VENTRICULAR EXPRESSION OF BRAIN NATRIURETIC PEPTIDE GENE FOLLOWING ORTHOTOPIC CARDIAC TRANSPLANTATION IN CHILDREN - A 3 YEAR FOLLOW-UP

Objective: The aim was to examine ventricular brain natriuretic peptide (B-type natriuretic peptide, BNP) gene expression and to determine its relationship with ventricular BNP and circulating BNP levels in paediatric cardiac transplant recipients, over a three year period after transplantation. Methods: Total RNA extracted from endomyocardial right ventricular biopsy tissues (n = 26) of 13 cardiac transplant recipients (age range 5-17 years) and 10 normal hearts obtained at necropsy (age range 19-76 years) as controls was analysed by northern and slot blot hybridisations. Specific radioimmunoassay techniques were used to determine levels of BNP and atrial natriuretic peptide (A-type natriuretic peptide, ANP) in plasma (n = 26) and ventricular biopsy (n = 26) samples. Results: Ventricular BNP messenger ribonucleic acid (mRNA) levels from slot blot hybridisations in the transplanted heart [122(3) arbitrary units, range 97-143] were significantly higher (p < 0.01) than in the normal heart [63(5) arbitrary units, range 37-98]. Northern blot hybridisations confirmed this result and gave a major BNP mRNA transcript of approximately 900 nucleotides. There was no significant relationship between ventricular BNP mRNA levels and ventricular BNP (r = 0.15, p=0.5, n= 26) or plasma BNP levels (r=0.16, p = 0.4, n = 26). There was also no significant relationship between ventricular BNP mRNA levels and any of the haemodynamic variables, or immunosuppressive drugs. A ventricular ANP RNA transcript of approximately 900 nucleotides was detected in the transplanted heart but was below the limit of detection in the normal heart. For the long term study, increased levels of BNP and ANP in both plasma and ventricular samples were observed in the first year after transplantation, with a significant reduction (p < 0.01) in levels three years later. Conclusions: Ventricular BNP gene expression is increased at the mRNA level after heart transplantation in children. Expression of both ventricular BNP mRNA and ANP mRNA in the transplanted heart may be an important response in the modulation of cardiac function after transplantation.