Skip to main content
Erschienen in: Intensivmedizin und Notfallmedizin 6/2009

01.09.2009 | Leitthema

Neue Therapiekonzepte bei akut dekompensierter Herzinsuffizienz

verfasst von: Dr. S.A. Lehinant, V. Mitrovic

Erschienen in: Intensivmedizin und Notfallmedizin | Ausgabe 6/2009

Einloggen, um Zugang zu erhalten

Zusammenfassung

Bei der Behandlung der akut dekompensierten Herzinsuffizienz stehen seit Kurzem neue Therapiekonzepte bereit. Die Wirkweise der neuen Substanzen wird über Guanylatzyklase vermittelt. cGMP entsteht aus Guanosintriphosphat. Hierfür sind 2 Isoenzyme der Guanylatzyklase verantwortlich: Eine ist in die Plasmamembran eingelagert und wird durch natriuretische Peptide stimuliert. Die andere findet sich im Zytosol bestimmter Zellen. Es handelt sich um ein Häm-Protein, das durch Stickstoffmonoxid aktiviert wird. Nesiritide und Ularitide sind natriuretische Peptide, die an der plasmamembrangebundenen Guanylatzyklase wirken und vasodilatatorische, natriuretische und diuretische Effekte aufweisen. Cinaciguat aktiviert die Synthese von cGMP, indem es die zytosolische Guanylatzyklase in seinem NO-unempfindlichen, eisenoxydierten oder Häm-freien Zustand erkennt und bindet. Diese Substanz wirkt sehr gut unter oxidativem Stress. Vorläufige Studien mit Cinaciguat zeigen eine beachtliche Verbesserung der Hämodynamik und eine deutliche Symptomlinderung unter Aufrechterhaltung der Nierenfunktion.
Literatur
1.
Zurück zum Zitat Boerrigter G, Lapp H, Burnett JC (2009) Modulation of cGMP in heart failure: a new therapeutic paradigm. In: Schmidt HHHW et al (ed) cGMP: generators, effectors and therapeutic implications. Handbook of Experimental Pharmacology 191. Springer, Berlin Heidelberg, pp 485–507 Boerrigter G, Lapp H, Burnett JC (2009) Modulation of cGMP in heart failure: a new therapeutic paradigm. In: Schmidt HHHW et al (ed) cGMP: generators, effectors and therapeutic implications. Handbook of Experimental Pharmacology 191. Springer, Berlin Heidelberg, pp 485–507
2.
Zurück zum Zitat Boerrigter G, Costello-Boerrigter LC, Cataliotti A et al (2007) Targeting heme-oxidized soluble guanylate cyclase with BAY 58-2667 in experimental heart failure. BMC Pharmacol 7:P9CrossRef Boerrigter G, Costello-Boerrigter LC, Cataliotti A et al (2007) Targeting heme-oxidized soluble guanylate cyclase with BAY 58-2667 in experimental heart failure. BMC Pharmacol 7:P9CrossRef
3.
Zurück zum Zitat Dickstein K, Cohen-Solal A, Filippatos G et al (2008) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the TaskForce for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29:2388–2442PubMedCrossRef Dickstein K, Cohen-Solal A, Filippatos G et al (2008) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the TaskForce for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29:2388–2442PubMedCrossRef
4.
Zurück zum Zitat Evgenov OV, Pacher P, Schmidt PM et al (2006) NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov 5:755–768PubMedCrossRef Evgenov OV, Pacher P, Schmidt PM et al (2006) NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov 5:755–768PubMedCrossRef
5.
Zurück zum Zitat Feil R, Kemp-Harper B (2006) cGMP signalling: from bench to bedside. Conference on cGMP generators, effectors and therapeutic implications. EMBO Rep 7:149–153PubMedCrossRef Feil R, Kemp-Harper B (2006) cGMP signalling: from bench to bedside. Conference on cGMP generators, effectors and therapeutic implications. EMBO Rep 7:149–153PubMedCrossRef
6.
Zurück zum Zitat Frey R, Muck W, Unger S et al (2008) Pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase activator cinaciguat (BAY 58-2667) in healthy male volunteers. J Clin Pharmacol 48:1400–1410PubMedCrossRef Frey R, Muck W, Unger S et al (2008) Pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase activator cinaciguat (BAY 58-2667) in healthy male volunteers. J Clin Pharmacol 48:1400–1410PubMedCrossRef
7.
Zurück zum Zitat Lapp H, Mitrovic V, Franz N et al (2007) BAY 58-2667, a soluble guanylate cyclase activator, improves cardiopulmonary haemodynamics in acute decompensated heart failure and has a favourable safety profile. BMC Pharmacol 7:S9CrossRef Lapp H, Mitrovic V, Franz N et al (2007) BAY 58-2667, a soluble guanylate cyclase activator, improves cardiopulmonary haemodynamics in acute decompensated heart failure and has a favourable safety profile. BMC Pharmacol 7:S9CrossRef
8.
Zurück zum Zitat Liang KV, Williams AW, Greene EL, Redfield MM (2008) Acute decompensated heart failure and the cardiorenal syndrome. Crit Care Med 36:S75–S88PubMedCrossRef Liang KV, Williams AW, Greene EL, Redfield MM (2008) Acute decompensated heart failure and the cardiorenal syndrome. Crit Care Med 36:S75–S88PubMedCrossRef
9.
Zurück zum Zitat Luss H, Mitrovic V, Seferovic PM et al (2008) Renal effects of ularitide in patients with decompensated heart failure. Am Heart J 155:1012.e1–e8PubMedCrossRef Luss H, Mitrovic V, Seferovic PM et al (2008) Renal effects of ularitide in patients with decompensated heart failure. Am Heart J 155:1012.e1–e8PubMedCrossRef
10.
Zurück zum Zitat Mentzer RM Jr, Oz MC, Sladen RN et al (2007) Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery: the NAPA Trial. J Am Coll Cardiol 49:716–726PubMedCrossRef Mentzer RM Jr, Oz MC, Sladen RN et al (2007) Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery: the NAPA Trial. J Am Coll Cardiol 49:716–726PubMedCrossRef
11.
Zurück zum Zitat Meyer M, Richter R, Brunkhorst R et al (1996) Urodilatin is involved in sodium homeostasis and exerts sodium-state-dependent natriuretic and diuretic effects. Am J Physiol 271(3 Pt 2):F489–F497PubMed Meyer M, Richter R, Brunkhorst R et al (1996) Urodilatin is involved in sodium homeostasis and exerts sodium-state-dependent natriuretic and diuretic effects. Am J Physiol 271(3 Pt 2):F489–F497PubMed
12.
Zurück zum Zitat Mitrovic V, Lapp H, Franz N et al (2008) The soluble guanylate cyclase activator cinaciguat (BAY 58-2667) has a favourable safety profile and improves cardiopulmonary haemodynamics in acute decompensated heart failure. Poster presented at Heart Failure 14–17 June, Milan, Italy Mitrovic V, Lapp H, Franz N et al (2008) The soluble guanylate cyclase activator cinaciguat (BAY 58-2667) has a favourable safety profile and improves cardiopulmonary haemodynamics in acute decompensated heart failure. Poster presented at Heart Failure 14–17 June, Milan, Italy
13.
Zurück zum Zitat Mitrovic V, Seferovic PM, Simeunovic D et al (2006) Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J 27:2823–2832PubMedCrossRef Mitrovic V, Seferovic PM, Simeunovic D et al (2006) Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J 27:2823–2832PubMedCrossRef
14.
Zurück zum Zitat Mitrovic V, Luss H, Nitsche K et al (2005) Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. Am Heart J 150:1239PubMedCrossRef Mitrovic V, Luss H, Nitsche K et al (2005) Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. Am Heart J 150:1239PubMedCrossRef
15.
Zurück zum Zitat Publication Committee for the VMAC Investigators (2002) Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 287:1531–1540CrossRef Publication Committee for the VMAC Investigators (2002) Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 287:1531–1540CrossRef
16.
Zurück zum Zitat Sackner-Bernstein JD, Skopicki HA, Aaronson KD (2005) Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 111:1487–1491PubMedCrossRef Sackner-Bernstein JD, Skopicki HA, Aaronson KD (2005) Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 111:1487–1491PubMedCrossRef
17.
Zurück zum Zitat Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K (2005) Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA 293:1900–1905PubMedCrossRef Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K (2005) Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA 293:1900–1905PubMedCrossRef
18.
Zurück zum Zitat Schmidt HHHW, Schmidt PM, Stasch JP (2009) NO- and haem-independent soluble guanylate cyclase activators. Handb Exp Pharmacol 191:313–341 Schmidt HHHW, Schmidt PM, Stasch JP (2009) NO- and haem-independent soluble guanylate cyclase activators. Handb Exp Pharmacol 191:313–341
19.
Zurück zum Zitat Schmidt PM, Schramm M, Schroder H et al (2004) Identification of residues crucially involved in the binding of the heme moiety of soluble guanylate cyclase. J Biol Chem 279:3025–3032PubMedCrossRef Schmidt PM, Schramm M, Schroder H et al (2004) Identification of residues crucially involved in the binding of the heme moiety of soluble guanylate cyclase. J Biol Chem 279:3025–3032PubMedCrossRef
20.
Zurück zum Zitat Schmidt P, Schramm M, Schroder H, Stasch JP (2003) Mechanisms of nitric oxide independent activation of soluble guanylyl cyclase. Eur J Pharmacol 468:167–174PubMedCrossRef Schmidt P, Schramm M, Schroder H, Stasch JP (2003) Mechanisms of nitric oxide independent activation of soluble guanylyl cyclase. Eur J Pharmacol 468:167–174PubMedCrossRef
21.
Zurück zum Zitat Stasch JP, Schmidt PM, Nedvetsky PI et al (2006) Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest 116:2552–2561PubMedCrossRef Stasch JP, Schmidt PM, Nedvetsky PI et al (2006) Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest 116:2552–2561PubMedCrossRef
22.
Zurück zum Zitat Stasch JP, Schmidt P, Alonso-Alija C et al (2002) NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle. Br J Pharmacol 136:773–783PubMedCrossRef Stasch JP, Schmidt P, Alonso-Alija C et al (2002) NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle. Br J Pharmacol 136:773–783PubMedCrossRef
23.
Zurück zum Zitat Su J, Scholz PM, Weiss HR (2005) Differential effects of cGMP produced by soluble and particulate guanylyl cyclase on mouse ventricular myocytes. Exp Biol Med (Maywood) 230:242–250 Su J, Scholz PM, Weiss HR (2005) Differential effects of cGMP produced by soluble and particulate guanylyl cyclase on mouse ventricular myocytes. Exp Biol Med (Maywood) 230:242–250
24.
Zurück zum Zitat Suzuki T, Yamazaki T, Yazaki Y (2001) The role of the natriuretic peptides in the cardiovascular system. Cardiovasc Res 51:489–494PubMedCrossRef Suzuki T, Yamazaki T, Yazaki Y (2001) The role of the natriuretic peptides in the cardiovascular system. Cardiovasc Res 51:489–494PubMedCrossRef
25.
Zurück zum Zitat Yancy CW, Krum H, Massie BM et al (2008) Safety and efficacy of outpatient nesiritide in patients with advanced heart failure: results of the second follow-up serial infusions of nesiritide (FUSION II) trial. Circ Heart Fail 1:9–16CrossRef Yancy CW, Krum H, Massie BM et al (2008) Safety and efficacy of outpatient nesiritide in patients with advanced heart failure: results of the second follow-up serial infusions of nesiritide (FUSION II) trial. Circ Heart Fail 1:9–16CrossRef
26.
Zurück zum Zitat van der Zander K, Houben AJ, Hofstra L et al (2003) Hemodynamic and renal effects of low-dose brain natriuretic peptide infusion in humans: a randomized, placebo-controlled crossover study. Am J Physiol Heart Circ Physiol 285:H1206–H1212 van der Zander K, Houben AJ, Hofstra L et al (2003) Hemodynamic and renal effects of low-dose brain natriuretic peptide infusion in humans: a randomized, placebo-controlled crossover study. Am J Physiol Heart Circ Physiol 285:H1206–H1212
27.
Zurück zum Zitat Wilkins MR, Redondo J, Brown LA.(1997) The natriuretic-peptide family. Lancet 349(9061):1307–1310PubMedCrossRef Wilkins MR, Redondo J, Brown LA.(1997) The natriuretic-peptide family. Lancet 349(9061):1307–1310PubMedCrossRef
28.
Zurück zum Zitat Stasch JP, Schmidt PM, Nedvetsky PI et al (2006) Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest 116:2552–2561PubMedCrossRef Stasch JP, Schmidt PM, Nedvetsky PI et al (2006) Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest 116:2552–2561PubMedCrossRef
29.
Zurück zum Zitat Colucci WS, Elkayam U, Horton DP et al (2000) Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group. NEJM 343(4):246–253PubMedCrossRef Colucci WS, Elkayam U, Horton DP et al (2000) Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group. NEJM 343(4):246–253PubMedCrossRef
30.
Zurück zum Zitat Young JB et al. (2002) Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 287(12):1531–1540CrossRef Young JB et al. (2002) Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 287(12):1531–1540CrossRef
31.
Zurück zum Zitat Stasch JP, Schmidt P, Alonso-Alija C et al (2002) NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle. Br J Pharmacol 136:773–783PubMedCrossRef Stasch JP, Schmidt P, Alonso-Alija C et al (2002) NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle. Br J Pharmacol 136:773–783PubMedCrossRef
32.
Zurück zum Zitat Lapp H, Mitrovic V, Franz N et al (2009) Cinaciguat (BAY 58-2667) improves cardiopulmonary hemodynamics in patients with acute decompensated heart failure. Circulation 119(21):2781–2788PubMedCrossRef Lapp H, Mitrovic V, Franz N et al (2009) Cinaciguat (BAY 58-2667) improves cardiopulmonary hemodynamics in patients with acute decompensated heart failure. Circulation 119(21):2781–2788PubMedCrossRef
Metadaten
Titel
Neue Therapiekonzepte bei akut dekompensierter Herzinsuffizienz
verfasst von
Dr. S.A. Lehinant
V. Mitrovic
Publikationsdatum
01.09.2009
Verlag
D. Steinkopff-Verlag
Erschienen in
Intensivmedizin und Notfallmedizin / Ausgabe 6/2009
Print ISSN: 0175-3851
Elektronische ISSN: 1435-1420
DOI
https://doi.org/10.1007/s00390-009-0080-x

Weitere Artikel der Ausgabe 6/2009

Intensivmedizin und Notfallmedizin 6/2009 Zur Ausgabe

In eigener Sache

Für Sie gelesen

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.