Adrenomedullin (ADM) is a vasoactive and natriuretic peptide. While it is known that ADM is increased in failing human ventricles, the expression of ADM in human ventricular allografts remains unknown. The present study was designed to investigate tissue localization and intensity of ADM expression in ventricular biopsy specimens and to characterize ventricular ADM in human cardiac allografts. Thirty-three post-transplant endomyocardial biopsy specimens were examined immunohistochemically. The average score (range: 0-4) of ADM immunoreactivity (IR) was 2.4±0.9 (mean±standard deviation). Right ventricular (RV) systolic pressure was significantly increased with high ADM-IR (p=0.048) and the ADM-IR positively associated with myocyte size (r2=0.23, p=0.010). In contrast, ADM-IR was not associated with systemic blood pressure, serum creatinine, cyclosporine concentration, cardiac fibrosis, or allograft rejection. The present study shows that ADM-IR is present in human ventricular endomyocardium after transplantation, and ADM-IR is associated with the magnitude of RV pressure and myocyte size, suggesting an important role for ventricular ADM in the counteraction against overload as well as in the progress of myocyte hypertrophy after heart transplantation.
Bibliographical noteFunding Information:
We thank Dr. Kenji Notohara, Division of Anatomic Pathology, Mayo Clinic Rochester, for helpful discussion. This work was supported by grants from the American Heart Association of the Minnesota Affiliate (MN-97-GB-06), the National Institutes of Health (HL36634 and HL07111), the Miami Heart Research Institute, the Bruce and Ruth Rappaport Program in Vascular Biology and the Mayo Foundation. The first author was supported by a fellowship of the Japan Heart Foundation. We gratefully thank Linda Combs for her assistance in preparing the manuscript.
- Heart transplantation