Abstract 14774: Preserved Left Ventricular Contractile Reserve After Thoracic Irradiation in the Interleukin-1 Receptor Knock Out Mouse
Background: Thoracic irradiation (XRT), in the treatment of many cancers, is associated with the development of cardiomyopathy. In mice, XRT induces interleukin-1 (IL-1) in the heart and lungs and cause impairment in contractile reserve early after XRT, despite a normal resting cardiac function. We propose to assess the role of IL-1 on the long-term effects of XRT-induced cardiomyopathy.
Methods: We exposed C57BL/6J wild type (wt) or IL-1 receptor type I knock out mice (IL-1RI KO, not responsive to IL-1)(N=12/group) to 2 doses of XRT (14 or 20 Gray [Gy]). Echocardiography was performed to assess left ventricular (LV) ejection fraction (EF) at baseline, and 4 months after XRT. Isoproterenol (a beta-adrenergic receptor agonist, 10 ng/mouse) was used to measure the contractile reserve (change in LVEF [%]). LV catheterization was use to measure the LV end diastolic pressure (LVEDP), LV peak systolic pressure (LVPSP), +dP/dT and [[Unable to Display Character: –]]dT/dP. Sham-XRT mice were used as controls.
Results: Wt mice showed a mild significant reduction in resting LVEF at 20 Gy compare to sham-XRT (58.5±1.8% vs 65.6±2.2% sham, p<0.05, Figure) while KO showed no changes with either doses of XRT. The contractile reserve was significantly reduced in wt in a dose-dependent manner (+7.0±2.1% 20 Gy; +12.9±2.9% 14 Gy, vs sham +30.8±3.9%, P<0.002) but was preserved in the KO (+23.1±5.9 20 Gy; +20.2±3.6 14 Gy; P=0.02 vs 20 Gy wt; Figure). No significant differences between XRT wt vs KO mice were found in the LVPSP and LVEDP (Figure) or in the +dP/dT and -dP/dT (all P=ns). Survival rate was not different in XRT wt and KO mice (14 Gy, 100% wt and 100% KO; 20Gy, 83% wt and 57% KO; all P=ns).
Conclusions: The mouse lacking the IL-1 receptor shows preservation of contractile reserve 4 months after thoracic irradiation, but not an improvement in contractility at rest and diastolic function, nor an improvement in survival. This suggests an involvement of IL-1 signaling in some but not all the aspects of the XRT-induced cardiomyopathy.
- © 2013 by American Heart Association, Inc.