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J Thorac Cardiovasc Surg 1998;115:960-961
© 1998 Mosby, Inc.


LETTERS TO THE EDITOR

Should the anticalcification effect of epoxy compound in vascular bioprostheses be judged after implantation in mongrel dogs?

Yoshikazu Goto, MD

To the Editor:

I read with great interest the recently published article by Ichikawa and colleaguesGo 1 on use of polyepoxy compound–treated bovine jugular vein graft for reconstruction of right ventricular outflow tract in mongrel dogs. The authors have reported that the explanted conduits maintained their original shape, softness, and pliability with good coaptation of valves, without calcification or degenerative changes 1 year after implantation in dogs. I congratulate them for their development of a wonderful substitute for a valved conduit. However, clarification of certain points would be highly appreciated.

Why have the authors chosen dogs instead of sheep for their experimental model? Although there was mild-to-moderate calcification of glutaraldehyde-treated porcine aortic noncoronary cusps implanted in pulmonary circulation of dogs for 5 months,Go 2 there were no calcific changes of glutaraldehyde cross-linked valved conduits implanted in the systemic circulation of mongrel dogs.Go 3 The dog is not generally considered to be a useful model for accelerated calcification.Go 4 Glutaraldehyde-treated ovine collagen conduits did not calcify even by 3 years when implanted in dogs.Go 5 A valid conclusion with the merit of any anticalcification technique in any bioprostheses warrants implantation of the graft in juvenile sheep.Go 6

It is difficult to understand whether there is any chemical reaction between the fresh tissue and protamine. If so, the basic mechanism of the chemical reaction should be mentioned. From the discussion it is quite unclear how the authors prevent the slow release of protamine from the graft after implantation if no covalent bonding was established. Did protamine still remain after cross-linking in epoxy compound? If so, how could the protamine-bonded heparin interfere with the coagulation status of the conduit?

It should be kept in mind that the agents effective in prevention of calcification of bioprosthetic valve leaflets are not equally effective in prevention of aortic wall calcification.Go Go 7,8 The polyepoxy compound–treated homologous aorta (calcium = 151.51 ± 27.06 mg/gm, Fig. 1) calcifies more extensively than the fresh aorta (calcium = 128.93 ± 17.41 mg/gm) when implanted subcutaneously in weanling rats for 5 months; in addition, coupling (covalently) of heparin is completely ineffective when considering the calcification of polyepoxy compound–treated porcine and bovine jugular veins and rabbit and rat aortas (personal communication with Dr. Jyotirmay Chanda, March 2, 1997).



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Fig. 1. Calcification profile of polyepoxy compound–treated homologous aorta implanted subcutaneously in weanling rats for 5 months. Massive calcific deposits (black) along the elastin fibers of the aorta can be noticed. (von Kossa stain; original magnification x 50.)

 
Every cardiovascular surgeon is aware of the complications associated with currently available valved conduits. The need for a biocompatible valved conduit for repair of congenital heart defects is obvious. In my opinion, one should be cautious in planning experiments and interpreting any positive result concerning new anticalcification techniques in vascular bioprostheses.

Department of Cardiovascular SurgeryAkita University School of MedicineAkita 010, Japan12/8/87680

References

  1. Ichikawa Y, Noishiki Y, Kosuge T, Yamamoto K, Kondo J, Matsumoto A. Use of a bovine jugular vein graft with natural valve for right ventricular outflow tract reconstruction: a one-year animal study. J Thorac Cardiovasc Surg 1997;114:224-33.[Abstract/Free Full Text]
  2. Kuribayashi R, Chanda J, Abe T. Efficacy of the chitosan posttreatment in calcification prevention of the glutaraldehyde treated porcine aortic noncoronary cusp implanted in the right ventricular outflow tract in dogs. Artif Organs 1996;20:761-6.[Medline]
  3. Chanda J, Kuribayashi R, Abe T, Sekine S, Shibata S, Yamagishi I. Is the dog a useful model for accelerated calcification study of cardiovascular bioprostheses? Artif Organs 1997;21:391-5.
  4. Shemin RJ, Schoen FJ, Hein R, Austin J, Cohn LH. Hemodynamic and pathologic evaluation of a unileaflet pericardial bioprosthetic valve. J Thorac Cardiovasc Surg 1988;95:912-9.[Abstract]
  5. Ketharnathan V, Christie BA. Glutaraldehyde-tanned ovine collagen conduits as vascular xenografts in dogs. Arch Surg 1980;115:967-9.[Abstract]
  6. Chanda J, Kuribayashi R, Abe T. Valved conduit in the descending thoracic aorta in juvenile sheep: a useful, cost-effective model for accelerated calcification study in systemic circulation. Biomaterials 1997;18:1317-21.[Medline]
  7. Vyavahare N, Hirsch D, Lerner E, et al. Prevention of bioprosthetic heart valve calcification by ethanol preincubation: efficacy and mechanisms. Circulation 1997;95:479-88.[Abstract/Free Full Text]
  8. Chanda J, Kuribayashi R, Abe T. New-generation valved conduit: an experimental study. J Thorac Cardiovasc Surg 1997;114:218-23.[Abstract/Free Full Text]




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