Capillary endothelia and cardiomyocytes differ in vulnerability to ischemia/reperfusion during clinical heart transplantation

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 (R), Dr. F. Kohler Chemie GmbH, Alsbach-Hahnlein, Germany), before implantation (C), after 30 (D) or 60 (E) min of reperfusion and I 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 I 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. (C) 2001 Elsevier Science B.V. All rights reserved.