Abstract 15830: ‘Out of Target’ Radiation Therapy Leads to Impaired Cardiac Contractile Reserve in the Mouse

Introduction: Radiation therapy (XRT) used for the treatment of cancer, can expose the heart to the radiation beam causing cardiac injury. However, fatigue and exercise intolerance are common symptoms in patients treated with XRT for different types of cancer, in which the XRT field does not involve the heart. Hypothesis: We hypothesize that impaired cardiac reserve may occur even when the XRT field is distant from the heart (‘out of target effect’). Methods: C57BL/6J female mice underwent two different radiation treatments (20 Gray, single dose) using a Small Animal Radiation Research Platform: a) the isocenter was pointed to the right lung sparing the heart (‘out of target’) and b) the heart was chosen as isocenter, as positive control. An additional group of mice were sham-irradiated, as negative control. Transthoracic echocardiography was used to assess the left ventricular ejection fraction (LVEF) at baseline and the contractile reserve expressed as percentage change in the LVEF measured at rest (LVEFr) and 3 minutes after intraperitoneal administration of the β-adrenergic agonist, isoproterenol (LVEFi)[(LVEFi-LVEFr)/LVEFr]*100]. Results: Three days after radiation treatment irradiated and sham mice showed normal LVEF at rest. However, the ‘out of target’ irradiation group showed a significant impairment in cardiac contractile reserve compared with sham, and similar to the ‘on target’ group (Figure). Conclusions: ‘Out of target’ radiation therapy leads to impaired cardiac contractile reserve in the mouse.