ELECTRIC MYOCARDIAL IMPEDANCE REGISTRATION IN HUMORAL REJECTION AFTERHEART-TRANSPLANTATION

Background: Because of the absent lymphocyte infiltrate, humoral-media ted rejection after heart transplantation is not diagnosed by the usua l staining technique (hematoxylin-eosin method) of the endomyocardial biopsy specimen. However, humoral rejection is characterized by a dist inct myocardial edema caused by capillary leakage. Because tissue edem a increases the electric myocardial impedance of the corresponding tis sue compartment the electric myocardial impedance method should be abl e to detect these episodes more reliably than biopsy. Methods: To eval uate this hypothesis eight DLA-matched beagle dogs were subjected to h eterotopic neck heart transplantation after multiple sensitization by skin grafts of the heart donor. For electric myocardial impedance regi strations rectangular impulses (wide 1 msec) were applied over two int ramyocardial electrodes and the impulse response was registered. Day-t o-day comparisons were made and an increase of electric myocardial imp edance of 10% or more was used as an indicator of rejection. To assess the influence of edema caused by electrode implantation, cortisone ad ministration, narcosis, ischemia, or reperfusion on the electric myoca rdial impedance, identical electrodes were implanted in the native hea rts of five additional dogs via lateral thoracotomy. These animals eac h received 100 mg methylprednisolone between postoperative days 20 and 22 and underwent heterotopic neck heart transplantation on postoperat ive day 28 without previous sensitization (protocol 2). Electric myoca rdial impedance electrodes were also implanted in these allografts (pr otocol 3). After transplantation myocardial biopsies were done every 2 days and the samples graded according to the International Society fo r Heart and Lung Transplantation classification in all dogs. Results: Despite triple-drug immunosuppression (cyclosporine A, prednisolone, a zathioprine) humoral rejection developed in all sensitized dogs as est ablished by immunofluorescent staining of myocardial biopsy samples an d functional deterioration. All episodes were diagnosed by electric my ocardial impedance (sensitivity 100%), whereas only in one case the bi opsy specimen was positive (International Society for Heart and Lung T ransplantation grade >1) (sensitivity 12.5%). All eight episodes could be treated successfully, that is, myocardial performance and electric myocardial impedance showed an immediate and full recovery. During th e first 12 days none of the nonsensitized dogs exhibited rejection. Pr otocol 2 indicated that narcosis and the administration of cortisone d id not per se have an influence on electric myocardial impedance and t he influence of electrode implantation was negligible. Contrarily, ede ma caused by ischemia and reperfusion during transplantation (protocol s 1 and 3) led to a significant increase in electric myocardial impeda nce. However, after 2 days this edema had faded away such that it no l onger disturbed rejection diagnosis. Conclusion: We conclude that the registration of the electric myocardial impedance diagnoses humoral re jection episodes after heart transplantation not only reliably but als o early, that is, before the onset of irreversible graft damage.