CARDIOVASCULAR
ENGINEERING
Journal for Extracorporeal Circulation, Assist Devices,Transplantation and Artificial Organs

Volume 8, 2003, No 1-2


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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