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Ann Thorac Surg 1998;65:1726-1729
© 1998 The Society of Thoracic Surgeons

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Original articles: cardiovascular

Pulmonary Root Replacement With the Freestyle Stentless Aortic Xenograft in Growing Pigs

^a Department of Cardiac Surgery, University Hospital Leiden, Leiden, the Netherlands
^b Department of Pathology, University Hospital Leiden, Leiden, the Netherlands

Accepted for publication December 4, 1997.

Address reprint requests to Dr Schoof, Department of Cardiac Surgery, University Hospital Leiden, PO Box 9600, 2300 RC Leiden, the Netherlands
e-mail: (PSchoof{at}thorax.azl.nl)

This paper has been presented at the Second International Symposium on Stentless Bioprostheses, Noordwijk, the Netherlands, April 11–12, 1997.

	Abstract

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
Background. The stentless xenograft with its favorable hemodynamic performance on the left side of the heart seems an attractive, readily available alternative for the reconstruction of the right ventricular outflow tract in children.

Methods. To assess its function in a preclinical animal investigation, we replaced the pulmonary root with a Freestyle stentless aortic xenograft in 18 piglets of 26.6 ± 3.2 kg weight. The animals were allowed to grow as much as possible and slaughtered when symptoms of heart failure developed or body weight reached more than 160 kg. All valve explants were analyzed by gross examination and photography and, in 4 representative pigs, by histologic examination.

Results. Fourteen animals died prematurely after 2 weeks to 11 months. Twelve xenograft explants showed thick, immobilized, large nodular structures as cuspal remnants causing significant stenosis. At microscopy, large cuspal masses of degenerating collagen and fibrin and various inflammatory cells were frequently found. In the growing pig, most of the xenografts implanted in the pulmonary position showed early degeneration causing severe stenosis.

Conclusions. Use of this valve for right ventricular outflow tract reconstruction in children cannot be recommended.

	Introduction

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
Reconstruction of the right ventricular outflow tract for congenital cardiac defects, including the Ross operation, is generally performed with the use of a homograft. Its limited availability, however, keeps us searching for a readily available alternative with comparable hemodynamic characteristics and longevity. The stentless aortic xenograft with its superior hemodynamics and expected favorable durability appears a promising substitute [1–3]. Before embarking on clinical use for right ventricular outflow reconstruction, we decided to assess the valve in the growing pig, in which the results of left-sided implantation have shown to produce representative results [4].

	Material and methods

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
During a consecutive period of 15 months, 18 Dutch Landrace piglets weighing 26.6 ± 3.2 kg (mean ± standard deviation; range, 22.0 to 31.2 kg) were operated on. Pulmonary root replacement with the Medtronic Freestyle aortic root bioprosthesis (Medtronic, Minneapolis, MN) was performed in all 18 animals, 4 of whom had a Ross operation.

After overnight fasting, premedication, shaving, and weighing, anesthesia was induced and endotracheal intubation performed. Through a median sternotomy, the aorta and right atrium were cannulated and normothermic cardiopulmonary bypass was initiated. Cardioplegic arrest was induced using antegrade St. Thomas crystalloid cardioplegia. The pulmonary root was excised from the bifurcation up to and including a 5-mm muscular ridge below the valve. Subsequently, an oversized 21-mm (n = 13) or 23-mm (n = 5) stentless xenograft was tailored obliquely at its distal end to accommodate for the natural pulmonary artery curvature and was positioned with the coronary stumps pointing sideward. Both distal and proximal anastomoses were made with 5/0 Prolene (Ethicon, Somerville, NJ) in a continuous fashion. In 4 piglets, the pulmonary autograft was used to replace the aortic root. At normothermia, cardiopulmonary bypass was discontinued, the heart decannulated, heparin antagonized, and the chest closed leaving drains in the pericardium and substernally.

Postoperative course
All animals were extubated primarily or within a few hours after the operation and brought to a temperature- and oxygen-regulated intensive care unit. Core temperature and electrocardiogram were monitored, chest drains were intermittently aspirated, and arterial blood gases sampled. Anesthetics were administered and blood transfusions or diuretics were given if necessary. After 1 or 2 days, the animals returned to their stalls. Jugular and carotid lines as well as skin sutures were removed after 1 week using light general anesthesia. All animals stayed for 2 to 3 weeks before they were returned to the farm where they were aimed to grow as much as possible and fed unrestrictedly.

Throughout the entire study period, all animals received humane care in compliance with the "Dutch Animal Welfare Act." The experimental protocol was reviewed and approved by the University of Leiden Committee on the Care and Use of Laboratory Animals.

Euthanasia
Animals not dying of a natural cause were put to death when symptoms of heart failure developed or when they reached more than 160 kg. Euthanasia was carried out with the use of metomidate hydrochloride, azaperone, pancuronium, and potassium chloride.

Autopsy
In all animals, we performed a thoracolaparotomy and tried to establish a cause of death. The heart and proximal great vessels were excised and after inspection of the transected ventricles, the xenograft was excised, rinsed in Ringer’s solution, and photographed. All specimens were fixed in 3.6% formaldehyde and representative specimens (n = 4) were sectioned and stained (hematoxylin and eosin, elastin van Gieson, Gram). Stained sections were assessed by our histopathologist (Dr Han H. van Krieken).

	Results

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
There were no operative deaths. Early death occurred in 1 pig that accidentally pulled out its carotid line during the night and exsanguinated.

Three pigs were well at more than 160 kg and were sacrificed. Fourteen pigs died or were euthanized prematurely because of heart failure after 2 weeks to 11 months (Fig 1).

View larger version (12K): [in this window] [in a new window]   Fig 1. Cumulative (Cum) survival of the studied animals after operation. Three animals that were healthy at euthanasia were censored.

In the other 12 animals, more or less pronounced signs of right ventricular failure were found at autopsy, with hepatomegaly, ascites, and edematous tissues. All xenograft explants showed severe gross cuspal pathology with large, smooth, and thick immobilizing nodular structures representing the remnants of former cusps. The functional orifice was significantly reduced in all pigs (Fig 2). The tubular portion of the xenograft felt calcified in most explants and showed a smooth and shiny inner surface in all. Death and severe heart failure was supposed to be valve related in all 14 animals.

View larger version (122K): [in this window] [in a new window]   Fig 2. Macroscopic photograph of explanted xenograft showing the typical deformations of the valve as found in most animals.

At microscopy, large cuspal masses of degenerating collagen and fibrin were found with focal calcifications and nodules of various inflammatory cells but without microorganisms (Fig 3). In two explants, solitary colonies of bacteria were found within the collagen-fibrin nodules, without inflammatory cells.

View larger version (137K): [in this window] [in a new window]   Fig 3. Hematoxylin- and eosin-stained section showing the prosthetic wall (left) and the severely malformed valve (right) with large areas of collagen and fibrin. (x10 before 55% reduction.)

	Comment

Top Footnotes Abstract Introduction Material and methods Results Comment References

Because the Freestyle stentless xenograft has been shown to perform well in the aortic position in growing Dutch Landrace pigs [4], the mechanism of early degeneration in the pulmonary position is probably determined by the different hemodynamics in the right ventricular outflow tract and the intrinsic characteristics of the aortic xenograft valve. The reduced extensibility of the valve cusps due to glutaraldehyde fixation, without influence in the high pressures of the left ventricular outflow tract, may play a critical role in the lower pressures of the right ventricular outflow tract. It may cause an unfavorable opening–closing behavior of the valve, accelerating valve dysfunction due to platelet–fibrin depositions and subsequent cuspal immobilization and degeneration. The gross architecture of the xenograft explants differed markedly from homograft explants used as fresh implants for Ross operations in piglets of comparable weight and same species. The explants (n = 12) showed mild cuspal thickening and retraction with fine, probably calcific, nodular structures causing valve insufficiency and little or no wall calcification after 3 to 11 months (6.6 ± 2.3 months, mean ± standard deviation) (Schoof P et al, unpublished results).

The mode of degeneration of the xenograft explants was unfamiliar to us with various inflammatory cells found at microscopy, as a possible expression of a nonbacterial thrombotic endocarditis. An infectious cause could not be excluded in two of four samples because small colonies of bacteria were found, although without inflammatory cells.

Possibly the stentless pulmonary xenograft will be a better valve for pulmonary reconstruction. It might approach the hemodynamic performance and longevity of the pulmonary homograft. The theoretical advantages of the pulmonary over the aortic xenograft have already been alluded to by Donald Ross [10] and the superior function of fixed pulmonary valves was also suggested by Christie and Barratt-Boyes [11]. They showed that the glutaraldehyde-fixed pulmonary valve has the advantage of decreased stiffness, increased radial extensibility, and better preserved anisotropy probably due to a significantly lower collagen content [11]. These characteristics may be of particular benefit in the low pressure pulmonary position because the fixed pulmonary leaflets can be expected to offer significantly less hemodynamic resistance to blood flow, which possibly prevents the valve from early failure.

In conclusion, the Freestyle stentless aortic xenograft implanted in the pulmonary position in piglets showed early failure in the majority of animals. Presuming the juvenile pig to be a representative experimental model, clinical use of this valve in children would not be recommended.

	Footnotes

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
The Department of Research and Development of Medtronic Incorporated, Minneapolis, MN, is greatfully acknowledged for financial support of this study.

	References

Top Footnotes Abstract Introduction Material and methods Results Comment References

 

1. Westaby S., Amarasena N., Long V., et al. Time related hemodynamic changes after aortic replacement with the Freestyle stentless xenograft. Ann Thorac Surg 1995;60:1633-1639.[Abstract/Free Full Text]
2. Sintek C.F., Fletcher A.D., Khonsari S. Stentless porcine aortic root: valve of choice for the elderly patient with small aortic root?. J Thorac Cardiovasc Sug 1995;109:871-876.[Abstract]
3. Stelzer P, McCabe JC, Subramanian VA. Aortic valve replacement with the stentless porcine aortic root [Abstract]. 6th International Symposium on Cardiac Bioprostheses. Vancouver, BC, Canada, July 29–31, 1994.
4. Hazekamp M.G., Goffin Y.A., Huysmans H.A. The value of the stentless biovalve prosthesis. An experimental study. Eur J Cardiothorac Surg 1993;7:514-519.[Abstract]
5. Bisset G.S., Schwartz D.C., Benzing G., Helmsworth J.A., Schreiber J.T., Kaplan S. Late results of reconstruction of right ventricular outflow tract with porcine xenografts in children. Ann Thorac Surg 1981;31:437-443.[Abstract]
6. Ebert P.A. Current techniques and results in infancy. In: Moulton A.L., ed. Congenital heart surgery. Current techniques and controversies. Pasadena, CA: Appleton Davies, 1984:81-90.
7. Boyce S.W., Turley K., Yee E.S., Verrier E.D., Ebert P.A. The fate of the 12-mm porcine valved conduit from the right ventricle to the pulmonary artery. A ten-year experience. J Thorac Cardiovasc Surg 1988;95:201-207.[Abstract]
8. Schaff H.V., Di Donato R.M., Danielson G.K., et al. Reoperation for obstructed pulmonary ventricle–pulmonary artery conduits: early and late results. J Thorac Cardiovasc Surg 1984;88:334-343.[Abstract]
9. Konertz W., Sidiropoulos A., Hotz H., Borges A., Baumann G. Ross operation and right ventricular outflow tract reconstruction with stentless xenografts. J Heart Valve Dis 1996;5:418-420.[Medline]
10. Ross D.N. From homograft to stentless bioprosthesis. In: Piwnica A., Westaby S., eds. Stentless bioprostheses. Oxford: Isis Medical Media Ltd, 1995:21-23.
11. Christie G.W., Barratt-Boyes B.G. Mechanical properties of porcine pulmonary valve leaflets: how do they differ from aortic leaflets?. Ann Thorac Surg 1995;60:S195-S199.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Paul H. Schoof Mark G. Hazekamp Hans A. Huysmans Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schoof, P. H. Articles by Huysmans, H. A. Search for Related Content PubMed PubMed Citation Articles by Schoof, P. H. Articles by Huysmans, H. A.