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CARDIOVASCULAR
ENGINEERING Journal for Extracorporeal
Circulation, Assist Devices,Transplantation and
Artificial Organs
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Volume 8, 2003, No 1-2
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Computerized Image Analysis in the Quantitative
Assessment of Interstitial Fibrosis Late after Correction of Tetralogy of Fallot
T. H. F. Peters, H. S. Sharma, A. J. J. C. Bogers
Objective. To explore the possibilities of
computerized image analysis in determining the extent of right ventricular (RV)
fibrosis in tetralogy of Fallot (TF) by evaluating the expression pattern of
collagen and fibronectin in myocardial biopsies.
Methods: RV biopsies were obtained from 12 patients at corrective surgery
(TF1, age 0.8± 0.1 years) and 10 patients at reoperation for pulmonary
regurgitation after correction of TF (TF2, age 30.1± 2.4 years). Comparison was
made with 10 age matched patients operated for pulmonary autograft root
replacement (PAG) (age 27.4± 0.9 years) and 5 normal hearts (NL) from heart
valve donors (age 29.8± 3.9 years). Expression patterns of collagen and
fibronectin were analysed using the Leica Qwin Y2.2b standard image analysis
software.
Results: Total collagen expression was significantly higher in TF2 than
in TF1 (TF1 12.5± 0.7% vs. TF2 19.2± 2.4%, p<0.05), but not different from
NL, while PAG showed higher levels than NL (TF2 19.2± 2.4% vs. PAG 22.5± 2.7%
vs. NL 16.9± 1.7%, p<0.05). Interstitial collagen was also higher in TF2
(TF1 11.2± 0.7% vs. TF2 18.6± 2.3%, p<0.05). TF2 and PAG did not differ,
but PAG differed from NL (TF2 18.6± 2.3% vs. PAG 21.8± 2.7% vs. NL 16.1±
1.5%, p<0.05). Perivascular collagen, corrected for vascular lumen area, was
higher in TF1 (TF1 ratio 17.8± 1.9 vs. TF2 ratio 9.8± 1.2, p<0.05) but also
increased in PAG (TF2 ratio 9.8± 1.2 vs. PAG ratio 14.6± 2.2 vs. NL ratio
8.9± 1.6, p<0.05).
Total fibronectin expression showed no difference in TF1 and TF2, but lower
values of TF2 comparing with PAG and NL (TF2 14.7± 1.5% vs. PAG 20.2± 3.6% vs.
NL 20.3± 1.5%, p<0.05). There were lower values of interstitial fibronectin
in TF2 comparing with PAG and NL (TF2 14.1± 1.4% vs. PAG 19.8± 3.6% vs. NL
20.0± 1.5%, p<0.05). Perivascular fibronectin, corrected for vascular lumen
area, in TF2 was higher than in PAG and NL (TF2 ratio 7.1± 1.2 vs. PAG ratio
4.9± 0.9 vs. NL ratio 3.7± 0.5, p<0.05).
Conclusion: Computerized image analysis is a useful and effective adjunct
in the analysis of RV hypertrophy in TF. Using this technique we found a higher
content of total and interstitial collagen contents, but a lower perivascular
collagen ratio in older patients who got redo surgery. This was accompanied by a
lower amount of total and interstitial fibronectin and an increased fibronectin
perivascular ratio. Using this technique we also found that RV biopsies from
pulmonary autograft patients can not be regarded as normal, despite clinically
normal RV function. Our findings leave room for improvement of contemporary
clinical treatment of patients with TF by allowing an assessment of the adequacy
of timing for surgery.
(CVE. 2003; 8 (1/2): 114-120)
Key words: computerized image analysis, tetralogy of Fallot,
right ventricular hypertrophy, collagen, fibronectin
Ad J. J. C. Bogers, M.D., Ph.D.
Department of Cardiothoracic Surgery
Thoraxcenter Bd 156
Erasmus University Medical Center
P.O. Box 2040
NL-3000 CA Rotterdam
The Netherlands
E-mail: klomp@thch.azr.nl
      

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