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Published in: Intensive Care Medicine 10/2003

01-10-2003 | Original

Plasma atrial natriuretic peptide and brain natriuretic peptide are increased in septic shock: impact of interleukin-6 and sepsis-associated left ventricular dysfunction

Authors: Rochus Witthaut, Christian Busch, Peter Fraunberger, Autar Walli, Dietrich Seidel, Günter Pilz, Ralph Stuttmann, Norbert Speichermann, Ljifane Verner, Karl Werdan

Published in: Intensive Care Medicine | Issue 10/2003

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Abstract

Objective

Interest has recently focused on the use of neurohormonal markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) as indices of left ventricular systolic dysfunction and prognosis in heart failure. Also, peptides belonging to the interleukin-6 (IL-6) family have been shown to induce ANP and BNP secretion. We hypothesized that BNP and ANP spillover in the peripheral circulation reflects left ventricular dysfunction and IL-6 production in septic shock.

Design and setting

Retrospective, clinical study in the medical intensive care unit of a university hospital.

Patients and participants

17 patients with septic shock and 19 control subjects.

Interventions

Collection of clinical and demographic data in relation to ANP, BNP, IL-6, and soluble TNF receptors (sTNF-R-p55, sTNF-R-p75) in plasma over a period of 4 days.

Measurements and results

In septic shock we found a significant increase in ANP (82.7±9.9 vs. 14.9±1.2 pg/ml) and BNP (12.4±3.6 vs. 5.5±0.7 pg/ml). Plasma ANP peaked together with IL-6. Peaks of ANP and IL-6 were significantly correlated (r=0.73; p<0.01). BNP was inversely correlated to cardiac index (r=–0.56; p<0.05).

Conclusions

ANP and BNP increase significantly in patients with septic shock. BNP reflects left ventricular dysfunction. ANP is related to IL-6 production rather than to cardiovascular dysfunction.
Literature
1.
go back to reference Nakao K, Ogawa Y, Suga S, Imura H (1992) Molecular biology and biochemistry of the natriuretic system. I. Natriuretic peptides. J Hypertens 10:907–912PubMed Nakao K, Ogawa Y, Suga S, Imura H (1992) Molecular biology and biochemistry of the natriuretic system. I. Natriuretic peptides. J Hypertens 10:907–912PubMed
2.
go back to reference Bold AJ de (1985) Atrial natriuretic factor: a hormone produced by the heart. Science 230:767–770PubMed Bold AJ de (1985) Atrial natriuretic factor: a hormone produced by the heart. Science 230:767–770PubMed
3.
go back to reference Sudoh T, Kangawa K, Minamino N, Matsuo H (1988) A new natriuretic peptide in porcine brain. Nature 332:78–81CrossRefPubMed Sudoh T, Kangawa K, Minamino N, Matsuo H (1988) A new natriuretic peptide in porcine brain. Nature 332:78–81CrossRefPubMed
4.
go back to reference Yasue H, Yoshimura M, Sumida H, Kikuta K, Kugiyama K, Jougasaki M, Ogawa H, Okumura K, Mukoyama M, Nakao K (1994) Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 90:195–203PubMed Yasue H, Yoshimura M, Sumida H, Kikuta K, Kugiyama K, Jougasaki M, Ogawa H, Okumura K, Mukoyama M, Nakao K (1994) Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 90:195–203PubMed
5.
go back to reference Mukoyama M, Nakao K, Saito Y, Ogawa Y, Hosoda K, Suga S, Shirakami G, Jougasaki M, Imura H (1990) Increased human brain natriuretic peptide in congestive heart failure. N Engl J Med 313:757–758 Mukoyama M, Nakao K, Saito Y, Ogawa Y, Hosoda K, Suga S, Shirakami G, Jougasaki M, Imura H (1990) Increased human brain natriuretic peptide in congestive heart failure. N Engl J Med 313:757–758
6.
go back to reference Gottlieb S, Kukin ML, Ahern D, Packer M (1989) Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure. J Am Coll Cardiol 13:153–159PubMed Gottlieb S, Kukin ML, Ahern D, Packer M (1989) Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure. J Am Coll Cardiol 13:153–159PubMed
7.
go back to reference Arakawa N, Nakamura M, Aoki H, Hiramori K (1996) Plasma brain natriuretic peptide concentrations predict survival after acute myocardial infarction. J Am Coll Cardiol 27:1656–1661CrossRefPubMed Arakawa N, Nakamura M, Aoki H, Hiramori K (1996) Plasma brain natriuretic peptide concentrations predict survival after acute myocardial infarction. J Am Coll Cardiol 27:1656–1661CrossRefPubMed
8.
go back to reference Hall C, Rouleau JL, Moye L, de Champlain J, Bichet D, Klein M, Sussex B, Packer M, Rouleau J, Arnold MO, Lamas GA, Sestier F, Gottlieb S, Wun CC, Pfeffer MA (1994) N terminal proatrial natriuretic factor. An independent predictor of long term prognosis after myocardial infarction. Circulation 89:1934–1942PubMed Hall C, Rouleau JL, Moye L, de Champlain J, Bichet D, Klein M, Sussex B, Packer M, Rouleau J, Arnold MO, Lamas GA, Sestier F, Gottlieb S, Wun CC, Pfeffer MA (1994) N terminal proatrial natriuretic factor. An independent predictor of long term prognosis after myocardial infarction. Circulation 89:1934–1942PubMed
9.
go back to reference Thaik CM, Calderone A, Takahashi N, Colucci WS (1995) Interleukin-1β modulates the growth and phenotype of neonatal rat cardiac myocytes. J Clin Invest 96:1093–1099PubMed Thaik CM, Calderone A, Takahashi N, Colucci WS (1995) Interleukin-1β modulates the growth and phenotype of neonatal rat cardiac myocytes. J Clin Invest 96:1093–1099PubMed
10.
go back to reference He Q, LaPointe MC (1999) Interleukin-1β regulation of the human brain natriuretic peptide promotor involves Ras-, Rac-, and p38 kinase-dependent pathways in cardiac myocytes. Hypertension 33:283–289PubMed He Q, LaPointe MC (1999) Interleukin-1β regulation of the human brain natriuretic peptide promotor involves Ras-, Rac-, and p38 kinase-dependent pathways in cardiac myocytes. Hypertension 33:283–289PubMed
11.
go back to reference Kuwahara K, Saito Y, Harada M, Ishikawa M, Ogawa E, Miyamoto Y, Hamanaka I, Kamitani S, Kajiyama N, Takahashi N, Nakagawa O, Masuda I, Nakao K (1999) Involvement of cardiotrophin-1 in cardiac myocyte-nonmyocyte interactions during hypertrophy of rat cardiac myocytes in vitro. Circulation 100:1116–1124PubMed Kuwahara K, Saito Y, Harada M, Ishikawa M, Ogawa E, Miyamoto Y, Hamanaka I, Kamitani S, Kajiyama N, Takahashi N, Nakagawa O, Masuda I, Nakao K (1999) Involvement of cardiotrophin-1 in cardiac myocyte-nonmyocyte interactions during hypertrophy of rat cardiac myocytes in vitro. Circulation 100:1116–1124PubMed
12.
go back to reference MacGowan GA, Mann DL, Kormos RL, Feldman AM, Murali S (1997) Circulating interleukin-6 in severe heart failure. Am J Cardiol 79:1128–1131CrossRefPubMed MacGowan GA, Mann DL, Kormos RL, Feldman AM, Murali S (1997) Circulating interleukin-6 in severe heart failure. Am J Cardiol 79:1128–1131CrossRefPubMed
13.
go back to reference Talwar S, Downie PF, Squire IB (1999) An immunolumino-metric assay for cardiotrophin-1: a newly identified cytokine is present in normal human plasma and is increased in heart failure. Biochem Biophys Res Commun 261:567–571CrossRefPubMed Talwar S, Downie PF, Squire IB (1999) An immunolumino-metric assay for cardiotrophin-1: a newly identified cytokine is present in normal human plasma and is increased in heart failure. Biochem Biophys Res Commun 261:567–571CrossRefPubMed
14.
go back to reference Tsutamoto T, Hisanga T, Wada A, Maeda K, Ohnishi M, Fukai D, Mabushi N, Sawaki M, Kinoshita M (1998) Interleukin-6 spillover in the peripheral circulation increase with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol 31:391–398PubMed Tsutamoto T, Hisanga T, Wada A, Maeda K, Ohnishi M, Fukai D, Mabushi N, Sawaki M, Kinoshita M (1998) Interleukin-6 spillover in the peripheral circulation increase with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol 31:391–398PubMed
15.
go back to reference Talwar S, Squire IB, Downie PF, Davies JE, Ng LL (2000) Plasma N terminal pro-brain natriuretic peptide and cardiotrophin 1 are raised in unstable angina. Heart 84:421–424CrossRefPubMed Talwar S, Squire IB, Downie PF, Davies JE, Ng LL (2000) Plasma N terminal pro-brain natriuretic peptide and cardiotrophin 1 are raised in unstable angina. Heart 84:421–424CrossRefPubMed
16.
go back to reference Torre-Amione G, Kapadia S, Benedct C, Oral H, Young JB, Mann DL (1996) Proinflammatory cytokine levels in patients with depressed left ventricular dysfunction. J Am Coll Cardiol 27:1201–1206PubMed Torre-Amione G, Kapadia S, Benedct C, Oral H, Young JB, Mann DL (1996) Proinflammatory cytokine levels in patients with depressed left ventricular dysfunction. J Am Coll Cardiol 27:1201–1206PubMed
17.
go back to reference Yokoyama T, Vaca L, Rossen RD, Durante W, Hazarika P, Mann DL (1993) Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart. J Clin Invest 92:2303–2312PubMed Yokoyama T, Vaca L, Rossen RD, Durante W, Hazarika P, Mann DL (1993) Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart. J Clin Invest 92:2303–2312PubMed
18.
go back to reference Werdan K (1998) The activated immune system in congestive heart failure-from dropsy to the cytokine paradigm. J Intern Med 243:87–92CrossRefPubMed Werdan K (1998) The activated immune system in congestive heart failure-from dropsy to the cytokine paradigm. J Intern Med 243:87–92CrossRefPubMed
19.
go back to reference Price S, Anning PB, Mitchell JA, Evans TW (1999) Myocardial dysfunction in sepsis: mechanisms and therapeutic implications. Eur Heart J 20:715–724CrossRefPubMed Price S, Anning PB, Mitchell JA, Evans TW (1999) Myocardial dysfunction in sepsis: mechanisms and therapeutic implications. Eur Heart J 20:715–724CrossRefPubMed
20.
go back to reference Müller-Werdan U, Werdan K (1999) Septic cardiomyopathy. Curr Opin Crit Care 5:415–421 Müller-Werdan U, Werdan K (1999) Septic cardiomyopathy. Curr Opin Crit Care 5:415–421
21.
go back to reference Parker MM, Shelhamer JH, Natanson C, Alling DW, Parillo JE (1989) Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis. Crit Care Med 15:923–929 Parker MM, Shelhamer JH, Natanson C, Alling DW, Parillo JE (1989) Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis. Crit Care Med 15:923–929
22.
go back to reference Pilz G, Fateh-Moghadam S, Viell B, Bujdoso O, Döring G, Marget W, Werdan K (1993) Supplemental immunoglobulin therapy in sepsis and septic shock-comparison of mortality under treatment with polyvalent i.v. immunoglobulin versus placebo: protocol of a multicenter, randomized, prospective, double-blind trial. Theor Surg 8:61–83 Pilz G, Fateh-Moghadam S, Viell B, Bujdoso O, Döring G, Marget W, Werdan K (1993) Supplemental immunoglobulin therapy in sepsis and septic shock-comparison of mortality under treatment with polyvalent i.v. immunoglobulin versus placebo: protocol of a multicenter, randomized, prospective, double-blind trial. Theor Surg 8:61–83
23.
go back to reference Werdan K, Pilz G, and the SBITS Study Group (1998). Polyvalent immune globulins. Shock [Suppl] 7:1918 Werdan K, Pilz G, and the SBITS Study Group (1998). Polyvalent immune globulins. Shock [Suppl] 7:1918
24.
go back to reference Bone R (1996) Sir Isaac Newton, sepsis, SIRS and CARS. Crit Care Med 24:1125–1128 Bone R (1996) Sir Isaac Newton, sepsis, SIRS and CARS. Crit Care Med 24:1125–1128
25.
go back to reference American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee (1992) Definitions for sepsis and multiple organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874PubMed American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee (1992) Definitions for sepsis and multiple organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874PubMed
26.
go back to reference Elebute EA, Stoner HB (1983) The grading of sepsis. Br J Surg 70:29–31 Elebute EA, Stoner HB (1983) The grading of sepsis. Br J Surg 70:29–31
27.
go back to reference Knaus WA, Draper EA, Wagner DP, Zimmermann JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMed Knaus WA, Draper EA, Wagner DP, Zimmermann JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMed
28.
go back to reference Gerbes AL, Witthaut R, Gülberg V, Thibault G, Bilzer M, Jüngst D (1992) Role of the liver in splanchnic extraction of atrial natriuretic factor in the rat. Hepatology 16:790–793PubMed Gerbes AL, Witthaut R, Gülberg V, Thibault G, Bilzer M, Jüngst D (1992) Role of the liver in splanchnic extraction of atrial natriuretic factor in the rat. Hepatology 16:790–793PubMed
29.
go back to reference Fraunberger P, Pfeiffer M, Cremer P, Holler E, Nagel D, Dehart I, Thein M, Walli AK, Seidel D (1992) Validation of an automated enzyme immunoassay for interleukin-6 for routine clinical use. Clin Chem Lab Med 36:797–801 Fraunberger P, Pfeiffer M, Cremer P, Holler E, Nagel D, Dehart I, Thein M, Walli AK, Seidel D (1992) Validation of an automated enzyme immunoassay for interleukin-6 for routine clinical use. Clin Chem Lab Med 36:797–801
30.
go back to reference Baim DS, Grossman W (1996) Cardiac catheterization, angiography, and intervention, 5th edn. Williams & Wilkins, Baltimore Baim DS, Grossman W (1996) Cardiac catheterization, angiography, and intervention, 5th edn. Williams & Wilkins, Baltimore
31.
go back to reference Muders F, Kromer EP, Griese DP, Pfeifer M, Hense HW, Riegger GAJ, Elsner D (1997) Evaluation of plasma natriuretic peptides as markers for left ventricular dysfunction. Am Heart J 134:442–449PubMed Muders F, Kromer EP, Griese DP, Pfeifer M, Hense HW, Riegger GAJ, Elsner D (1997) Evaluation of plasma natriuretic peptides as markers for left ventricular dysfunction. Am Heart J 134:442–449PubMed
32.
go back to reference Bakker J, Vincent JL (1993) Effects of norepinephrine and dobutamine on oxygen transport and consumption in a dog model of endotoxic shock. Crit Care Med 21:1248–1249PubMed Bakker J, Vincent JL (1993) Effects of norepinephrine and dobutamine on oxygen transport and consumption in a dog model of endotoxic shock. Crit Care Med 21:1248–1249PubMed
33.
go back to reference Pilz G, R Appel, P McGinn (1993) Calculation of the left ventricular stroke work index. Crit Care Med 21:1248–1249PubMed Pilz G, R Appel, P McGinn (1993) Calculation of the left ventricular stroke work index. Crit Care Med 21:1248–1249PubMed
34.
go back to reference Raine AEG, Erne P, Bürgisser E, Müller FB, Bolli P, Burkart F, Bühler FR (1986) Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med 315:533–537PubMed Raine AEG, Erne P, Bürgisser E, Müller FB, Bolli P, Burkart F, Bühler FR (1986) Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med 315:533–537PubMed
35.
go back to reference Hama N, Ito H, Shirakami G, Nakagawa O, Suga S, Ogawa Y, Masuda I (1995) Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation 92:1558–1564PubMed Hama N, Ito H, Shirakami G, Nakagawa O, Suga S, Ogawa Y, Masuda I (1995) Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation 92:1558–1564PubMed
36.
go back to reference Ogawa T, Linz W, Stevenson M, Bruneau BG, de Bold MLK, Chen JH, Eid H, Schölkens BA, de Bold AJ (1996) Evidence for load dependent and load independent determinants of cardiac natriuretic peptide production. Circulation 93:2059–2067PubMed Ogawa T, Linz W, Stevenson M, Bruneau BG, de Bold MLK, Chen JH, Eid H, Schölkens BA, de Bold AJ (1996) Evidence for load dependent and load independent determinants of cardiac natriuretic peptide production. Circulation 93:2059–2067PubMed
37.
go back to reference Edwards BS, Zimmermann RS, Schwab TR, Heublin DM, Burnett JC (1988) Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor. Circ Res 62:191–195PubMed Edwards BS, Zimmermann RS, Schwab TR, Heublin DM, Burnett JC (1988) Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor. Circ Res 62:191–195PubMed
38.
go back to reference Ognibene FP, Parker MM, Natanson C, Shelhamer JH, Parrillo JE (1988) Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock. Chest 93:903–910PubMed Ognibene FP, Parker MM, Natanson C, Shelhamer JH, Parrillo JE (1988) Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock. Chest 93:903–910PubMed
39.
go back to reference Pan J, Fukuda K, Saito M, Matsuzaki J, Kodama H, Sano M, Takahashi T, Kato T, and Ogawa S (1999) Mechanical stretch activates the JAK/STAT pathway in rat cardiomyocytes. Circ Res 84:1127–1136PubMed Pan J, Fukuda K, Saito M, Matsuzaki J, Kodama H, Sano M, Takahashi T, Kato T, and Ogawa S (1999) Mechanical stretch activates the JAK/STAT pathway in rat cardiomyocytes. Circ Res 84:1127–1136PubMed
40.
go back to reference Tsuruda T, Jougaschi M, Boerrigter G, Huntley BK, Chen HH, Dàssoro AB, Lu SC, Sarson AM, Cataliotti A, Burnett JC Jr (2002) Cardiotrophin-1 stimulation of cardiac fibroblast growth. Roles for glycoprotein 130/ leukemia inhibitory factor receptor and the endothelin type A receptor. Circ Res 90:128–134CrossRefPubMed Tsuruda T, Jougaschi M, Boerrigter G, Huntley BK, Chen HH, Dàssoro AB, Lu SC, Sarson AM, Cataliotti A, Burnett JC Jr (2002) Cardiotrophin-1 stimulation of cardiac fibroblast growth. Roles for glycoprotein 130/ leukemia inhibitory factor receptor and the endothelin type A receptor. Circ Res 90:128–134CrossRefPubMed
Metadata
Title
Plasma atrial natriuretic peptide and brain natriuretic peptide are increased in septic shock: impact of interleukin-6 and sepsis-associated left ventricular dysfunction
Authors
Rochus Witthaut
Christian Busch
Peter Fraunberger
Autar Walli
Dietrich Seidel
Günter Pilz
Ralph Stuttmann
Norbert Speichermann
Ljifane Verner
Karl Werdan
Publication date
01-10-2003
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 10/2003
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-003-1910-0

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