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Modulation adrénergique et défaillance cardiaque au cours du sepsis: intérêt des bêtabloquants

Adrenergic modulation and heart failure during sepsis: place of beta-blockers

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Réanimation

Résumé

Malgré les progrès thérapeutiques récents, le choc septique conserve une mortalité trop élevée. Le système adrénergique est un modulateur clé du fonctionnement des organes et de l’homéostasie cardiovasculaire. Il pourrait être une nouvelle cible thérapeutique intéressante dans cette pathologie. La régulation β-adrénergique de la fonction immunitaire dans le sepsis est complexe et dépend du temps. Toutefois, l’activation β2 ainsi que le blocage β1 exercent un effet protecteur contre la réponse pro-inflammatoire, en modulant le profil de production de cytokines. Le blocage β1 améliore l’homéostasie cardiovasculaire chez les animaux septiques, en abaissant la consommation d’oxygène du myocarde sans altérer la perfusion des organes. Il pourrait également avoir des effets antiapoptotiques. Par conséquent, les bêtabloquants, comme ils le font dans l’insuffisance cardiaque non septique, pourraient participer à l’amélioration de la dysfonction cardiovasculaire au cours du sepsis.

Abstract

Despite recent therapeutic progress, sepsis is still responsible for unacceptably high mortality rates. The adrenergic system, a key modulator of organ function and cardiovascular homeostasis, may be an interesting new therapeutic target for septic shock. β-adrenergic regulation of the immune function in sepsis is complex and time-dependent. However, β2 activation as well as β1 blockade seem to downregulate the pro-inflammatory response by modulating the cytokine production profile. β1 blockade improves cardiovascular homeostasis in septic animals by lowering myocardial oxygen consumption without altering organ perfusion, and perhaps by restoring normal cardiovascular variability. β-blockers may also be of interest in the systemic catabolic response to sepsis, as they counteract epinephrine, which is known to promote hyperglycemia as well as lipid and protein catabolism. β1 blockade, and β2 activation improve sepsis-induced immune, cardiovascular, and coagulation dysfunctions. However, β2 blockade seems beneficial regarding metabolism. Enough evidence has been accumulated in the literature to propose β-adrenergic modulation, β1 blockade, and β2 activation in particular, as new promising therapeutic targets for septic dyshomeostasis, altering favourably immune, cardiovascular, metabolic, and coagulation systems.

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Références

  1. Kirstein SL, Insel PA (2004) Autonomic nervous system pharmacogenomics: a progress report. Pharmacol Rev 56:31–52

    Article  PubMed  CAS  Google Scholar 

  2. Emorine LJ, Marullo S, Briend-Sutren MM, et al (1989) Molecular characterization of the human beta3-adrenergic receptor. Science 245:1118–1121

    Article  PubMed  CAS  Google Scholar 

  3. Ahlquist RP (1973) Adrenergic receptors: a personal and practical view. Perspect Biol Med 17: 119–122

    PubMed  CAS  Google Scholar 

  4. Cohn JN, Levine TB, Olivari MT, et al (1984) Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 311:819–823

    Article  PubMed  CAS  Google Scholar 

  5. Reiter E, Lefkowitz RJ (2006) GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling. Trends Endocrinol Metab 17:159–165

    Article  PubMed  CAS  Google Scholar 

  6. Tsao PI, von Zastrow M (2000) Type-specific sorting of G protein-coupled receptors after endocytosis. J Biol Chem 275:11130–11140

    Article  PubMed  CAS  Google Scholar 

  7. Broadley KJ (1999) Review of mechanisms involved in the apparent differential desensitization of beta1- and beta2-adrenoceptormediated functional responses. J Auton Pharmacol 19:335–345

    Article  PubMed  CAS  Google Scholar 

  8. Olivetti G, Abbi R, Quaini F, et al (1997) Apoptosis in the failing human heart. N Engl J Med 336:1131–1141

    Article  PubMed  CAS  Google Scholar 

  9. Zaugg M, Xu W, Lucchinetti E, et al (2000) β-adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes. Circulation 102:344–350

    PubMed  CAS  Google Scholar 

  10. Zhu WZ, Wang SQ, Chakir K, et al (2003) Linkage of beta1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/calmodulin kinase II. J Clin Invest 111:617–625

    PubMed  CAS  Google Scholar 

  11. Zheng M, Han QD, **ao RP (2004) Distinct beta-adrenergic receptor subtype signaling in the heart and their pathophysiological relevance. Sheng Li Xue Bao 56:1–15

    PubMed  CAS  Google Scholar 

  12. Zhu WZ, Zheng M, Koch WJ, et al (2001) Dual modulation of cell survival and cell death by beta2-adrenergic signaling in adult mouse cardiac myocytes. Proc Natl Acad Sci USA 98:1607–1612

    Article  PubMed  CAS  Google Scholar 

  13. Finkel MS, Oddis CV, Jacob TD, et al (1992) Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257:387–389

    Article  PubMed  CAS  Google Scholar 

  14. Tang C, Liu MS (1996) Initial externalization followed by internalization of beta-adrenergic receptors in rat heart during sepsis. Am J Physiol 270:R254–R263

    PubMed  CAS  Google Scholar 

  15. Balligand JL, Ungureanu D, Kelly RA, et al (1993) Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium. J Clin Invest 91:2314–2319

    Article  PubMed  CAS  Google Scholar 

  16. Kumar A, Brar R, Wang P, et al (1999) Role of nitric oxide and cGMP in human septic serum-induced depression of cardiac myocyte contractility. Am J Physiol 276:R265–R276

    PubMed  CAS  Google Scholar 

  17. Wu LL, Yang SL, Yang RC, et al (2003) G-protein and adenylate cyclase complex-mediated signal transduction in the rat heart during sepsis. Shock 19:533–537

    Article  PubMed  CAS  Google Scholar 

  18. Matsuda N, Hattori Y, Akaishi Y, et al (2000) Impairment of cardiac beta-adrenoceptor cellular signaling by decreased expression of G(s alpha) in septic rabbits. Anesthesiology 93:1465–1473

    Article  PubMed  CAS  Google Scholar 

  19. Borovikova LV, Ivanova S, Zhang M, et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462

    Article  PubMed  CAS  Google Scholar 

  20. Grisanti LA, Evanson J, Marchus E, et al (2010) Pro-inflammatory responses in human monocytes are beta1-adrenergic receptor subtype dependent. Mol Immunol 47:1244–1254

    Article  PubMed  CAS  Google Scholar 

  21. Tracey KJ (2011) Cell biology. Ancient neurons regulate immunity. Science 332:673–674

    CAS  Google Scholar 

  22. Sharshar T, Gray F, Lorin de la Grandmaison G, et al (2003) Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet 362:1799–1805

    Article  PubMed  CAS  Google Scholar 

  23. Pontet J, Contreras P, Curbelo A, et al (2003) Heart rate variability as early marker of multiple organ dysfunction syndrome in septic patients. J Crit Care 18:156–163

    Article  PubMed  Google Scholar 

  24. Goldstein B, Kempski MH, Stair D, et al (1995) Autonomic modulation of heart rate variability during endotoxin shock in rabbits. Crit Care Med 23:1694–1702

    Article  PubMed  CAS  Google Scholar 

  25. Annane D, Trabold F, Sharshar T, et al (1999) Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach. Am J Respir Crit Care Med 160:458–465

    PubMed  CAS  Google Scholar 

  26. Aboab J, Polito A, Orlikowski D, et al (2008) Hydrocortisone effects on cardiovascular variability in septic shock: a spectral analysis approach. Crit Care Med 36:1481–1486

    Article  PubMed  CAS  Google Scholar 

  27. Schmidt H, Müller-Werdan U, Hoffmann T, et al (2005) Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups. Crit Care Med 33:1994–2002

    Article  PubMed  Google Scholar 

  28. Seely AJ, Christou NV (2000) Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems. Crit Care Med 28:2193–2200

    Article  PubMed  CAS  Google Scholar 

  29. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 93:1043–1065

    Article  Google Scholar 

  30. Chess GF, Tam RM, Calaresu FR (1975) Influence of cardiac neural inputs on rhythmic variations of heart period in the cat. Am J Physiol 228:775–780

    PubMed  CAS  Google Scholar 

  31. Pichot V, Gaspoz JM, Molliex S, et al (1999) Wavelet transform to quantify heart rate variability and to assess its instantaneous changes. J Appl Physiol 86:1081–1091

    PubMed  CAS  Google Scholar 

  32. Goldberger AL (1996) Non-linear dynamics for clinicians: chaos theory, fractals, and complexity at the bedside. Lancet 347:1312–1314

    Article  PubMed  CAS  Google Scholar 

  33. Hon EH, Lee ST (1965) The fetal electrocardiogram. Am J Obstet Gynecol 91:56–60

    PubMed  CAS  Google Scholar 

  34. La Rovere MT, Bigger JT Jr, Marcus FI, et al (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction). Lancet 351:478–484

    PubMed  Google Scholar 

  35. Fauchier L, Babuty D, Cosnay P, et al (1997) Heart rate variability in idiopathic dilated cardiomyopathy: characteristics and prognostic value. J Am Coll Cardiol 30:1009–1014

    Article  PubMed  CAS  Google Scholar 

  36. Harasawa Y, Imaizumi T, Ando S, et al (1994) Influence of arotinolol hydrochloride on heart rate spectrum in hypertensive subjects. Jpn Circ J 58:326–337

    Article  PubMed  CAS  Google Scholar 

  37. Hjalmarson A, Goldstein S, Fagerberg B, et al (2000) Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. JAMA 283:1295–1302

    CAS  Google Scholar 

  38. Ackland GL, Yao ST, Rudiger A, et al (2010) Cardioprotection, attenuated systemic inflammation, and survival benefit of beta1-adrenoceptor blockade in severe sepsis in rats. Crit Care Med 38:388–394

    Article  PubMed  CAS  Google Scholar 

  39. Sloan RP, McCreath H, Tracey KJ, et al (2007) RR interval variability is inversely related to inflammatory markers: the CARDIA study. Mol Med 13:178–184

    PubMed  Google Scholar 

  40. Jan BU, Coyle SM, Macor MA, et al (2010) Relationship of basal heart rate variability to in vivo cytokine responses after endotoxin exposure. Shock 33:363–368

    Article  PubMed  CAS  Google Scholar 

  41. Piepoli M, Garrard CS, Kontoyannis DA, et al (1995) Autonomic control of the heart and peripheral vessels in human septic shock. Intensive Care Med 21:112–119

    Article  PubMed  CAS  Google Scholar 

  42. Schmidt H, Müller-Werdan U, Hoffmann T, et al (2005) Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups. Crit Care Med 33:1994–2002

    Article  PubMed  Google Scholar 

  43. Suzuki T, Morisaki H, Serita R, et al (2005) Infusion of the betaadrenergic blocker esmolol attenuates myocardial dysfunction in septic rats. Crit Care Med 33:2294–2301

    Article  PubMed  CAS  Google Scholar 

  44. Braunwald E, Chidsey CA, Harrison DC, et al (1963) Studies on the function of the adrenergic nerve endings in the heart. Circulation 28:958–969

    PubMed  CAS  Google Scholar 

  45. Epstein SE (1967) Clinical and hemodynamic appraisal of betaadrenergic blocking drugs. Ann NY Acad Sci 139:952–967

    Article  PubMed  CAS  Google Scholar 

  46. Haft JI (1974) Cardiovascular injury induced by sympathetic catecholamines. Prog Cardiovasc Dis 17:73–86

    Article  PubMed  CAS  Google Scholar 

  47. Bristow MR, Ginsburg R, Minobe W, et al (1982) Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med. 307:205–211

    Article  PubMed  CAS  Google Scholar 

  48. Waagstein F, Hjalmarson A, Varnauskas E, et al (1975) Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J 37:1022–1036

    Article  PubMed  CAS  Google Scholar 

  49. Heilbrunn SM, Shah P, Bristow MR, et al (1989) Increased beta-receptor density and improved hemodynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy. Circulation 79:483–490

    Article  PubMed  CAS  Google Scholar 

  50. Leineweber K, Rohe P, Beilfuss A, et al (2005) G-protein-coupled receptor kinase activity in human heart failure: effects of β-adrenoceptor blockade. Cardiovasc Res 66:512–519

    Article  PubMed  CAS  Google Scholar 

  51. Mortara A, La Rovere MT, Pinna GD, et al (2000) Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure. J Am Coll Cardiol 36:1612–1618

    Article  PubMed  CAS  Google Scholar 

  52. Berk JL, Hagen JF, Beyer WH, et al (1969) The treatment of endotoxin shock by beta-adrenergic blockade. Ann Surg 169:74–81

    Article  PubMed  CAS  Google Scholar 

  53. Oberbeck R, Schmitz D, Wilsenack K, et al (2004) Adrenergic modulation of survival and cellular immune functions during polymicrobial sepsis. Neuroimmunomodulation 11:214–223

    Article  PubMed  CAS  Google Scholar 

  54. Elenkov IJ, Wilder RL, Chrousos GP, et al (2000) The sympathetic nerve — an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 52:595–638

    PubMed  CAS  Google Scholar 

  55. Aboab J, Sebille V, Jourdain M, et al (2011) Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock. Intensive Care Med 37:1344–1351

    Article  PubMed  CAS  Google Scholar 

  56. Herndon DN, Hart DW, Wolf SE, et al (2001) Reversal of catabolism by beta-blockade after severe burns. N Engl J Med 345:1223–1229

    Article  PubMed  CAS  Google Scholar 

  57. Christensen S, Johansen MB, Tønnesen E, et al (2011) Preadmission beta-blocker use and 30-day mortality among patients in intensive care: a cohort study. Crit Care 15:R87

    Article  PubMed  Google Scholar 

  58. Noveanu M, Breidthardt T, Reichlin T, et al (2010) Effect of oral beta-blocker on short and long-term mortality in patients with acute respiratory failure: results from the BASEL-II-ICU study. Crit Care 14:R198

    Article  PubMed  Google Scholar 

  59. Böhm M, Link A, Cai D, et al (2011) Beneficial association of β-blocker therapy on recovery from severe acute heart failure treatment: data from the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support trial. Crit Care 39:940–944

    Article  Google Scholar 

  60. Gore DC, Wolfe RR (2006) Hemodynamic and metabolic effects of selective beta1-adrenergic blockade during sepsis. Surgery 139:686–694

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Service de réanimation, hôpital Raymond-Poincaré, AP-HP, université de Versailles-Saint-Quentin, 104, boulevard Raymond-Poincaré, F-92380, Garches, France

    J. Aboab & D. Annane

  2. Laboratoire d’étude de la réponse neuroendocrine au sepsis, EA 4342, université de Versailles-Saint-Quentin, Garches, France

    J. Aboab, E. de Montmollin, A. Mansart & D. Annane

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  1. J. Aboab
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Correspondence to D. Annane.

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Aboab, J., de Montmollin, E., Mansart, A. et al. Modulation adrénergique et défaillance cardiaque au cours du sepsis: intérêt des bêtabloquants. Réanimation 21, 171–179 (2012). https://doi.org/10.1007/s13546-012-0455-z

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