Advertisement

Intensive Care Medicine

, Volume 19, Issue 2, pp 99–104 | Cite as

Plasma cyclic guanosine 3′–5′ monophosphate concentrations and low vascular resistance in human septic shock

  • F. Schneider
  • Ph. Lutun
  • A. Couchot
  • P. Bilbault
  • J. D. Tempé
Originals

Abstract

Objective

To investigate the increase in plasma cyclic GMP (cGMP) concentrations in humans with hyperkinetic septic shock (SS) and to evaluate its relationship to low systemic vascular resistance (SVR).

Design

Prospective clinical investigation.

Setting

Medical intensive care unit of a university hospital.

Patients

22 patients with documented SS requiring hemodynamic resuscitation, respiratory support and —in some cases — hemodialysis.

Measurements and results

Hemodynamic data were recorded at admission time and then twice a-day during the following 72 h. We simultaneously measured cyclic GMP, atrial natriuretic peptides (ANP), creatininemia and platelet counts. At admission time, higher plasma cGMP concentrations were observed in patients with SS (11.84±1.52 pmol·ml−1) than in healthy controls (1.77±0.18 pmol·ml−1,p<0.0001), in septicemia patients without circulatory failure (3.28±0.36 pmol·ml−1,p<0.005) or in patients with hyperkinetic non-septic shock (3.6±0.7 pmol·ml−1,p<0.02). In contrast, there was no significant difference between patients with SS and controls with anuria from non-septic origin. Also ANP concentrations were higher in patients with SS than in others. In addition, cGMP levels correlated negatively with SVR during the first 48 h of the study, and positively with creatininemia later when renal function worsened. However, they did not correlate significantly with ANP.

Conclusion

These data demonstrate that a significant increase in plasma cGMP concentrations occurs during human SS and that it correlates with the decline in peripheral vascular resistance in the absence, but not in the presence, of severe renal failure. Furthermore, the increase in cGMP levels cannot be ascribed solely to enhanced ANP-induced particulate guanylyl cyclase activity. Thus, our results suggest the occurrence of another endogenous source of cGMP during hyperkinetic SS.

Key words

Septic shock Cyclic GMP Guanylyl cyclase Human Atrial natriuretic peptide Vascular resistance 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Paratt JR (1989) Alterations in vascular reactivity in sepsis and endotoxemia. In: Vincent JL (ed) Update in intensive care and emergency medicine. Springer, Berlin Heidelberg New York Tokyo, pp 299–308Google Scholar
  2. 2.
    Tedgui A, Bernard C (1991) Interactions between cytokines and vascular wall: effect on the contractile function. In: Vincent JL (ed) Update in intensive care and emergency medicine. Springer, Berlin Heidelberg New York Tokyo, pp 213–222Google Scholar
  3. 3.
    Palmer RMJ, Ferridje AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature (London) 327:524–526Google Scholar
  4. 4.
    Julou-Schaeffer G, Gray GA, Fleming I et al (1990) Loss of vascular responsiveness induced by endotoxin involves the L-arginine pathway. Am J Physiol 259:H 1038-H 1043Google Scholar
  5. 5.
    Knowles RG, Merett M, Salter M et al (1990) Differential induction of brain, lung and liver nitric oxide synthase by endotoxin in the rat. Biochem J 270:833–836Google Scholar
  6. 6.
    Debbie B (1990) Interleukin 1 and endotoxin activate soluble guanylate cyclase in vascular smooth muscle. Am J Physiol 259:R38-R44Google Scholar
  7. 7.
    Lonchampt MO, Auguet M, Delafotte S et al (1992) Lipoteichoic acid: a new inducer of NO synthase. In: Proceedings of the Second International Symposium on Endothelium-Derived Vasoactive Factors, Basel (Abstract)Google Scholar
  8. 8.
    Busse R, Kaufmann H, Mulsch A (1991) Inducible NO synthase in the human vasculature. In: Proceedings of the Second Conference on Nitric Oxide, London (Abstract)Google Scholar
  9. 9.
    Schulz S, Yven PST, Garbers DL (1991) The expanding family of guanylyl cyclases. TIPS 12:116–120Google Scholar
  10. 10.
    Arnold WP, Mittal CK, Katsuki S et al (1977) Nitric oxide activates guanylate cyclase and increases guanosine 3′5′ cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci USA 74:3203–3207Google Scholar
  11. 11.
    Schini V, Schoeffter P, Miller RC (1989) Effect of endothelium on basal and on stimulated accumulation and efflux of cyclic GMP in rat isolated aorta. Br J Pharmacol 97:853–865Google Scholar
  12. 12.
    Huntsman LL, Steward DK, Barnes SR et al (1983) Non-invasive Doppler determination of cardiac output in man: clinical validation. Circulation 67:593–602Google Scholar
  13. 13.
    Meyer RA, Kalavathy A, Korfhagen JC, Kaplan S (1982) Limitations of Doppler echocardiography in the calculation of cardiac output. Circulation 66 [Suppl 2]:122Google Scholar
  14. 14.
    Schuller F, Fleming I, Stoclet JC et al (1992) Plasmatic cyclic GMP is not a direct index of L-arginine/nitric oxide pathway activation by endotoxin. Eur J Pharmacol 212:93–96Google Scholar
  15. 15.
    Hamet P, Tremblay J, Genest M et al (1984) Effect of native and synthetic ANF on cyclic GMP. Biochem Biophys Res Commun 123:515–527Google Scholar
  16. 16.
    Münzel T, Drexler H, Holtz J, Kurtz S, Just H (1991) Mechanisms involved in the response to prolonged infusion of atrial natriuretic factor in patients with chronic heart failure. Circulation 33:191–201Google Scholar
  17. 17.
    Vorderwinkler KP, Artner-Dworzak E, Jakobs G et al (1991) Release of cyclic guanosine monophosphate evaluated as a diagnostic tool in cardiac diseases. Clin Chem 37:168–190Google Scholar
  18. 18.
    Waldman SA, Rapoport RM, Murad F (1984) ANF selectively activates particulate guanylate cyclase and elevates cyclic GMP in rat tissues. J Biol Chem 259:14332–14334Google Scholar
  19. 19.
    Shirasaki S (1986) Effect of endotoxin shock on plasma levels of immunoreactive atrial natriuretic polypeptide and stress hormones in dogs. Masui 35:1650–1655Google Scholar
  20. 20.
    Kelm M, Feelisch M, Deussen A et al (1991) Release of endothelium derived nitric oxide in relation to pressure and flow. Cardiovasc Res 25:831–836Google Scholar
  21. 21.
    Lowe DW, Chang MS, Goeddel DV et al (1989) Human ANF receptor defines a new paradigm for second messenger transduction. EMBO J 8:1377–1384Google Scholar
  22. 22.
    Field M, Graf LH, Laird WJ et al (1978) Heat stable enterotoxin ofE. coli: in vitro effects on guanylate cyclase activity, cGMP concentration and ion transport in small intestine. Proc Natl Acad Sci USA 75:2800–2804Google Scholar
  23. 23.
    Katsuki S, Arnold W, Mittel C et al (1977) Stimulation of guanylate cyclase by sodium nitroprussiate, nitroglycerol and nitric oxide in various tissue preparations and comparison to the effect of sodium azide and hydroxylysine. J Cyclic Nucleotide Res 3:23–25Google Scholar
  24. 24.
    Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142Google Scholar
  25. 25.
    Roy LF, Ogilvie RI, Larochelle P et al (1989) Cardiac and vascular effects of atrial natriuretic factor and sodium nitroprusside in healthy men. Circulation 79:383–392Google Scholar
  26. 26.
    Schneider F, Lutun P, Hasselmann M, Stoclet JC, Tempé JD (1992) Methylene blue increases systemic vascular resistance in human septic shock. Intensive Care Med 18:309–311Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • F. Schneider
    • 1
  • Ph. Lutun
    • 1
  • A. Couchot
    • 1
  • P. Bilbault
    • 1
  • J. D. Tempé
    • 1
  1. 1.Service de Réanimation Médicale, Hôpital de HautepierreHôpitaux Universitaires de StrasbourgStrasbourgFrance

Personalised recommendations