Characterization of a model to independently study regression of ventricular hypertrophy.
BACKGROUND
Although a host of studies catalogue changes that occur with the development of left ventricular hypertrophy (LVH), there is little information about features related solely to LVH regression. This is due, in part, to a lack of animal models to study this question. While traditional models of aortic banding have provided useful information regarding the development of LVH, a similarly effective model is necessary to study mechanisms associated with LVH regression.


METHODS
Minimally invasive transverse arch banding was performed in C57BL6 mice using a slipknot technique. Twenty-eight days later, the band was removed. Carotid Doppler velocity gradients were serially measured to assess the degree of aortic constriction. Echocardiography, histology, electron microscopy, and real-time polymerase chain reaction were used to assess functional, structural, and genetic aspects of hypertrophy.


RESULTS
Banding of the transverse arch created the expected increase in aortic velocity and gradient between the left and right carotid artery, which normalized with relief of the constriction. Pressure overload resulted in a robust hypertrophic response as assessed by heart weight/body weight ratios, gross and microscopic histology, transthoracic echocardiography, electron microscopy, and hypertrophy gene expression. These markers were reversed within 1 week following debanding and were maintained for up to 4 weeks. Mortality rate for the cumulative procedure was 5% over a 2-month period.


CONCLUSIONS
These results demonstrate a safe, effective, and reproducible method of promoting LVH regression-avoiding the need for endotracheal intubation, mechanical ventilation, and a second invasive surgery to remove the constriction. The simplicity of this technique combined with the well-known advantages of using the mouse species makes this model both unique and relevant. Ultimately, this model will facilitate focused study of independent mechanisms involved with LVH regression.
Stansfield
William E
WE
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Rojas
Mauricio
M
Corn
Drew
D
Willis
Monte
M
Patterson
Cam
C
Smyth
Susan S
SS
Selzman
Craig H
CH
D000818:Animals; D001013:Aorta, Thoracic; D001783:Blood Flow Velocity; D002339:Carotid Arteries; D004195:Disease Models, Animal; D004452:Echocardiography; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function; D015996:Survival Rate
D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain