Irradiation induced cardiac damageIrradiation induced modest changes in murine cardiac function despite progressive structural damage to the myocardium and microvasculature
Section snippets
Mice and irradiation procedure
Male C57BL/6J mice aged 8–12 weeks (from Charles River Laboratories, France) were randomly allocated to different treatment groups and housed in a temperature-controlled room with 12 h light–dark cycle. Standard mouse chow and water were provided ad libitum. During irradiation or sham treatment (0 Gy) unanaesthetized mice were held in a prone position, in restraining jigs with the thorax fixed using adjustable hinges. Single doses of 2, 8, or 16 Gy were given to the heart using 250 kV X-rays,
Mouse survival and weight
There were very few unscheduled deaths after 2 and 8 Gy cardiac irradiation, although heart/body weight ratios of irradiated mice were 12–13% lower than in age-matched controls at 40 weeks and body weights were reduced by 6–13% at 60 weeks (Table 1). After 16 Gy, 38% of mice died or had to be humanely killed between 30 and 40 weeks. Because of these unscheduled deaths, all remaining animals in the 16 Gy group were killed at 40 weeks.
Non-invasive cardiac imaging
SPECT/CT and ultrasound were used to examine whether irradiation
Discussion
This study demonstrated that irradiation affects cardiac structure and microvascular function in a dose and time-dependent manner, with substantial damage after intermediate and high dose irradiation (8 and 16 Gy) and minor alterations after lower doses (2 Gy). Moreover, high doses induced changes at earlier time points and these effects progressed in time.
The transient increase in MVD at 20 weeks after 2 and 8 Gy was presumably due to stimulated proliferation in response to damage, whereas
Conflict of interest statement
There were no conflicts of interest.
Acknowledgments
The authors thank Bert Pool, Department of Nuclear Medicine, The Netherlands Cancer Institute, for help with the NanoSPECT/CT and Dr. Jack Cleutjens, Department of Pathology, the University of Maastricht, for help with the Leica Qwin morphometry system.
This research was funded by the European Atomic Energy Community’s Seventh Framework Program, grant 211403 (Cardiorisk), and the Dutch Cancer Foundation, grant NKI 2008-3993.
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Cited by (0)
- 1
These authors contributed equally (performing experiments and analyses).
- 2
These authors contributed equally (designing and supervision of the study).