Cory V Noel1, Nino Rainusso2,3, Matthew Robertson3, Jonathan Romero4, Prakash Masand5, Cristian Coarfa3,6, Robia Pautler4. 1. Pediatric Cardiology of Alaska, Seattle Children's Hospital - Division of Pediatric Cardiology, Anchorage, AK, USA. Cory.noel@seattlechildrens.org. 2. Division of Pediatric Hematology and Oncology, Baylor College of Medicine, Houston, USA. 3. Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, USA. 4. Baylor College of Medicine Small Animal Imaging Facility, Houston, USA. 5. Texas Children's Hospital Pediatric Radiology, Houston, USA. 6. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA.
Abstract
BACKGROUND: Cancer therapy-related cardiac dysfunction may occur in pediatric cancer survivors. Identification of early markers of myocardial damage secondary to anthracycline exposure is crucial to develop strategies that may ameliorate this complication. OBJECTIVES: The purpose of this study was to identify early myocardial changes induced by doxorubicin with and without cardioprotection using dexrazoxane detected by serial cardiac magnetic resonance imaging (CMR) in a pre-clinical mouse model. METHODS: Serial CMR examinations were performed in 90 mice distributed in 3 groups: 45 received doxorubicin (DOX group), 30 mice received doxorubicin with dexrazoxane (DOX/DEX group) and 15 mice received saline injections (control group). We obtained the following CMR parameters in all mice: T2, extracellular volume quantification (ECV), myocardial deformation, and functional quantification. RESULTS: Myocardial edema assessed by T2 time was the earliest parameter demonstrating evidence of myocardial injury, most notable in the DOX group at week 4 and 8 compared with DOX/DEX group. Similarly, global longitudinal strain was abnormal in both the DOX and DOX/DEX groups. However, this change persisted only in the DOX group. The ECV was significantly elevated in the DOX group at the final CMR, while only minimally elevated in the DOX/DEX group. The right and left ejection fraction was decreased, along with the mass to volume ratio in the DOX group. The T2 time, ECV, and deformation correlated with ejection fraction and left ventricular volume. CONCLUSIONS: T2 time and deformation by CMR identifies early myocardial injury from anthracyclines. Dexrazoxne did not prevent the initial edema, but the inflammatory changes were not sustained. CMR may be useful for early detection of cardiac dysfunction. Serial CMR demonstrates dexrazoxane minimizes cardiac dysfunction and aids recovery in a mouse model.
BACKGROUND:Cancer therapy-related cardiac dysfunction may occur in pediatric cancer survivors. Identification of early markers of myocardial damage secondary to anthracycline exposure is crucial to develop strategies that may ameliorate this complication. OBJECTIVES: The purpose of this study was to identify early myocardial changes induced by doxorubicin with and without cardioprotection using dexrazoxane detected by serial cardiac magnetic resonance imaging (CMR) in a pre-clinical mouse model. METHODS: Serial CMR examinations were performed in 90 mice distributed in 3 groups: 45 received doxorubicin (DOX group), 30 mice received doxorubicin with dexrazoxane (DOX/DEX group) and 15 mice received saline injections (control group). We obtained the following CMR parameters in all mice: T2, extracellular volume quantification (ECV), myocardial deformation, and functional quantification. RESULTS:Myocardial edema assessed by T2 time was the earliest parameter demonstrating evidence of myocardial injury, most notable in the DOX group at week 4 and 8 compared with DOX/DEX group. Similarly, global longitudinal strain was abnormal in both the DOX and DOX/DEX groups. However, this change persisted only in the DOX group. The ECV was significantly elevated in the DOX group at the final CMR, while only minimally elevated in the DOX/DEX group. The right and left ejection fraction was decreased, along with the mass to volume ratio in the DOX group. The T2 time, ECV, and deformation correlated with ejection fraction and left ventricular volume. CONCLUSIONS: T2 time and deformation by CMR identifies early myocardial injury from anthracyclines. Dexrazoxne did not prevent the initial edema, but the inflammatory changes were not sustained. CMR may be useful for early detection of cardiac dysfunction. Serial CMR demonstrates dexrazoxane minimizes cardiac dysfunction and aids recovery in a mouse model.
Entities:
Keywords:
Anthracycline; Cardiac MRI; Cardiotoxicity; Dexrazoxane; Early detection; Pre-clinical
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