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J Thorac Cardiovasc Surg 1996;112:1128-1129
© 1996 Mosby, Inc.

LETTERS TO THE EDITOR

Atrial natriuretic peptide release after cardiac transplantation

Cardiothoracic Transplant Centre
Wythenshawe Hospital
Manchester, United Kingdom

To the Editor:

We read with interest the article "Atrial Natriuretic Peptide Release at Rest and With Exercise After Cardiac Transplantation With the Bicaval Technique" by Jahnke and associates (J Thorac Cardiovas Surg 1995;110:1600-5). We have been interested in the significance of the high levels of natriuretic peptides released after cardiac transplantation. Our findings, ¹ presented before the New York meeting of The International Society for Heart and Lung Transplantation in March 1996, correlate in some aspects with the findings of Jahnke and his associates.

High levels of plasma atrial natriuretic peptide (ANP) and ventricular expression of brain natriuretic peptide (BNP) have been identified after standard orthotopic cardiac transplantation. ^2-4 It was postulated that the large atrial mass after transplantation maintains the secretion of the high levels of ANP. ⁵ The significance of high levels of BNP after cardiac transplantation is unknown. ⁴ We have studied 40 ambulatory, randomly selected patients 6 months to 1 year after cardiac transplantation. Plasma levels of both ANP and BNP were elevated in patients who had bicaval orthotopic heart transplantation with small atrial mass (ANP, 197.9 ± 30.22 pg/ml; BNP, 7.4 ± 7.1 pg/ml [mean ± standard deviation]) and in patients who had standard orthotopic heart transplantation and large atrial mass (ANP, 191.3 ± 44.6.88 pg/ml; BNP, 10.9 ± 7.6 pg/ml) in comparison with normal healthy volunteers (ANP, 95.7 ± 30.1 pg/ml; BNP, 1.18 ± 0.18; p < 0.0001 and p < 0.0001, respectively). ANP levels were not significantly different between the bicaval and the standard group. These data suggest that high levels of ANP were synthesized and secreted by the transplanted denervated human heart, regardless of the transplantation technique. Despite the near complete denervation with the bicaval technique, ANP secretion continued, supporting the findings of Jahnke and colleagues. Lower mean systemic pressure and high serum urea content are associated with higher levels of ANP (p < 0.05), which can be the result of the vasodilator potential of ANP. BNP levels were significantly higher in the standard group (10.9 ± 7.6 pg/ml) than in the bicaval group (7.4 ± 7.1 pg/ml; p = 0.01). Patients in the standard group had a higher mean pulmonary artery pressure, right ventricular systolic pressure, and transpulmonary gradient. Linear regression analysis showed that faster heart rate, high mean pulmonary artery pressure, high pulmonary capillary wedge pressure, high transpulmonary gradient and higher cyclosporine trough levels are associated with higher levels of BNP (p < 0.05). We found higher levels of BNP in the standard group than in the bicaval group. The increased BNP was associated with an increase in the right ventricular afterload, manifested by a raised transpulmonary gradient and raised pulmonary capillary wedge pressure without overt ventricular failure. We have demonstrated a positive correlation between the BNP levels and heart rate, which we suppose is another marker for ventricular strain. Our findings correlate well with current understanding of BNP physiology. Plasma levels of BNP mainly reflect the degree of ventricular afterload. ⁶

There was no correlation between left ventricular systolic function (echo recorded ejection fraction) and BNP. We can assume that BNP levels after transplantation reflect predominantly right ventricular and left ventricular diastolic function. There was a positive correlation between the BNP and trough cyclosporine levels. Cyclosporine therapy tends to increase sympathetic activity, and this may contribute to posttransplantation pulmonary and systemic hypertension increasing the afterload. Another contributor is salt and water retention caused by stimulation of the renin-angiotensin-aldosterone system. It seems that the increased production of natriuretic peptides is a normal physiologic response to the hypertension and increased water and salt retention. Right atrial pressure, ejection fraction, serum creatinine, serum electrolytes, and the histologic grade of rejection did not show significant correlation with raised ANP and BNP after either technique of orthotopic heart transplantation. Unlike Jahnke and colleagues, we found no correlation between cold ischemic time and the release of natriuretic peptides.

In summary, there is no correlation between natriuretic peptide secretion and atrial mass or renal function. Differential regulation of ANP and BNP seems to influence the secretion of both hormones after transplantation. BNP correlates predominantly with right ventricular performance and afterload. The bicaval technique seems to be associated with better right ventricular performance. The ANP vasodilator effect may be a compensatory mechanism to the cyclosporine hypertensive effect. Measuring natriuretic peptide levels in other solid organ transplantation may identify the cause and effect relationship between cyclosporine therapy and hypertension-related diastolic dysfunction.

References

1. El Gamel A, Keevil B, Woodcock A, Campbell C, Deiraniya A, Yonan N. The significance of raised atrial and ventricular natriuretic peptides following cardiac transplantation. J Heart Lung Transplant 1996;15:S60.
   
2. Rubin DA, Uretsky BF, Zerbe TR, Estrada Quintero T, Murali S. Increased plasma atrial natriuretic peptide levels after heart transplant: relation to ventricular expression and severity of rejection. Am Heart J 1994;128:769-73.[Medline]
   
3. Ationu A, Sorensen K, Whitehead B, Singer D, Burch M, Carter ND. Ventricular expression of brain natriuretic peptide gene following orthotopic cardiac transplantation in children at three year follow up. Cardiovasc Res 1993;27:2135-9.[Abstract/Free Full Text]
   
4. Ationu A, Burch M, Singer D, Littleton P, Carter N. Cardiac transplantation affects ventricular expression of brain natriuretic peptide. Cardiovasc Res 1993;27:188-91.[Abstract/Free Full Text]
   
5. Singer D, Buckley G, Macgregor G, Khaghani A, Banner N, Yacoub M. Raised concenteration of plasma atrial natriuretic peptides in cardiac transplant recipients. BMJ 1986;293:1391-2.
   
6. Yoshimura M, Yasue H, Okumura K, Ogawa H, Jougasaki M, Mukoyama M, et al. The beneficial effect of atrial natriuretic peptide on cyclosporine nephrotoxicity. Am J Hypertens 1990;3:204-10.[Medline]
   

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This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Ahmed El Gamel Colin Campbell Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gamel, A. E. Articles by Deiraniya, A. Search for Related Content PubMed PubMed Citation Articles by Gamel, A. E. Articles by Deiraniya, A.