title: Early detection of doxorubicin myocardial injury by ultrasonic tissue characterization in an experimental animal model.
abstract: In the clinical setting, the early detection of myocardial injury induced by doxorubicin (DXR) is still considered a challenge. To assess whether ultrasonic tissue characterization (UTC) can identify early DXR-related myocardial lesions and their correlation with collagen myocardial percentages, we studied 60 rats at basal status and prospectively after 2 mg/Kg/week DXR endovenous infusion. Echocardiographic examinations were conducted at baseline and at 8, 10, 12, 14 and 16 mg/Kg DXR cumulative dose. The left ventricle ejection fraction (LVEF), shortening fraction (SF), and the UTC indices: corrected coefficient of integrated backscatter (IBS) (tissue IBS intensity/ phantom IBS intensity) (CC-IBS) and the cyclic variation magnitude of this intensity curve (MCV) were measured. The variation of each parameter of study through DXR dose was expressed by the average and standard error at specific DXR dosages and those at baseline. The collagen percent (%) was calculated in six control group animals and 24 DXR group animals. CC-IBS increased (1.29±0.27 x 1.1±0.26-basal; p=0.005) and MCV decreased (9.1± 2.8 x 11.02±2.6-basal; p=0.006) from 8 mg/Kg to 16 mg/Kg DXR. LVEF presented only a slight but significant decrease (80.4±6.9% x 85.3±6.9%-basal, p=0.005) from 8 mg/Kg to 16 mg/Kg DXR. CC-IBS was 72.2% sensitive and 83.3% specific to detect collagen deposition of 4.24% (AUC=0.76). LVEF was not accurate to detect initial collagen deposition (AUC=0.54).
  
  
  CONCLUSIONS
  UTC was able to early identify the DXR myocardial lesion when compared to LVEF, showing good accuracy to detect the initial collagen deposition in this experimental animal model.
authors.affiliation: Division of Cardiology, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Minna Moreira Dias
authors.initials: MM
authors.lastname: Romano
authors.forename: Antônio
authors.initials: A
authors.lastname: Pazin-Filho
authors.forename: João Lucas
authors.initials: JL
authors.lastname: O'Connel
authors.forename: Marcus Vinícius
authors.initials: MV
authors.lastname: Simões
authors.forename: André
authors.initials: A
authors.lastname: Schmidt
authors.forename: Érica C
authors.initials: ÉC
authors.lastname: Campos
authors.forename: Marcos
authors.initials: M
authors.lastname: Rossi
authors.forename: Benedito Carlos
authors.initials: BC
authors.lastname: Maciel
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects*; D042241:Early Diagnosis; D006331:Heart Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D014463:Ultrasonography; D016277:Ventricular Function, Left
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin