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Updated: Oct 3, 2026
An Immunological Model for Heterotopic Heart and Cardiac Muscle Cell Transplantation in Rats
Published on: May 8, 2020
Capillary endothelia and cardiomyocytes differ in vulnerability to ischemia/reperfusion during clinical heart
A Koch1, T M Bingold, J Oberländer
1Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120, Heidelberg, Germany. achim_koch@ukl.uni-heidelberg.de
Insights
Capillary endothelial cell edema significantly worsens during heart transplantation, potentially leading to graft arteriosclerosis. Cardiomyocyte edema is less pronounced and resolves faster, suggesting endothelial injury is key to long-term graft health.
Area of Science:
- Cardiovascular Surgery
- Transplantation Immunology
- Cellular Biology
Background:
- Accelerated graft arteriosclerosis is a primary cause of late mortality following orthotopic heart transplantation.
- Peritransplant injury, particularly cardiomyocyte and capillary endothelial cell edema, influences graft outcomes.
Purpose of the Study:
- To investigate the extent and influence of peritransplant injury on cardiomyocytes and capillary endothelial cells during heart transplantation.
- To analyze the development of cell edema in cardiomyocytes and capillary endothelia at various stages of the transplantation procedure.
Main Methods:
- Morphometric ultrastructural analysis of myocardial biopsies from 29 donor hearts.
- Biopsies were collected at multiple time points: before cardioplegia, post-cardioplegia, pre-implantation, and at 30, 60 minutes, and 1 week after reperfusion.
- Quantitative electron microscopy assessed cardiomyocyte myofibril volume density and capillary endothelial barrier thickness.
Main Results:
- Cardiomyocyte myofibril volume density showed minor fluctuations and no significant changes across time points.
- Capillary endothelial barrier thickness significantly increased after cardioplegia (416±71 nm) and 30 minutes of reperfusion (473±45 nm) compared to baseline (353±21 nm).
- Endothelial edema remained significantly elevated at 60 minutes of reperfusion (453±50 nm) and returned to baseline levels after 1 week.
Conclusions:
- A significant capillary endothelial cell edema develops during heart transplantation, progressing more than cardiomyocyte edema.
- This endothelial edema persists into early reperfusion and may cause capillary perfusion inhomogeneities.
- Peritransplant endothelial injury is implicated as a contributing factor to the subsequent development of accelerated allograft arteriosclerosis.
Objective:
The development of accelerated graft arteriosclerosis is a major cause of late death after orthotopic heart transplantation. The influence and the extent of peritransplant injury, especially of cardiomyocyte or capillary endothelial cell edema is discussed.
Methods:
A morphometric ultrastructural analysis of myocardial biopsies from 29 donor hearts (21 male, age 34+/-11 years) was performed. Right ventricular biopsies were obtained before cardioplegia (A), immediately following cardioplegia (B) (Custodiol, Dr. F. Köhler Chemie GmbH, Alsbach-Hähnlein, Germany), before implantation (C), after 30 (D) or 60 (E) min of reperfusion and 1 week after transplantation (F). Mean ischemic time was 185+/-68 min. Quantitative electron microscopy was carried out in five samples per heart and time point and in 30 test fields per sample by 'random systematic sampling' and 'point and intersection counting'. As parameters for cell edema the volume density of myofibrils in cardiomyocytes and the mean barrier thickness of capillary endothelia were analyzed. P-values of less than 0.05 were regarded as significant. Significant differences in contrast to the previous values are marked by *.
Results:
The volume density of myofibrils (vol.%) was as follows: (B) 63.6+/-3.2, (C) 61.8+/-3.2, (D) 62.9+/-3.2, (E) 63.6+/-4.5. The mean barrier thickness (nm) was as follows: (A) 353+/-21, (B) 376+/-59, (C) 416+/-71*, (D) 473+/-45*; (E) 453+/-50*, (F) 379+/-39.
Conclusions:
Apart from a generally accepted edema of cardiomyocytes a relevant capillary endothelial cell edema develops during clinical heart transplantation. In contrast to cardiomyocytes the cell edema of endothelia shows a more pronounced and significant progression during cold ischemia and early reperfusion. After 60 min of reperfusion it is still significantly more pronounced than at the onset of ischemia. After 1 week there are no statistical differences compared to the initial values. Thus, an edema of capillary endothelia probably will trigger inhomogeneities in capillary perfusion. Peritransplant injury of endothelia may contribute to the later development of accelerated allograft arteriosclerosis.
