 72±2 vs. 39±3%) and diastolic (dP/dtmin.: -10,435±942 vs. -5982±745mmHg/s) function (p<0.01). Activated caspase-3 was significantly increased in failing hearts concomitant with mitochondrial leakage of cytochrome c into the cytosol. Finally, electron microscopy of the left ventricle (LV) of ACF rats revealed pronounced ultrastructural changes in >70% of examined cardiomyocytes, such as nuclear chromatin condensation, myofibril loss and disarray, contour irregularities and amorphous dense bodies, mitochondriosis and damaged cell-cell-contacts between cardiomyocytes.
  
  
  CONCLUSIONS
  Volume overload induced heart failure is associated with activation of the mitochondrial apoptotic pathway. In addition, electron microscopy of the LV revealed direct ultrastructural evidence of extended myocardial apoptosis in ACF rats.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: sascha.treskatsch@charite.de.
authors.forename: S
authors.initials: S
authors.lastname: Treskatsch
authors.affiliation: Institute of Anatomy, Ludwig-Maximilians-Universität München, München, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Shakibaei
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Feldheiser
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Shaqura
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Dehe
authors.affiliation: Department of Cardiology, Campus Charité Mitte, Charité - Universitätsmedizin, Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: T K
authors.initials: TK
authors.lastname: Roepke
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Spies
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: S A
authors.initials: SA
authors.lastname: Mousa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006333:Heart Failure / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure*; D032383:Myocytes, Cardiac / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000502:physiology
keywords: Apoptosis; Caspase-3; Cytochrome c; Electron microscopy; Heart failure; Volume overload