The left ventricular stress-velocity relation in transgenic mice expressing a dominant negative CREB transgene in the heart.
OBJECTIVE
CREB(A133) transgenic mice that express a dominant negative CREB transcription factor in cardiomyocytes develop a dilated cardiomyopathy that is anatomically, physiologically, and clinically similar to human idiopathic dilated cardiomyopathy. The goals of this study were to quantitate left ventricular (LV) contractility and measure cardiac reserve in CREB(A133) mice by using the relation of end-systolic wall stress to the velocity of fiber shortening.


METHODS
A total of 37 adult CD-1 mice (including both nontransgenic and CREB(A133) transgenic mice) were studied with simultaneously acquired high-fidelity instantaneous aortic pressures and 2-dimensionally targeted M-mode echocardiograms.


RESULTS
CREB(A133) mice displayed significantly lower values of LV fiber shortening velocities over a wide range of afterloads, and they displayed smaller dobutamine-induced shifts from baseline contractility relations. Counterbalancing effects of differences in LV geometry and aortic pressures resulted in comparable levels of LV wall stress during ejection in both groups.


CONCLUSIONS
These results demonstrate directly that CREB(A133) mice display reduced LV contractility at baseline and decreased cardiac reserve.
Department of Medicine, University of Chicago, Illinois, USA.
R C
RC
Fentzke
C E
CE
Korcarz
S G
SG
Shroff
H
H
Lin
J M
JM
Leiden
R M
RM
Lang
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D004452:Echocardiography; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D012044:Regression Analysis; D016277:Ventricular Function, Left / Q000502:physiology*