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CASE REPORT
DOHMEN ET AL
ENDOTHELIAL CELL-SEEDED BOVINE IMA
References
FEATURE ARTICLES
1. Laube HR, Duwe J, Rutsch W, Konertz W. Clinical experience
with autologous endothelial cell-seeded polytetrafluorethylene coronary artery bypass grafts. J Thorac Cardiovasc Surg
2000;120:134 – 41.
2. Tiwari A, Salacinski HJ, Hamilton G, Seifalian AM. Tissue
engineering of vascular bypass grafts: role of endothelial cell
extraction. Eur J Vasc Endovasc Surg 2001;21:193–201.
3. Kleisli T, Cheng W, Jacobs MJ, et al. In the current era,
complete revascularization improves survival after coronary
artery bypass surgery. J Thorac Cardiovasc Surg 2005;129:
1283–91.
4. Kouchoukos NT, Wareing TH, Murphy SF, Pelate C, Marshall
WG Jr. Risks of bilateral internal mammary artery bypass
grafting. Ann Thorac Surg 1990;49:210 –9.
5. Sajja LR, Mannam G, Pantula NR, Sompalli S. Role of radial
artery graft in coronary artery bypass grafting. Ann Thorac
Surg 2005;79:2180 – 8.
6. Hirose H, Amano A, Takanashi S, Takahashi A. Coronary
artery bypass grafting using the gastroepiploic artery: 1,000
cases. Ann Thorac Surg 2002;73:1371–9.
7. Herring M, Gardner A, Glover J. A single-staged technique for
seeding vascular grafts with autogenous endothelium. Surgery
1978;84:498–504.
8. Deutsch M, Meinhart J, Fischlein T, Preiss P, Zilla P. Clinical
autologous in vitro endothelialization of infrainguinal ePTFE grafts
in 100 patients: a 9-year experience. Surgery 1999;126:847–55.
9. Lembcke A, Hein PA, Dohmen PM, et al. Pictorial review:
electron beam computed tomography and multislice spiral
computed tomography for cardiac imaging. Eur J Radiol
2006;57:356 – 67.
Endothelial Cell-Seeded Bovine
Internal Mammary Artery for
Complete Revascularization
Pascal M. Dohmen, MD, PhD, Davide Gabbieri, MD,
Alexander Lembcke, MD, and
Wolfgang Konertz, MD, PhD
Department of Cardiovascular Surgery, Radiology, Charité
Hospital, Medical University Berlin, Berlin, Germany
We present a 79-year-old woman with coronary heart disease who underwent complete revascularization by using a
No-React bovine internal mammary artery seeded with
autologous endothelial cells. Her postoperative course
was uneventful, and the patient was recently in New
York Heart Association functional class I. Multislice
computed tomography imaging showed patent grafts at
20 months of follow-up.
(Ann Thorac Surg 2007;83:1168 –9)
© 2007 by The Society of Thoracic Surgeons
T
he lack of adequate autologous graft material during
coronary bypass surgery has forced surgeons to
evaluate alternative graft materials. Bovine internal mammary arteries were investigated many years ago with poor
results [1]. In a previous experiment, we were able to
Accepted for publication Aug 1, 2006.
Address correspondence to Dr Dohmen, Department of Cardiovascular
Surgery, Charité Hospital, Medical University Berlin, Luisenstrasse 13,
D-10117 Berlin; e-mail: [email protected].
© 2007 by The Society of Thoracic Surgeons
Published by Elsevier Inc
Ann Thorac Surg
2007;83:1168 –9
show that the No-React Shellhigh bovine internal mammary artery (NR-SIMA; Shellhigh Inc, Union, NJ) can be
seeded with endothelial cells [2]. This report evaluates
the implantation of a seeded NR-SIMA for complete
revascularization in a patient with angina pectoris.
A 79-year-old woman presented at our hospital with
angina pectoris. Her medical history included arterial
hypertension, peripheral arterial vascular disease,
esophageal reflux, and severe bilateral varicosis. Transthoracic echocardiography showed a normal left ventricular ejection fraction and no valvular disease. Angiography revealed general arteriosclerosis with significant
stenoses at the proximal left anterior descending, first
diagonal, proximal circumflex, and medial right coronary
arteries. Because we lacked suitable autologous graft
material owing to a positive Allen test and prior bilateral
saphenectomy (due to varicosis), we decided to use a
seeded NR-SIMA, for complete revascularization.
After institutional review board approval and informed
consent were obtained, an 8-cm skin vein from the right
forearm was taken in March 2004. Endothelial cells were
harvested and cultured as previously described [3]. The
NR-SIMA was selected because previous studies had
shown that this graft provided a higher density of endothelial cells after seeding compared with expanded polytetrafluoroethylene (ePTFE) grafts [2].
In April 2004, the patient underwent grafting using the
left internal mammary artery to the left descending
artery (including endarterectomy), the right vena saphena parva as a sequential bypass for the first diagonal
and circumflex artery, and the seeded NR-SIMA to bypass the right coronary artery. The internal diameters
were left descending artery, 1.0 mm; first diagonal artery,
1.5 mm; circumflex artery, 1.5 mm; and right coronary
artery, 2.5 mm. A no-touch technique was used during
implantation to avoid endothelial cell loss resulting from
manipulation.
During the postoperative period, the patient experienced arterial bleeding of a duodenal ulceration, which
needed to be treated interventionally. The patient was
sent home on postoperative day 19 in good health.
During follow-up, the patient did not have any adverse
events or restrictions. Patency of the grafts was evaluated
by a noninvasive multislice computed tomography scan
at discharge and at 20 months’ postoperatively. All grafts
were patent at both intervals (Fig 1).
Comment
Alternative grafts for performing complete revascularization, when no or insufficient autologous graft material is
available, needs to be investigated. Scott and colleagues
[4] showed the long-term impact of complete coronary
revascularization. At 20 years after surgery, the survival
rate for incomplete revascularization was 53%, but survival for those who had undergone complete revascularization was 70%. The most common reasons for incomplete
revascularization were the presence of small diameter ves0003-4975/07/$32.00
doi:10.1016/j.athoracsur.2006.08.003
Fig 1. Multislice computed tomography after 20 months of implantation shows a patent mammary artery at the left anterior descending
coronary artery, vena saphena parva sequential at the first diagonal,
and circumflex artery and the Shellhigh No-React bovine internal
mammary artery (NR-SIMA) at the right coronary artery.
sels and severe calcification, followed by nonavailability of
a suitable autologous conduit.
These data were supported by Osswald and colleagues
[5], who showed similar results. In their study, 180-day
mortality was significantly higher (24%; p ⫽ 0.005) in
patients with incomplete revascularization compared
with those who underwent complete revascularization
(15%). Alternative grafts are therefore needed for those
situations in which autologous material is not available or
the quality of such graft material does not permit its use.
An ideal artificial graft for coronary bypass surgery
should have a small diameter, be easy to implant, and
have “off-the-shelf” availability. Craig and colleagues [1]
presented a study of 7 patients who underwent implantation of a bovine internal mammary artery treated by
dialdehyde and sterilized with ethanol and propylene
oxide (Bioflow, Biovascular Inc, St Paul, MN). All 11
examined grafts were occluded at a mean follow-up of 19
months after implantation, despite the target vessels
being at least 1.5 mm in diameter. Among the remaining
patients, each of whom refused to be reevaluated, 42.8%
experienced recurrent angina pectoris.
Mitchell and colleagues [6] reported an angiographic
study of the Bioflow, with a patency rate of 15.8% at a
mean follow-up of 9.5 months (range, 3 to 23 months).
The dialdehyde tanning procedure removes the dendritic
cells and renders immunogenicity, but inevitably, the
lack of endothelial cells means that collagen is exposed to
blood circulation, creating a thrombogenic surface [6].
The No-React treatment is a heparin-based detoxification process that further stabilizes tissue cross-linking
and prevents the release of aldehydes [7]. No-React
CASE REPORT
DOHMEN ET AL
ENDOTHELIAL CELL-SEEDED BOVINE IMA
1169
treated tissue has been shown to inhibit calcification and
inflammatory reactions and resist infection while preserving cellular and connective tissue structures, which
denotes its biocompatibility [8]. A previous in vitro study
performed at our institute confirms this statement, that
No-React treated bovine internal mammary arteries can
be seeded with endothelial cells. We were, furthermore,
able to show that the endothelial cell density of the
seeded NR-SIMA graft was significantly higher than
ePTFE grafts. Encouraged by these results and an in vivo
study, we implanted the seeded NR-SIMA in a patient
with insufficient autologous graft availability to perform
complete revascularization. After 20 months of follow-up,
the mammary artery and the vena saphena parva were
both patent. Furthermore, the NR-SIMA was also patent,
and the patient was in New York Heart Association
functional class I, without any restrictions.
This excellent clinical result notwithstanding, this new
technique has some restrictions. For the moment, this
treatment is only available for patients with stable angina
pectoris, because the waiting time for a seeded NR-SIMA
graft is 4 to 6 weeks. A cell-culturing modification we
have performed has lead to a reduction of this waiting
time by 2 weeks. Nevertheless, new cell sources need to
be evaluated, such as progenitor cells, which have more
growth potential. This is under investigation and should,
in the future, allow time to treat patients with unstable
angina pectoris.
In conclusion, this alternative can be safely used in
patients with stable angina pectoris in which elective
bypass surgery can be performed.
References
1. Craig SR, Walker WS. The use of bovine internal mammary
artery (Bioflow) grafts in coronary artery surgery. Eur J Cardiothorac Surg 1994;8:43–5.
2. Dohmen PM, Posner S, Erdbruegger W, Konertz W. Human
endothelial cell seeding with the No-React treated internal
mammary arteries: perspective for the planned study and
outlook for the future. Cardiovasc Sci Forum 2006;3:8 –12.
3. Laube HR, Duwe J, Rutsch W, Konertz W. Clinical experience
with autologous endothelial cell-seeded polytetrafluoroethylene coronary artery bypass grafts. J Thorac Cardiovasc Surg
2000;120:134 – 41.
4. Scott R, Blackstone E, McCarthy PM, et al. Isolated bypass
grafting of the left internal thoracic artery to the left anterior
descending coronary artery: late consequences of incomplete
revascularization. J Thorac Cardiovasc Surg 2000;120:173– 84.
5. Osswald BR, Blackstone EH, Tochtermann U, et al. Does the
completeness of revascularization affect early survival after
coronary artery bypass grafting in elderly patients? Eur J Cardiothorac Surg 2001;20:120 – 6.
6. Mitchell IM, Essop AR, Scott JP, et al. Bovine internal mammary artery as a conduit for coronary revascularization: longterm results. Ann Thorac Surg 1993;55:120 –2.
7. Abolhoda A, Yu S, Oyarzun JR, McCormick JR, Bogden JD,
Gabbay S. Calcification of bovine pericardium: glutaraldehyde versus No-React biomodification. Ann Thorac Surg
1996;62:169 –74.
8. Reddy SL, Pillia J, Mitchell L, et al. First report of no-react
bovine internal mammary artery performance and patency.
Heart Surg Forum 2004;7:E446 –9.
FEATURE ARTICLES
Ann Thorac Surg
2007;83:1168 –9