Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury.
OBJECTIVE
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.


RESULTS
TDI-derived peak endocardial systolic velocity (V(ENDO)) 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. V(ENDO) 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 V(ENDO) and SR correlated with the decrease in dP/dt(MAX), and the change in V(ENDO) 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.


CONCLUSIONS
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.
Neilan
Tomas G
TG
Cardiac Ultrasound Laboratory, Cardiology Division of the Department of Medicine, Harvard Medical School, USA.
Jassal
Davinder S
DS
Perez-Sanz
Teresa M
TM
Raher
Michael J
MJ
Pradhan
Aruna D
AD
Buys
Emmanuel S
ES
Ichinose
Fumito
F
Bayne
David B
DB
Halpern
Elkan F
EF
Weyman
Arthur E
AE
Derumeaux
Geneviéve
G
Bloch
Kenneth D
KD
Picard
Michael H
MH
Scherrer-Crosbie
Marielle
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D017209:Apoptosis; D001794:Blood Pressure / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects; D015150:Echocardiography, Doppler; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D013318:Stroke Volume / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000401:mortality
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin