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Cardiovascular Research 1998 37(1):236-238; doi:10.1016/S0008-6363(97)00219-8
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

A new heart failure model in rat by an end-to-side femoral vessel anastomosis

Cuneyt Ozeka, Feng Zhanga,b, William C Lineaweavera,*, Brian T Chinb, Thomas Eimanc, Leonard Newlinb and Harry J Bunckeb

aDivision of Plastic and Reconstructive Surgery, Stanford University Medical Center, NC 104, Stanford, CA 94305, USA
bMicrosurgical Replantation-Transplantation Service, Davies Medical Center, San Francisco, CA, USA
cDepartment of Pathology, Davies Medical Center, San Francisco, CA, USA

* Corresponding author. Tel. (+1-415) 723 5824; Fax: (+1-415) 725 6605.

Received 10 March 1997; accepted 25 August 1997


   Abstract
Top
 Abstract
1 Introduction
 2 Material and methods
 3 Results
 4 Discussion
 References
 
Objective: The aim of this study was to develop a new shunting procedure for producing heart failure in the rat incorporating microvascular techniques and avoiding an abdominal operation. Method: We performed an end-to-side anastomosis between the femoral vein and the femoral artery just proximal to their trifurcation into the saphenous, epigastric, and distal femoral vessels. Results: Of the 15 rats which underwent this procedure, six died within 48 h. The nine surviving animals were sacrificed and examined six weeks following surgery. All nine had developed cardiac hypertrophy and cardiac failure. Conclusion: This model provides a relatively simple and reproducible means of creating high output heart failure and cardiac hypertrophy in the rat without necessitating abdominal surgery.

KEYWORDS Microsurgery; Rat; Cardiac failure; Arteriovenous shunt


   1 Introduction
Top
 Abstract
 1 Introduction
2 Material and methods
 3 Results
 4 Discussion
 References
 
The rat is a useful experimental animal for investigating cardiac hypertrophy as well as the hemodynamic and endocrine aspects of chronic heart failure [1–7]. Two commonly used surgical methods of inducing heart failure in the rat are ligation of the left coronary artery [5, 6]and creation of a fistula between the vena cava and the abdominal aorta [1–4, 7]. The drawback of both of these operations is that they require an abdominal laporatomy or thoracotomy [1–7], which subjects the animals to additional stress and trauma. Further, dissections of the abdominal aorta and vena cava are time-consuming and difficult compared to dissection of the peripheral vessels. In this study, we present an easier method of developing heart failure in the rat with acceptable mortality rates and a 100% rate of heart failure development in survivors.


   2 Material and methods
Top
 Abstract
 1 Introduction
 2 Material and methods
3 Results
 4 Discussion
 References
 
We used 500–550 g adult Long-Evans rats. The National Research Council's guidelines for the use and care of laboratory animals were followed. The animals were anesthetized with 60 mg/kg intraperitoneal sodium pentobarbital injections.

In the 15 rats (average 516 g, Std 17.32) which comprised the experimental group, an end-to-side anastomosis was made between the femoral vein and the femoral artery just proximal to their trifurcation into the saphenous, epigastric, and distal femoral vessels. The distal segment of the transected femoral vein was anastomosed to femoral artery in an end to side fashion in order to increase the venous flow. The diameter of the anastomosis was 2 mm and ten 10.0 nylon sutures were used for anastomosis. Procedure took approximately 20 min. Another group of 15 animals (average 530 g, Std 14.85) without any operation comprised the control group. See Fig. 1.


Figure 1
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  		Fig. 1 A: Normal anatomy of the femoral vein and femoral artery. B: The procedure.

 
Six weeks following surgery, the patency of each shunt was verified by the milking test. The animals were then sacrificed, and the hearts were excised and fixed in 10% formalin. After 48 h of fixation, the hearts were weighed, histological sections were taken vertical to the mid point of the interventricular septum and the left ventricle diameter and wall thickness were measured. See Table 1.


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  		Table 1 Comparison of left ventricular diameter and wall thickness values between A–V shunted and control groups

 

   3 Results
Top
 Abstract
 1 Introduction
 2 Material and methods
 3 Results
4 Discussion
 References
 
Of the 15 rats in which an arteriovenous shunt was performed, six (40%) died within 48 h of surgery. The remaining nine (60%) rats had patent anastomoses and all these rats developed cardiac hypertrophy. During the 6th week observation and milking test1 the vein site was found to be dilated and pulsatile. The animals which received arteriovenous shunts had significantly heavier hearts than the normal control group. The left ventricle diameters and wall thickness were also significantly larger in the experimental group than in the control group. The measurements are shown below, and are expressed as means and standard deviation (STD). Significance was determined using the unpaired t test.


   4 Discussion
Top
 Abstract
 1 Introduction
 2 Material and methods
 3 Results
 4 Discussion
References
 
This technique permits creation of high output cardiac failure in the rat leg microsurgical creation of an arteriovenous fistula between peripheral vessels. The fistula itself can be strictly standardized (the diameter of the anastomosis was 2 mm and ten 10.0 nylon sutures were used for anastomosis) and cardiac failure and hypertrophy developed in all survivors. While left ventricle wall thickening indicated the cardiac hypertrophy, left ventricle dilatation indicated cardiac failure. We anticipate that this new technique will be useful for laboratories interested in investigating high output heart failure and cardiac hypertrophy.

Time for primary review 29 days.


   Acknowledgements
 
Support for this study was provided by the Microsurgery Foundation of the Davies Medical Center and Ege University, Izmir, Turkey.


   Notes
 
1 (The vessel is occluded with forceps distal to the anastomosis. Another forceps is placed just distal to the first and the vessel is milked for several mm away from the anastomosis. The emptied vessel is occluded at this point and the proximal forceps is released. Rapid filling is seen from proximal to distal) Back


   References
Top
 Abstract
 1 Introduction
 2 Material and methods
 3 Results
 4 Discussion
 References
 

  1. Flaim S.F., Minteer W.J., Nellis S.H., Clark D.P. Chronic arteriovenous shunt: evaluation of a model for heart failure in the rat. Am J Physiol (1979) 236:H698–H704.[Web of Science][Medline]
  2. Flaim S.F., Minteer W.J., Zelis R. Acute effects of arterio-venous shunt on cardiovascular hemodynamics in rat. Pflugers Arch (1980) 385:203–209.[CrossRef][Web of Science][Medline]
  3. Flaim SF, Minteer WJ. Ventricular volume overload alters cardiac output distribution in rats during exercise. J Appl Physiol 1980;49:482-490.
  4. Hatt P.Y., Rakusan K., Gastineau P., Laplace M. Morphometry and ultrastructure of heart hypertrophy induced by chronic volume overload (aorta-caval fistula in the rat). J Mol Cell Cardiol (1979) 11:989–998.[CrossRef][Web of Science][Medline]
  5. Mendez R.E., Pfeffer J.M., Ortola F.V. Atrial natriuretic peptide transcription, storage and release in rats with myocardial infarction. Am J Physiol (1987) 253:H1449–H1455.[Web of Science][Medline]
  6. Tsunoda K., Mendelshoh F.A.O., Sexton P.M., Chai S.Y., Hodsman G.P., Johnston C.I. Decreased atrial natriuretic peptide binding in renal medulla in rats with chronic heart failure. Circ Res (1988) 62:155–161.[Abstract/Free Full Text]
  7. Garcia R., Diebold S. Simple rapid, and effective method of producing aortacaval shunts in the rat. Cardiovasc Res (1990) 24:430–432.[Abstract/Free Full Text]

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