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Ann Thorac Surg 2002;74:298-299
© 2002 The Society of Thoracic Surgeons


Correspondence

Successful cellular cardiomyoplasty in canine idiopathic dilated cardiomyopathy

Nicolas Borenstein, DVM, MSca, Valérie Chetboul, DVM, PhDa, Charissa Rajnoch, MScb, Patrick Bruneval, MD, PhDb, Alain Carpentier, MD, PhDb

a École Nationale Vétérinaire d’Alfort, 7 avenue du Général de Gaulle, 94704 Maisons-Alfort, France
b Laboratory of Cardiac Grafts and Prostheses, Broussais Hospital, 96 rue Didot, 75014 Paris, France

e-mail: nicolasborenstein{at}wanadoo.fr

To the Editor

The concept of myogenic cell transplantation into the myocardium, known as cellular cardiomyoplasty, is based on the contribution of exogenous cells to replace lost or altered cardiomyocytes to restore the functional performance of the heart. We read with great interest the article by Yoo and associates [1] that has directed attention to the potential benefit of smooth muscle cell transplantation in a small animal model of dilated cardiomyopathy (DCM). We know of only one other report [2] on the use of cellular cardiomyoplasty to treat idiopathic DCM.

Dilated cardiomyopathy is also a well-recognized cause of spontaneous heart failure in large- and giant-breed dogs. We took advantage of this to investigate the clinical and hemodynamic impact of cellular cardiomyoplasty on treating this pathological condition. In dogs, DCM has a poor prognosis with 1- and 2-year survival rates of 17.5% and 7.5%, respectively [3]. Clinical, hemodynamic, and histological findings have shown large-breed dogs to be a relevant clinical model for human cardiology [4].

Autologous intramyocardial skeletal muscle cell implantation was carried out in 5 dogs weighing 30 to 70 kg; these dogs were followed for 2 years. A skeletal muscle biopsy was performed in the sartorius muscle; the cell culture technique gave a yield of more than 93% myogenic cells after 10 days of propagation. Twenty epicardial injections into the left ventricle were performed with a total of 50 x 106 cells. Functional variables were evaluated by color Doppler echocardiography in all dogs and by thallium single photon emission computed tomography in 1 dog.

There were three deaths during the postoperative period. Two dogs died of intractable tachyarrhythmia on postoperative days 5 and 10, and 1 dog died of a documented pulmonary embolism on postoperative day 5. All 3 dogs were in severe heart failure before the operation. For the 2 dogs that survived the postoperative period, a marked improvement in clinical status was noted 4 months after implantation. At echocardiography, shortening fractions rose from 25% to 36% in 1 dog and from 20% to 28% in the other; systolic volumes indexed to body surface area decreased from 56.3 to 39.4 mL/m2 and from 67.8 to 48.1 mL/m2, respectively. Three weeks after implantation, thallium single photon emission computed tomography in 1 dog showed 50% recovery of myocardial viability in the apical zone. Echocardiographic variables slowly worsened over a 5-month period in 1 of the 2 surviving dogs. This dog was killed because of prostatic disease and deteriorating clinical status. Grafted cells could not be identified in the harvested heart. The other dog is still alive 2 years after implantation and is in New York Heart Association class I; shortening fraction is 25% versus 20% preoperatively.

Although most research teams have addressed the concept of cell implantation to treat ischemic heart disease and regional dysfunction, we believe that the results presented here in a large animal model show that DCM may also respond to skeletal muscle cell implantation. However, despite overall encouraging results, further research is warranted to elucidate how skeletal muscle cell implantation may improve ventricular pump performance.

Footnotes

Dr Borenstein received a grant from the French Académie Nationale de Médecine for this work.

References

  1. Yoo K.J., Li R.-K., Weisel R.D., Mickle D.A.G., Li G., Yau T.M. Autologous smooth muscle cell transplantation improved heart function in dilated cardiomyopathy. Ann Thorac Surg 2000;70:859-865.[Abstract/Full Text]
  2. Yoo K.J., Li R.-K., Weisel R.D., et al. Heart cell transplantation improves heart function in dilated cardiomyopathic hamsters. Circulation 2000;102(Suppl 3):204-209.
  3. Tidholm A., Svensson H., Sylven C. Survival and prognostic factors in 189 dogs with dilated cardiomyopathy. J Am Anim Hosp Assoc 1997;33:364-368.[Medline]
  4. Van Vleet J.F., Ferrans V.J., Weirich W.E. Pathologic alterations in congestive cardiomyopathy of dogs. Am J Vet Res 1981;42:416-424.[Medline]



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