Neuroendocrine profiling of humans receiving cardiac allografts.
BACKGROUND
Several studies have investigated changes in circulating hormones and markers of cardiac status after heart transplantation in humans. As a result, plasma levels of various hormones and autocoids have been associated with cardiac allograft rejection status. However, no clear associations can be defined given the highly contradictory nature of the available literature.


METHODS
In this study of 69 consecutive heart transplant patients followed for >2 years we examine the relationship between neurohumors potentially related to allograft rejection and endomyocardial biopsy grade of rejection (according to the ISHLT) and hemodynamic status. Markers assessed include brain natriuretic peptide (BNP), amino-terminal pro-BNP (N-BNP), atrial natriuretic factor (ANF), adrenomedullin, interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, troponin C and C-reactive protein.


RESULTS
The highest plasma levels for most neurohumors were found shortly after surgery and showed a trend towards normalization with time. BNP and N-BNP were the only significantly elevated plasma analytes for patients with Grade 3 rejection as compared with other ISHLT grades. ANF plasma levels correlated with BNP and N-BNP in Grades 0 to 2, but not in Grade 3, suggesting that in this rejection grade the usual coordinated changes observed in BNP and ANF secretion no longer exist. Cardiac filling pressures were correlated with plasma BNP, N-BNP and ANF levels only for Grades 0 and 1.


CONCLUSIONS
The timing of blood sampling after transplantation influences the level of the neurohumors measured, which may help explain the conflicting literature reports on the association between neurohumor levels and rejection grade. The significant increase in circulating levels of BNP and N-BNP observed in most cases of Grade 3 rejection occurred with no apparent relationship to post-transplantation time, which suggests a specific influence of acute rejection on BNP gene expression.
Ogawa
Tsuneo
T
Cardiovascular Endocrinology Laboratory, University of Ottawa Heart Institute, Ontario, Canada.
Veinot
John P
JP
Davies
Ross A
RA
Haddad
Haissam
H
Smith
Stuart J
SJ
Masters
Roy G
RG
Hendry
Paul J
PJ
Starling
Randall
R
de Bold
Mercedes Kuroski
MK
Ponce
Amalia
A
Ma
Kenneth K
KK
Williams
Kathryn
K
de Bold
Adolfo J
AJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D006328:Cardiac Catheterization; D015331:Cohort Studies; D004452:Echocardiography; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011182:Postoperative Care; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014184:Transplantation, Homologous; D019209:Troponin C / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000097:blood
D015415:Biomarkers; D007375:Interleukin-1; D015850:Interleukin-6; D019209:Troponin C; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D002097:C-Reactive Protein; D048051:p38 Mitogen-Activated Protein Kinases