title: Irradiation induced modest changes in murine cardiac function despite progressive structural damage to the myocardium and microvasculature.
abstract: BACKGROUND
  Radiotherapy of thoracic and chest wall tumors increases the long-term risk of cardiotoxicity, but the underlying mechanisms are unclear.
  
  
  METHODS
  Single doses of 2, 8, or 16 Gy were delivered to the hearts of mice and damage was evaluated at 20, 40, and 60 weeks, relative to age matched controls. Single photon emission computed tomography (SPECT/CT) and ultrasound were used to measure cardiac geometry and function, which was related to histo-morphology and microvascular damage.
  
  
  RESULTS
  Gated SPECT/CT and ultrasound demonstrated decreases in end diastolic and systolic volumes, while the ejection fraction was increased at 20 and 40 weeks after 2, 8, and 16 Gy. Cardiac blood volume was decreased at 20 and 60 weeks after irradiation. Histological examination revealed inflammatory changes at 20 and 40 weeks after 8 and 16 Gy. Microvascular density in the left ventricle was decreased at 40 and 60 weeks after 8 and 16 Gy, with functional damage to remaining microvasculature manifest as decreased alkaline phosphatase (2, 8, and 16 Gy), increased von Willebrand Factor and albumin leakage from vessels (8 and 16 Gy), and amyloidosis (16 Gy). 16 Gy lead to sudden death between 30 and 40 weeks in 38% of mice.
  
  
  CONCLUSIONS
  Irradiation with 2 and 8 Gy induced modest changes in murine cardiac function within 20 weeks but this did not deteriorate further, despite progressive structural and microvascular damage. This indicates that heart function can compensate for significant structural damage, although higher doses, eventually lead to sudden death.
authors: Division of Experimental Therapy, The Netherlands Cancer Institute, The Netherlands.
authors: Ingar
authors: I
authors: Seemann
authors: Karen
authors: K
authors: Gabriels
authors: Nils L
authors: NL
authors: Visser
authors: Saske
authors: S
authors: Hoving
authors: Johannes A
authors: JA
authors: te Poele
authors: Jeffrey F
authors: JF
authors: Pol
authors: Marion J
authors: MJ
authors: Gijbels
authors: Ben J
authors: BJ
authors: Janssen
authors: Fijs W
authors: FW
authors: van Leeuwen
authors: Mat J
authors: MJ
authors: Daemen
authors: Sylvia
authors: S
authors: Heeneman
authors: Fiona A
authors: FA
authors: Stewart
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D006321:Heart / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000528:radiation effects*; D064847:Multimodal Imaging; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000528:radiation effects; D049268:Positron-Emission Tomography; D011878:Radiotherapy / Q000009:adverse effects; D014057:Tomography, X-Ray Computed