A new model of congestive heart failure in the mouse due to chronic volume overload.
OBJECTIVE
Recently, deletion of specific genes by so called knock-out techniques has become important for investigating the pathogenesis of various diseases. This form of genetic engineering is widely performed in murine models. There are, however, only a limited number of mouse models available in cardiovascular pathology. The objective of this study, therefore, was to develop a new model of overt congestive heart failure associated with myocardial hypertrophy in the mouse.


METHODS
Female C57/BL6 mice weighing 19-20 g were anesthetized with ether. After abdominal incision, the aorta was temporarily clamped proximal to the renal arteries. The aorta was then punctured with a needle (outer diameter 0.6 mm) and the needle was further advanced into the adjacent vena cava. After withdrawal of the needle, the aortic puncture site was sealed with cyanoacrylate glue. The clamp was removed, and the patency of the shunt was visually verified as swelling and mixing of venous and arterial blood in the vena cava. Sham-operated mice served as controls.


RESULTS
Perioperative mortality of mice with aortocaval shunt was 42%. Four weeks after shunt induction, mice showed a significant cardiac hypertrophy 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 blood pressure and heart rate occurred, left ventricular enddiastolic pressure was significantly increased in mice with shunt, and left ventricular contractility 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 expression of ANP- and brain natriuretic peptide (BNP)-mRNA were significantly increased in mice with shunt compared to control mice.


CONCLUSIONS
The aortocaval shunt in the mouse constitutes a new model of overt congestive heart failure with impaired hemodynamic parameters and may be a useful tool to investigate the role of particular genes in the development of heart failure.
Scheuermann-Freestone
M
M
Franz-Volhard Clinic, Laboratory of Clinical and Experimental Heart Failure, Max Delbrück Center for Molecular Medicine, Berlin, Germany. mscheuer@bioch.ox.ac.uk
Freestone
N S
NS
Langenickel
T
T
Höhnel
K
K
Dietz
R
R
Willenbrock
R
R
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002306:Cardiac Volume / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020097:Natriuretic Peptide, Brain / Q000378:metabolism
D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor