| Abstrakt: |
Introduction:Use of angiotensin converting enzyme inhibitors (ACEi) for the primary prevention of anthracycline cardiomyopathy (ACM) remains controversial. Prior clinical studies use isolated measures of cardiac function with short term follow up. Cardiac MRI (CMR) robustly characterizes myocardial tissue, and may quantify the effects of a primary prevention ACEi strategy.Purpose:We performed a pilot study to determine the feasibility of serial CMR to identify treatment effects of ACEi in a murine ACM model.Methods:Female BL6 mice (N=5/group) underwent 5 week induction with intraperitoneal doxorubicin injection 5mg/kg/wk (DOX), DOX + concurrent oral captopril for 5 weeks (EARLY), DOX + captopril for weeks 5-10 (LATE), or saline injection for 5 weeks (SHAM). CMR was performed on a Bruker 7T MRI using Intragate phase-gating at baseline (BL), 5, and 10 weeks. Image processing was performed using Circle-CVI42.Results:We observed equivalent 10-week survival in the DOX, EARLY and SHAM mice, all LATE mice died before 10 weeks (60% vs 0%, p<0.05). In surviving mice (N=3/group), no difference was observed in LVEF, end diastolic volume (EDV), myocardial mass (MM) or LV strain (2-factor ANOVA, p>0.2). However, there was a trend toward reduction of LVEF during induction in DOX and EARLY mice v. SHAM (-6% v. -12% v. 0.1% p=0.6), and EF improvement at 5 to 10 weeks in all mice (7%, v. 16% v. 1.4% p= 0.5). Similarly, EDV decreased during induction in the DOX and EARLY mice v. SHAM (-2.3 v.-8.6 v. 4.1 uL, p=0.3), with continued reduction at 5 to 10 weeks in DOX and increase in EARLY and SHAM mice (-1.6 v. 9.6 v. 2.2 uL, p= 0.3). MM decreased during induction in DOX and EARLY mice v. SHAM (-8 v. -18 v. -3 mg, p=0.04) with recovery at 5-10 weeks in EARLY mice similar to SHAM (-0.2 v. 16 v. 14 mg, p=0.02). We identified a trend toward improved LV radial, circumferential and longitudinal strain in EARLY mice during weeks 5-10. Changes in LV torsion were not significant (p=0.8).Conclusions:Serial CMR is a feasible method to assess murine ACM, however dose adjustments and increased sample sizes are necessary in further experiments. Delayed treatment with ACEi in mice was associated with increased mortality whereas early treatment appears to ameliorate the late adverse cardiac effects of ACM. |
