M. Scheuermann-freestone et al., A new model of congestive heart failure in the mouse due to chronic volumeoverload, EUR J HE FA, 3(5), 2001, pp. 535-543
Objective: Recently, deletion of specific genes by so called knock-out tech
niques has become important for investigating the pathogenesis of various d
iseases. This form of genetic engineering is widely performed in murine mod
els. There are, however, only a limited number of mouse models available in
cardiovascular pathology. The objective of this study, therefore, was to d
evelop a new model of overt congestive heart failure associated with myocar
dial hypertrophy in the mouse. Methods: Female C57/BL6 mice weighing 19-20
g were anesthetized with ether. After abdominal incision, the aorta was tem
porarily clamped proximal to the renal arteries. The aorta was then punctur
ed with a needle (outer diameter 0.6 mm) and the needle was further advance
d into the adjacent vena cava. After withdrawal of the needle, the aortic p
uncture site was sealed with cyanoacrylate glue. The clamp was removed, and
the patency of the shunt was visually verified as swelling and mixing of v
enous and arterial blood in the vena cava. Sham-operated mice served as con
trols. Results: Perioperative mortality of mice with aortocaval shunt was 4
2%. Four weeks after shunt induction, mice showed a significant cardiac hyp
ertrophy with a relative heart weight of 7.5 +/- 0.2 mg/100 g body weight (
vs. 5.1 +/- 0.7 mg/100 g in control mice, P < 0.001). While no changes in b
lood pressure and heart rate occurred, left ventricular enddiastolic pressu
re was significantly increased in mice with shunt, and left ventricular con
tractility was impaired from 6331 +/- 412 to 4170 +/- 296 mmHg/s (P < 0.05)
. Plasma concentrations of atrial natriuretic peptide (ANP) and its second
messenger cGMP as humoral markers of heart failure as well as ventricular e
xpression of ANP- and brain natriuretic peptide (BNP)-mRNA were significant
ly increased in mice with shunt compared to control mice. Conclusions: The
aortocaval shunt in the mouse constitutes a new model of overt congestive h
eart failure with impaired hemodynamic parameters and may be a useful tool
to investigate the role of particular genes in the development of heart fai
lure. (C) 2001 European Society of Cardiology. All rights reserved.