The left ventricular stress-velocity relation in transgenic mice expressing a dominant negative CREB transgene in the heart

Objective: CREBA133 transgenic mice that express a dominant negative CREB t ranscription factor in cardiomyocytes develop a dilated cardiomyopathy that is anatomically, physiologically, and clinically similar to human idiopath ic dilated cardiomyopathy. The goals of this study were to quantitate left ventricular (LV) contractility and measure cardiac reserve in CREBA133 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 CR EBA133 transgenic mice) were studied with simultaneously acquired high-fide lity instantaneous aortic pressures and 2-dimensionally targeted M-mode ech ocardiograms. Results: CREBA133 mice displayed significantly lower values of LV fiber sho rtening velocities over a wide range of afterloads, and they displayed smal ler dobutamine-induced shifts from baseline contractility relations. Counte rbalancing effects of differences in LV geometry and aortic pressures resul ted in comparable levels of LV wall stress during ejection in both groups. Conclusion: These results demonstrate directly that CREBA133 mice display r educed LV contractility at baseline and decreased cardiac reserve.