Skip to main content
Log in

Systemic pressure-flow reactivity to norepinephrine in rabbits: impact of endotoxin and fluid loading

  • Experimental
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Objective

This study aimed to evaluate the impact of fluid loading on hemodynamics and vascular hypocontractility to norepinephrine (NE) in an endotoxic shock model.

Design

Mean arterial pressure (MAP), aortic blood flow velocity (AoV, 20 MHz Doppler) and aortic conductance (AoC = AoV/MAP) were studied during 180 min (T0–T180) in 41 anesthetized and ventilated rabbits.

Interventions

Shock was induced by a 600 µg/kg bolus injection of endotoxin. Fluid loading (20 ml/kg colloids) was infused from T90 to T120. Dose-response curves to NE were performed at TO, T60 and T120 in endotoxic and non-endotoxic animals with or without fluid loading.

Measurements and results

Endotoxin decreased pressure (−23 %, p<0.05) and flow (−42%, p<0.05) corresponding to a decrease in conductance (−19%, p<0.05). Fluid loading did not improve hypotension but markedly increased systemic flow (+51 %, p<0.01), corresponding to a hyperkinetic syndrome. Vascular reactivity to NE was impaired after endotoxin at T60 since the pressure response to NE was depressed (p<0.01) and flow did not decrease. In non-fluid-loaded groups, the pressure response to NE recovered at T120, with no reduction in flow. In fluid-loaded endotoxic animals, however, the pressure response to NE was still impaired at T120 (p<0.05), but with a decrease in flow.

Conclusions

Fluid loading transformed the hypodynamic profile of endotoxic shock into a hyperdynamic state without improving blood pressure. Depressed vascular reactivity to NE was observed in both hyperdynamic and hypodynamic states, suggesting that a reduced vascular reactivity does not necessarily imply systemic vasodilation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Caroll GC, Snyder JV (1982) Hyperdynamic severe intravascular sepsis depends on fluid administration in cynomolgus monkey. Am J Physiol 243: R131-R141

    Google Scholar 

  2. Dal Nogare AR (1991) Southwestern internal medicine conference: septic shock. Am J Med Sci 302: 50–65

    Article  Google Scholar 

  3. Natanson C, Fink MP, Ballantyne HK, MacVittie TJ, Conklin JJ, Parrillo JE (1986) Gramnegative bacteremia produces both severe systolic and diastolic cardiac dysfunction in a canine model that simulates human septic shock. J Clin Invest 78: 259–270

    Article  PubMed  CAS  Google Scholar 

  4. Suffredini AF, Fromm RE, Parker MM, Brenner M, Kovacs JA, Wesley RA, Parrillo JE (1989) The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med 321: 280–287

    PubMed  CAS  Google Scholar 

  5. Cryer HM, Garrison RN, Kaebnick HW, Harris PD, Flint LM (1987) Skeletal microcirculatory response to hyperdynamic Escherichia coli sepsis in unanesthetized rats. Arch Surg 122: 86–92

    PubMed  CAS  Google Scholar 

  6. Trank JW, Visscher MB (1962) Carotid sinus baroreceptor modifications associated with endotoxin shock. Am J Physiol 202: 971–977

    PubMed  CAS  Google Scholar 

  7. Breslow MJ, Miller CF, Parker SD, Walman AT, Traystman RJ (1987) Effect of vasopressor on organ blood flow during endotoxin shock in pigs. Am J Physiol 252: H291-H300

    PubMed  CAS  Google Scholar 

  8. Gray GA, Schott C, Julou-Schaeffer G, Fleming I, Parratt JR, Stoclet JC (1991) The effect of inhibitors of the L-arginine/nitric oxide pathway on endotoxin-induced loss of vascular responsiveness in anaesthetized rats. Br J Pharmacol 103:1218–1224

    PubMed  CAS  Google Scholar 

  9. Hollenberg SM, Cunnion RE, Zimmerberg J (1993) Nitric oxide synthase inhibition reverses arteriolar hyporesponsiveness to catecholamines in septic rats. Am J Physiol 264: H660-H663

    PubMed  CAS  Google Scholar 

  10. Schaller MD, Waebe B, Nussberger J, Brunner HR (1985) Angiotensin II, vasopressin, and sympathetic activity in conscious rats with endotoxemia. Am J Physiol 249: H1086-H1092

    PubMed  CAS  Google Scholar 

  11. Pastor C, Teisseire B, Vicaut E, Payen D (1994) Effects of L-arginine and L-nitro-arginine treatment on blood pressure and cardiac output in a rabbit endotoxin shock model. Crit Care Med 22: 465–469

    Article  PubMed  CAS  Google Scholar 

  12. Pastor CM, Losser MR, Payen D (1995) Nitric oxide donor prevents hepatic and systemic perfusion decrease induced by endotoxin in anesthetized rabbits. Hepatology 22:1547–1553

    PubMed  CAS  Google Scholar 

  13. Moncada S, Palmer MJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142

    PubMed  CAS  Google Scholar 

  14. Van der Linden P, Gilbart E, Engelman E, Schmartz D, De Rood M, Vincent JL (1990) Comparison of halothane, isoflurane, alfentanil and ketamine in experimental septic shock. Anesth Analg 70: 608–617

    PubMed  Google Scholar 

  15. Ottosson J, Dawidson I, Brandberg A, Idvall J, Sandor Z (1991) Cardiac output and organ blood flow in experimental septic shock: effect of treatment with antibiotics, corticosteroids, and fluid infusion. Circ Shock 35:14–24

    PubMed  CAS  Google Scholar 

  16. Noshima S, Noda H, Herndon DN, Traber LD, Traber DL (1993) Left ventricular performance during continuous endotoxin-induced hyperdynamic endotoxemia in sheep. J Appl Physiol 74: 1528–1533

    PubMed  CAS  Google Scholar 

  17. Bressack MA, Morton NS, Hortop J (1987) Group B streptococcal sepsis in the piglet: effects of fluid therapy on venous return, organ edema, and organ blood flow. Circ Res 61: 659–669

    PubMed  CAS  Google Scholar 

  18. Julou-Schaeffer G, Gray GA, Fleming I, Schott C, Parratt JR, Stoclet JC (1990) Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway. Am J Physiol 259: H1038-H1043

    PubMed  CAS  Google Scholar 

  19. Suba EA, McKenna TM, Williams TJ (1992) In vivo and in vitro effects of endotoxin on vascular responsiveness to norepinephrine and signal transduction in the rat. Circ Shock 36:127–133

    PubMed  CAS  Google Scholar 

  20. Fleming I, Julou-Schaeffer G, Gray AG, Parratt JR, Stoclet JC (1991) Evidence that an L-arginine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin. Br J Pharmacol 103:1047–1052

    PubMed  CAS  Google Scholar 

  21. Losser MR, Bernard C, Beaudeux JL, Pison C, Payen D (1997) Glucose modulates hemodynamic, metabolic and inflammatory response to lipopolysac-charide in rabbits. J Appl Physiol 83: 1566–1574

    PubMed  CAS  Google Scholar 

  22. Cholley BP, Lang RM, Berger DS, Korcarz C, Payen D, Shroff SG (1995) Alterations in systemic arterial mechanical properties during septic shock: role of fluid resuscitation. Am J Physiol 269: H375-H384

    PubMed  CAS  Google Scholar 

  23. Hartley CJ, Cole JS (1974) An ultrasonic pulsed Doppler system for measuring blood flow in small vessels. Am J Physiol 37: 626–629

    CAS  Google Scholar 

  24. Frot C, Payen D (1996) Indications du remplissage vasculaire dans le choc septique. Reanim Urg 5: 467–472

    Article  Google Scholar 

  25. Lautt W (1989) Resistance or conductance for expression of arterial vascular tone. Microvasc Res 37: 230–236

    Article  PubMed  CAS  Google Scholar 

  26. Stinnett HO, Bishop VS, Peterson DF (1976) Reduction in baroreflex cardiovascular response due to venous infusion in the rabbit. Circ Res 39: 766–772

    PubMed  CAS  Google Scholar 

  27. Karzai W, Reilly JM, Hoffman WD, Cunnion RE, Danner RL, Banks SM, Parrillo JE, Natanson C (1995) Hemodynamic effects of dopamine, norepinephrine, and fluids in a dog model of sepsis. Am J Physiol 268: H692-H702

    PubMed  CAS  Google Scholar 

  28. Ellman H (1984) Capillary permeability in septic patients. Crit Care Med 12: 629–633

    Article  PubMed  CAS  Google Scholar 

  29. Matsuda TC, Eccleston CA, Rubinstein I, Rennard SI, Joyner WL (1991) Antioxidants attenuate endotoxin-induced microvascular leakage of macromolecules in vivo. J Appl Physiol 70: 1483–1489

    Article  PubMed  CAS  Google Scholar 

  30. Gray GA, Furman BL, Parratt JR (1990) Endotoxin-induced impairment of vascular reactivity in the pithed rat: role of arachidonic acid metabolites. Circ Shock 31: 395–406

    PubMed  CAS  Google Scholar 

  31. Bernard C, Szekely B, Philip Y, Payen D, Tedgui A (1992) Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release. J Clin Invest 89: 851–860

    Article  PubMed  CAS  Google Scholar 

  32. Beasley D, Cohen RA, Levinski NG (1990) Endotoxin inhibits contraction of vascular smooth muscle in vitro. Am J Physiol 258: H1187-H1192

    PubMed  CAS  Google Scholar 

  33. Mc Kenna TM (1990) Prolonged exposure of rat aorta to low levels of endotoxin in vitro results in impaired contractility. J Clin Invest 86:160–168

    Article  CAS  Google Scholar 

  34. Mc Kenna TM (1992) Recovery of vascular tissue contractile function during sustained endotoxin exposure. Am J Physiol 263: H1628–1631

    CAS  Google Scholar 

  35. Desjars P, Pinaud M, Potel G, Tasseau F, Touze MD (1987) A reappraisal of norepinephrine therapy in human septic shock. Crit Care Med 15:134–137

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Pay.

Additional information

This work was supported by grants from Paris VII University and the “Direction de la Recherche et de l’Enseignement Doctoral (DRED)”

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ricard-Hibon, A., Losser, M.R., Kong, R. et al. Systemic pressure-flow reactivity to norepinephrine in rabbits: impact of endotoxin and fluid loading. Intensive Care Med 24, 959–966 (1998). https://doi.org/10.1007/s001340050696

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s001340050696

Key words

Navigation