European Heart Journal Advance Access published online on May 22, 2006
European Heart Journal, doi:10.1093/eurheartj/ehl013
1 Cardiac Ultrasound Laboratory, Harvard Medical School, USA; Cardiovascular Research Center, Cardiology Division of the Department of Medicine, Harvard Medical School, USA
* To whom correspondence should be addressed. Aims Currently available non-invasive imaging methods frequently fail to detect alterations in left ventricular (LV) function despite histological evidence of injury. Tissue Doppler imaging (TDI) can detect subtle LV dysfunction. The aim of this study was to investigate whether TDI indices can predict LV systolic dysfunction and mortality following exposure to doxorubicin (DOX) in mice. Methods and results TDI-derived peak endocardial systolic velocity (VENDO) and strain rate (SR), as well as M-mode and two-dimensional indices of LV systolic function, were measured serially in mice after receiving DOX as a single dose (20 mg/kg). Haemodynamic measurements were obtained invasively before and at 1, 2, 4, and 5 days after the single DOX dose. Cardiac apoptosis was measured before and at 1 day after DOX. VENDO and SR decreased after 1 and 2 days, respectively, whereas changes in fractional shortening (FS) and LV ejection fraction (LVEF) were not detected before 5 days. The reduction in both VENDO and SR correlated with the decrease in dP/dtMAX, and the change in VENDO correlated with the early increase in cardiac cell apoptosis. In a subsequent experiment, DOX was administered at 4 mg/kg/week for 5 weeks, and LV function was followed serially for 16 weeks. In this chronic experiment, TDI indices decreased before FS and LVEF, correlated with late LV dysfunction, and predicted DOX-induced mortality. Conclusion In a murine model of DOX-induced cardiac injury, TDI detects LV dysfunction prior to alterations in conventional echocardiographic indices and predicts mortality. This study suggests that TDI may be a reliable tool to detect early subtle changes in DOX-induced cardiac dysfunction.
Received October 17, 2005
Revised April 7, 2006
Accepted April 13, 2006
Preclinical research
Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury
Tomas G. Neilan 1,
Davinder S. Jassal 2,
Teresa M. Perez-Sanz 2,
Michael J. Raher 3,
Aruna D. Pradhan 4,
Emmanuel S. Buys 3,
Fumito Ichinose 3,
David B. Bayne 3,
Elkan F. Halpern 5,
Arthur E. Weyman 2,
Geneviéve Derumeaux 6,
Kenneth D. Bloch 3,
Michael H. Picard 2,
and
Marielle Scherrer-Crosbie 1 *
2 Cardiac Ultrasound Laboratory, Harvard Medical School, USA
3 Cardiovascular Research Center, Cardiology Division of the Department of Medicine, Harvard Medical School, USA
4 Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, USA
5 Institute for Technology Assessment, Massachusetts General Hospital, USA
6 Department of Cardiology, Hospital Louis Pradel, Lyon, France
Marielle Scherrer-Crosbie, E-mail: marielle{at}crosbie.com
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