Mg. Buckley et al., Cardiac peptide stability, aprotinin and room temperature: importance for assessing cardiac function in clinical practice, CLIN SCI, 97(6), 1999, pp. 689-695
Brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and N-ter
minal ANP are good research indices of the severity of heart failure. The s
tability of these peptides at room temperature has become an important fact
or in assessing their use as indicators of cardiac function in routine clin
ical practice. Inhibitors such as aprotinin are routinely added in the bloo
d collection process, but may provide no benefit in sample collection and r
outine clinical practice. We assessed the stability of BNP, ANP and N-termi
nal ANP in blood samples collected in either the presence or the absence of
the protease inhibitor aprotinin. Blood, either with or without aprotinin,
was processed immediately (initial; 0 h) and after blood samples had been
left for 3 h, 2 days or 3 days at room temperature. These times were chosen
to reflect processing in a hospital outpatient clinic (2-3 h), or when pos
ted from general practice (2-3 days). Initial plasma BNP, ANP and N-termina
l ANP levels in the absence of aprotinin were 28.2+/-5.4, 44.2+/-7.9 and 19
97+/-608 pg/ml respectively, and were not significantly different from init
ial values in the presence of aprotinin (29.0+/-5.9, 45.2+/-8.0 and 2009+/-
579 pg/ml respectively). After 3 h at room temperature, there was a signifi
cant fall in ANP in the absence of aprotinin (36.7+/-7.9 pg/ml; P < 0.005),
but not in the presence of aprotinin (41.2+/-7.6 pg/ml). Both BNP and N-te
rminal ANP were unchanged in either the absence (BNP, 27.6+/-5.5 pg/ml; N-t
erminal ANP, 2099+/-613 pg/ml) or the presence (BNP, 29.4+/-5.6 pg/ml; N-te
rminal ANP, 1988+/-600 pg/ml) of aprotinin. After 2 days at room temperatur
e, ANP had fallen significantly in both the absence (16.9+/-3.4 pg/ml) and
the presence (24.0+/-5.0 pg/ml) of aprotinin compared with initial values,
and there was a significant difference in ANP levels in the absence and pre
sence of aprotinin (P < 0.001). ANP levels had decreased further after 3 da
ys at room temperature, to 11.9+/-3.4 pg/ml (no aprotinin) and 20.3+/-5.0 p
g/ml (aprotinin added); these values were significantly different (P = 0.00
2). In contrast, there was no change in the levels of BNP or N-terminal ANP
after 2 or 3 days at room temperature, in either the absence or the presen
ce of aprotinin. These studies indicate that aprotinin adds little benefit
to the stability of cardiac peptides at room temperature. Blood samples for
BNP and N-terminal ANP measurement used as a test of heart function in hos
pital clinics and by general practitioners in the community could be taken
into blood tubes containing only EDTA as anticoagulant and without the addi
tional step of adding the routinely used inhibitor aprotinin.