Figure.

The Experimental design is described in panel A: Group I (N=12) received a single thoracic radiation of 20 Gy at day 0, Groups II (N=6) sham non-irradiated mice were used as controls; an echocardiogram was performed at baseline (1 day prior to irradiation), 3 days, and 1, 4 and 6 months post irradiation; isoproterenol was administrated at 3 days, 4 and 6 months to measure contractile reserve. Panel B shows increased mortality in the XRT-treated group (p=0.049 vs sham non-irradiated). Panel C shows that XRT-treated mice had no significant change in LVEF up to 4 months and a significant drop in LVEF by 20% between 4 and 6 months (p<0.05 vs sham-non-irradiated). Panel D shows representative M-mode echocardiography recordings of the LV transverse mid-ventricular sections obtained before and after isoproterenol treatment in sham non-irradiated and XRT-treated mice. A M-Mode measurement of contractile reserve expressed as the change in LVEF measured before and after isoproterenol injection (a β-adrenergic agonist) is shown in panel E. The XRT-treated mice demonstrated a reduction in LV contractile reserve at 3 days, 4 and 6 months (p<0.05 vs sham-non irradiated). Interstitial myocardial fibrosis expressed as percentage of fibrotic areas on total area per field is shown in panel F, XRT-treated mice had a 2-fold increase in interstitial collagen deposition (p=0.014). Panel G shows a trend in the increment of TUNEL⁺ nuclei (indicated with and asterisk) reflecting apoptotic DNA fragmentation (p=NS).

IP=intraperitoneal, isopt=isoproterenol, XRT= XRT-treated mice, LVEF=left ventricular ejection fraction.