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Heterotopic Cervical Heart Transplantation in Mice
Published on: August 25, 2015
Fibrosis in the transplanted heart and its relation to donor ischemic time. Assessment with polarized light
1Department of Medicine, University of Western Ontario, London, Canada.
Insights
Long ischemic times in heart transplantation increase cardiac allograft fibrosis. This myocardial fibrosis, identified soon after transplant, correlates with total ischemic duration, impacting diastolic function.
Area of Science:
- Cardiology
- Transplantation Immunology
- Pathology
Background:
- Long-distance organ procurement for cardiac allografts is common but linked to impaired diastolic function.
- Understanding the impact of ischemia on cardiac allografts is crucial for improving patient outcomes.
Purpose of the Study:
- To quantitatively evaluate the effect of total ischemic duration on myocardial fibrosis in cardiac transplant recipients.
- To assess the relationship between ischemia time and collagen content in transplanted hearts.
Main Methods:
- Analysis of 115 endomyocardial biopsy specimens from 36 cardiac transplant recipients.
- Quantification of interstitial collagen using polarization microscopy and digital image analysis.
- Correlation of fibrosis with total ischemic time, donor age, and hemodynamic parameters.
Main Results:
- Cardiac allograft fibrosis was significantly greater than in normal hearts (4.7% vs. 2.9%).
- The degree of fibrosis showed a strong correlation with total ischemic time (r = 0.60, p < 0.001).
- Myocyte damage was observed in 8 out of 36 patients.
Conclusions:
- Cardiac allograft fibrosis can be detected early after transplantation.
- Total ischemic duration is a significant determinant of post-transplant cardiac fibrosis.
- Ischemia-induced fibrosis may contribute to impaired diastolic function in heart allografts.
Abstract:
Long-distance procurement of cardiac allografts is commonly used to increase the supply of donor organs but has recently been associated with the development of impaired diastolic function. Therefore, the effect of the total ischemic duration on myocardial fibrosis was quantitatively evaluated in 36 cardiac transplant recipients in whom the ischemic time ranged from 70 to 363 (mean, 189 +/- 83) minutes. Interstitial collagen was quantified with polarization microscopy and digital image analysis in 115 endomyocardial biopsy specimens taken 5-10 days after surgery. The technique, developed for this study, showed excellent correlation with hydroxyproline analysis (r = 0.98, p less than 0.001). Collagen volume fraction in biopsy specimens from the transplanted hearts was significantly greater than that in biopsy samples from seven normal, age-matched autopsy hearts (4.7 +/- 1.9% vs. 2.9 +/- 0.6%, p less than 0.02). The degree of fibrosis correlated with the total ischemic time (r = 0.60, p less than 0.001). Donor age ranged from 10 to 51 years and did not correlate with the degree of fibrosis. No relation was found between the corresponding collagen content and right atrial pressure, pulmonary artery wedge pressure, or cardiac output measured at the time of biopsy. Myocyte damage was observed in eight of the 36 patients and was characterized by a striking loss of muscle birefringence. We conclude that cardiac allograft fibrosis may be identified shortly after transplantation and is dependent on the total ischemic duration.

