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New approach to an ovine model of hypodynamic endotoxaemia

Published online by Cambridge University Press:  23 December 2004

M. Westphal ,
F. Daudel ,
H. G. Bone ,
H. Van Aken ,
J. Sander ,
H. Stubbe  and
M. Booke
M. Westphal
Affiliation:
University of Münster, Department of Anaesthesiology and Intensive Care, Münster, Germany
F. Daudel
Affiliation:
University of Münster, Department of Anaesthesiology and Intensive Care, Münster, Germany
H. G. Bone
Affiliation:
University of Münster, Department of Anaesthesiology and Intensive Care, Münster, Germany
H. Van Aken
Affiliation:
University of Münster, Department of Anaesthesiology and Intensive Care, Münster, Germany
J. Sander
Affiliation:
University of Münster, Department of Anaesthesiology and Intensive Care, Münster, Germany
H. Stubbe
Affiliation:
University of Münster, Department of Anaesthesiology and Intensive Care, Münster, Germany
M. Booke
Affiliation:
Kliniken des Main-Taunus-Kreises GmbH, Department of Anaesthesiology, Bad Soden am Taunus, Germany
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Abstract

Summary

Background and objective: Since the moribund hypodynamic phase of septic shock has primarily been studied in small animal models, the objective of this study was to investigate the usefulness of infusing Salmonella typhosa endotoxin at incrementing doses to establish an ovine model of hypodynamic endotoxaemia.

Methods: In a prospective laboratory experiment, eight adult ewes were instrumented for a chronic study. Following a baseline measurement in the healthy state, a continuous endotoxin infusion was started with 10 ng kg−1 min−1 and was doubled every hour seven times. Haemodynamics, key variables of oxygen transport, and arterial lactate concentrations were determined every hour.

Results: In a dose-dependent manner, endotoxin infusion caused pulmonary hypertension, decreased cardiac output and mean arterial pressure, increased heart rate, and to a certain extent, systemic vascular resistance index. Following 4 h of endotoxaemia, the maximum decrease in cardiac output occurred (4.8 ± 0.2 vs. 7.6 ± 0.3L min−1; P < 0.001). This was accompanied by tissue dysoxia, represented by decreases in oxygen delivery (797 ± 20 vs. 1041 ± 28 mL min−1), oxygen consumption (277 ± 14 vs. 396 ± 15 mL min−1) and oxygen extraction rate (0.35 ± 0.01 vs. 0.38 ± 0.01%; each P < 0.01), as well as an increase in arterial lactate concentration (1.7 ± 0.1 vs. 0.7 ± 0.1 mmol L−1; P < 0.05).

Conclusions: This large animal model may be helpful to study the pathophysiology responsible for cardiovascular failure, and also new therapeutic approaches relevant to management of hypodynamic circulation in the common setting of progressed systemic inflammation.

Keywords

ANIMAL, sheepENDOTOXAEMIASHOCK, SEPTIC, hypodynamic
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 21 , Issue 8 , August 2004 , pp. 625 - 631
Copyright
2004 European Society of Anaesthesiology

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References

Latifi SQ, O’Riordan MA, Levine AD. Interleukin-10 controls the onset of irreversible septic shock. Infect Immun 2002; 70: 4441–4446.Google Scholar
Vallet B. Endothelial cell dysfunction and abnormal tissue perfusion. Crit Care Med 2002; 30: 229–234.Google Scholar
Suzuki N, Sakamoto A, Ogawa R. Effect of L-canavanine, an inhibitor of inducible nitric oxide synthase, on myocardial dysfunction during septic shock. J Nippon Med Sch 2002; 69: 13–18.Google Scholar
Mosi R, Seguin B, Cameron B, Amankwa L, Darkes MC, Fricker SP. Mechanistic studies on AMD6221: a ruthenium-based nitric oxide scavanger. Biochem Biophys Res Commun 2002; 29: 519–529.Google Scholar
Landry DW, Oliver JA. The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog. J Clin Invest 1992; 89: 2071–2074.Google Scholar
Schoemaker WC, Appel PL, Kram HB, Bishop MH, Abraham E. Sequence of physiologic patterns in surgical septic shock. Crit Care Med 1993; 21: 1876–1889.Google Scholar
Meyer J, Booke M, Waurick R, Prien T, Van Aken H. Nitric oxide synthase inhibition restores vasopressor effects of norepinephrine in ovine hyperdynamic sepsis. Anesth Analg 1996; 83: 1009–1013.Google Scholar
Westphal M, Stubbe H, Bone HG, et al. Hemodynamic effects of exogenous adrenomedullin in healthy and endotoxemic sheep. Biochem Biophys Res Commun 2002; 296: 134–138.Google Scholar
Scharte M, Meyer J, Van Aken H, Bone HG. Hemodynamic effects of terlipressin (a synthetic analog of vasopressin) in healthy and endotoxemic sheep. Crit Care Med 2001; 29: 1756–1760.Google Scholar
Sielenkämper AW, Yu P, Eichelbrönner O. Diaspirin cross-linked Hb and norepinephrine prevent the sepsis-induced increase in critical O2 delivery. Am J Physiol Heart Circ Physiol 2000; 279: H1922–H1930.Google Scholar
Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Crit Care Med 1999; 27: 639–660.
Masouye K, Gunning K, Pittlet JF, Suter PM, Morel DR. Xanthine derivative HWA 138 attenuates hemodynamic and oxygen uptake dysfunction secondary to severe endotoxin shock in sheep. Circ Shock 1992; 36: 113–119.Google Scholar
Bahrami S, Yao YM, Shiga H, Leichtfried G, Redl H, Schlag G. Comparison of the efficacy of pentoxyfylline and albifyllin (HWA 138) on endotoxin-induced cytokine production, coagulation disturbances, and mortality. Shock 1996; 6: 424–428.Google Scholar
Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. New Engl J Med 2001; 23: 588–595.Google Scholar
Koo DJ, Zhou M, Chaudry IH, Wang P. The role of adrenomedullin in producing differential hemodynamic responses during sepsis. J Surg Res 2001; 95: 207–218.Google Scholar
Ornan DA, Chaudry IH, Wang P. Pulmonary clearance of adrenomedullin is reduced during the late stage of sepsis. Biochim Biophys Acta 1999; 1427: 315–321.Google Scholar
Ricard-Hibon A, Losser MR, Kong R, Beloucif S, Teisseire B, Payen D. Systemic pressure-flow reactivity to norepinephrine in rabbits: impact of endotoxin and fluid loading. Intensive Care Med 1998; 24: 959–966.Google Scholar
Booke M, Traber LD, Traber DL. Development of effective therapies for sepsis. Crit Care Med 1995; 23: 1305–1306.Google Scholar
VanderMeer TJ, Wang H, Fink MP. Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock. Crit Care Med 1995; 23: 1217–1226.Google Scholar
Mitaka C, Hirata Y, Yokoyama K, Makita K, Imai T. A selective inhibitor for inducible nitric oxide synthase improves hypotension and lactic acidosis in canine endotoxic shock. Crit Care Med 2001; 29: 2156–2161.Google Scholar
Mitaka C, Hirata Y, Yokoyama K, Makita K, Imai T. S-methylisothiourea sulfate improves renal, but not hepatic dysfunction in canine endotoxic shock model. Intensive Care Med 2001; 26: 117–124.Google Scholar
Shatney CH, Read G. Another unacceptable model of primate septic shock. Adv Shock Res 1981; 6: 1–13.Google Scholar
Halmagyi DF, Gillet DJ. Norepinephrine response in normal and hypotensive sheep. J Appl Physiol 1966; 21: 1261–1264.Google Scholar