title: A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation.
abstract: OBJECTIVE
  Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC) and heterotopic heart transplantation (hHTx) in rats.
  
  
  METHODS
  To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations.
  
  
  RESULTS
  50 TAC procedures were performed with a survival of 92% (46/50). When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm²) (p = 0.001) after three weeks with a fractional shortening (FS) of 23.7± 4.3% vs. 28.2± 1.5% (p = 0.01). Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p = 0.0001) and left ventricular inner surface increased to 19.9±1.1 mm² (p = 0.0001). Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46). All transplanted organs survived two weeks of mechanical unloading.
  
  
  CONCLUSIONS
  Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure.
authors: Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany.|DZHK (German Center for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors: Andreas
authors: A
authors: Schaefer
authors: Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany.|DZHK (German Center for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors: Yvonne
authors: Y
authors: Schneeberger
authors: DZHK (German Center for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.|Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Justus
authors: J
authors: Stenzig
authors: Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany.
authors: Daniel
authors: D
authors: Biermann
authors: Department of Cellular and Integrative Physiology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Marisa
authors: M
authors: Jelinek
authors: Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany.|DZHK (German Center for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors: Hermann
authors: H
authors: Reichenspurner
authors: DZHK (German Center for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.|Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Thomas
authors: T
authors: Eschenhagen
authors: DZHK (German Center for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.|Department of Cellular and Integrative Physiology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Heimo
authors: H
authors: Ehmke
authors: DZHK (German Center for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.|Department of Cellular and Integrative Physiology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Alexander P
authors: AP
authors: Schwoerer
mesh_terms: D000818:Animals; D001011:Aorta / Q000601:surgery; D006332:Cardiomegaly / Q000503:physiopathology* / Q000601:surgery; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology* / Q000601:surgery; D016027:Heart Transplantation / Q000379:methods*; D006353:Heart-Assist Devices; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D016042:Transplantation, Heterotopic / Q000379:methods*; D020257:Ventricular Remodeling