Full text of DOI:10.1007/BF03343878

J. Endocrinol. Invest. 24: RC22-RC24, 2001
RAPID COMMUNICATION
Pro-atrial natriuretic peptide hormone from right atria
is correlated with cardiac depression in septic patients
B. Mazul-Sunko*, N. Zarkovic**, N. Vrkic***, R. Klinger****, M. Peric*, M. Bekavac-Beslin*****,
M. Novkoski*, A. Krizmanic*, A. Gvozdenovic*, and E. Topic***
Departments of *Anesthesiology and Intensive Care Medicine, ***Clinical Chemistry and *****Surgery, University Hospital
“Sestre Milosrdnice”, and **Department of Molecular Medicine, Institute “Rudjer Boskovic”, Zagreb, Croatia;
****Biomedica Gruppe, Graz, Austria
ABSTRACT. N-terminal pro-atrial natriuretic peptide [proANP(1-98)] has been extensively investiga-
ted in patients with chronic heart failure and ishemic heart disease. It is found to be a better marker of
cardiac dysfunction than atrial natriuretic peptide (ANP). The possible involvement of proANP(1-98) in
cardiac depression caused by sepsis has not been studied yet. Therefore, we analyzed atrial plasma con-
centration of proANP(1-98) in 17 septic patients with hemodynamic variables measured or calculated
using pulmonary artery catheter. The results of altogether 96 measurements show a significant negative
correlation of proANP(1-98) and cardiac index (p<0.024), oxygen delivery (p<0.03) and oxygen con-
sumption (p<0.03). There is also a positive correlation with pulmonary vascular resistance (p<0.03).
ProANP(1-98) is significantly higher in patients who developed acute respiratory distress syndrome
(ARDS) (p<0.001). This study implies that proANP(1-98) is a possible novel hormone marker of cardiac
depression caused by sepsis that could be used for prediction of ARDS.
(J. Endocrinol. Invest. 24: RC22-RC24, 2001)
©2001, Editrice Kurtis
INTRODUCTION
this way is involved in fluid, electrolyte and blood pressure
homeostasis (5). Effects of ANP have been well investigated
in chronic heart failure (6), myocardial infarction (7) and acute
renal failure (8); it is a reliable marker of cardiac dysfunction
in congestive heart failure. proANP(1-98) is found to be even
a better prognostic marker in patients with ishemic heart dis-
ease and myocardial infarction than ANP (9).
The role of proANP(1-98) in hemodynamic changes caused
by severe sepsis is less extensively investigated, although
cardiac depression and disturbances in fluid hemostasis are
major problems in these patients. Therefore, we analyzed
the correlation between atrial plasma level of proANP(1-
98) and hemodynamic variables.
Atrial natriuretic peptide (ANP) is a peptide hormone synthe-
sized in atrial myocites as a prohormone and stored in secre-
tory granules as a 120 amino acid prohormone (1). The most
important stimulus for the release of hormones into circula-
tion is stretch of the myocyte fibers (2). On release the pro-
hormone is slit into equimolar amounts of the highly biologi-
cally active proANP (99-126), also known as α-ANP and the
N-terminal part proANP(1-98) (3). Alpha-ANP binds to spe-
cific receptors and therefore is rapidly cleared from circula-
tion with a half-life of 3-4 min. No receptors for proANP(1-98)
are known today, therefore this peptide circulates longer,
which leads to significant higher concentrations in blood com-
pared to α-ANP (4). Thus, circulating levels of proANP(1-98)
are less sensitive to pulsatile secretion of ANP and may bet-
ter reflect chronic levels of ANP secretion than the rapidly
fluctuating levels of α-ANP.
MATERIALS AND METHODS
Patients
ANP has vasorelaxing, natriuretic and diuretic effects and in
Seventeen critically ill septic patients were included in the
study. Sepsis was defined as a positive systemic inflamma-
tory response (SIRS) and a positive microbiological finding
or an ultrasound or X-ray examination consistent with in-
flammatory focus. An attending physician according to clin-
ical indication inserted pulmonary artery catheter. We used
Opti-Q or Oximetrix catheter (Abbot – Critical Care
System, Abbot Laboratories, North Chicago, IL, USA).
Blood samples for determining proANP(1-98) were taken
from the proximal part of pulmonary artery catheter that
Key-words: ProANP(1-98), plasma, intensive care, sepsis, cardiac depression, ARDS.
Correspondence: Dr. Branka Mazul-Sunko, Department of Anesthesiology
and Intensive Care, University Hospital “Sestre Milosrdnice”, Vinogradska 29,
HR-10 000 Zagreb, Croatia.
E-mail: brankas@phy.hr
Accepted May 31, 2001.
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B. Mazul-Sunko, N. Zarkovic, N. Vrkic, et al.
CI vs ANP (casewise MD deletion)
ANP=4533.7-277.5* CI
DO2 vs ANP (casewise MD deletion)
ANP=4545.6-2.064* DO
VO2 vs ANP (casewise MD deletion)
ANP=4118.6-4.856* VO
Correlation: r=-0.25242
Correlation: r=-0.22012
Correlation: r=-0.2153
A 8000
7000
6000
5000
4000
3000
2000
1000
0
B 8000
7000
6000
5000
4000
3000
2000
1000
0
C 8000
7000
6000
5000
4000
3000
2000
1000
0
Regression
Regression
95% confid.
Regression
95% confid.
95% confid.
0
1
2
3
4
5
6
7
8
-200
0
200 400 600 800 1000 1200
DO2
0
100 200 300 400 500 600 700
VO2
CI
Fig. 1 - Correlation between pro-atrial natriuretic peptide (proANP; fmol/ml) and: A) cardiac index (CI; l/m2); B) oxygen delivery (DO2
ml/min/m2); C) oxygen consumption (VO2; ml/min/m2).
is situated in right atria where ANP is predominantly re-
leased. At the same time, a blood sample for analysis of
oxygen parameters was taken. Hemodynamic measure-
ments were made immediately after drawing blood sam-
ples. Pressure variables were directly measured from pul-
monary artery catheter. Cardiac output was determined
by termodilution technique. All calculated variables are ex-
pressed as index values adapted to body surface area. The
Hospital Ethics Committee approved the study.
kit is a sandwich enzyme immunoassay designed to determine
proANP(1-98) directly in biological fluids – human serum or
plasma.
Statistics
Linear regression analysis was used to determine correla-
tion of proANP(1-98) and hemodynamic variables. Non-
parametric statistics – Kruskall – Wallis test was used to
analyze if patients with and without acute respiratory dis-
tress syndrome (ARDS) belong to the same distribution
concerning proANP(1-98).
Blood samples
Blood samples (3 ml) were taken from the proximal part of
the pulmonary artery catheter. It was collected into pre-
chilled glass tubes containing EDTA (1 ml/ml blood) and
aprotinin 75 KIU per tube). Blood was spun down and
serum stored deep-frozen.
RESULTS
There is a significant negative correlation between cardiac
index and proANP(1-98) (p<0.024) (Fig. 1A). Oxygen de-
livery is also negatively correlated with proANP(1-98) atri-
al concentration (p<0.03) (Fig. 1B). Oxygen consumption
is inversely correlated with proANP(1-98) (Fig. 1C).
Among resistance variables, there was statistically signifi-
Assays
proANP(1-98) Immunoassay Novel genuine proANP(1-98)
ELISA (Biomedica, Austria) was used. The proANP(1-98) test
Categorized histogram variable: ANP
A
25
20
15
10
5
25
20
15
10
5
B
Fig. 2 - Different distribution of pro-atri-
al natriuretic peptide (proANP) (1-98) val-
ues (fmol/ml) in two groups of patients:
patients without (A, ARDS 0) and with (B,
ARDS 1) acute respiratory distress syn-
drome (ARDS).
0
0
-1000
1000 3000 5000 7000 9000
2000 4000 6000 8000
ARDS: 0
-1000 1000 3000 5000 7000 9000
0
0
2000 4000 6000 8000
ARDS: 1
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ProANP in cardiac depression and sepsis
ACKNOWLEDGMENTS
cant correlation only with pulmonary vascular resistance.
We did not find a correlation between any pressure vari-
able and proANP(1-98).
This study was supported by the Croatian Ministry of Science and by
company Biomedica, Austria.
ProANP(1-98) is significantly higher in patients with ARDS.
Mean value in ARDS patients was 4165 1236 fmol/ml, while
in patients who did not have ARDS mean proANP(1-98)
value was 2388 1285 fmol/ml. Difference is significant at
p<0.001 (Fig. 2).
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