Top

Intensive Care Medicine

Published in:

Open Access 01-09-2011 | Experimental

The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats

Authors: Matthieu Legrand, Rick Bezemer, Asli Kandil, Cihan Demirci, Didier Payen, Can Ince

Published in: Intensive Care Medicine | Issue 9/2011

Abstract

Purpose

To study the role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats.

Methods

Rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 6), a group in which LPS administration was followed by immediate fluid resuscitation which prevented the drop of renal blood flow (EARLY group) (n = 6), and a group in which LPS administration was followed by delayed (i.e., a 2-h delay) fluid resuscitation (LATE group) (n = 6). Renal blood flow was measured using a transit-time ultrasound flow probe. Microvascular perfusion and oxygenation distributions in the renal cortex were assessed using laser speckle imaging and phosphorimetry, respectively. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were measured as markers of systemic inflammation. Furthermore, renal tissue samples were stained for leukocyte infiltration and inducible nitric oxide synthase (iNOS) expression in the kidney.

Results

LPS infusion worsened both microvascular perfusion and oxygenation distributions. Fluid resuscitation improved perfusion histograms but not oxygenation histograms. Improvement of microvascular perfusion was more pronounced in the EARLY group compared with the LATE group. Serum cytokine levels decreased in the resuscitated groups, with no difference between the EARLY and LATE groups. However, iNOS expression and leukocyte infiltration in glomeruli were lower in the EARLY group compared with the LATE group.

Conclusions

In our model, prevention of endotoxemia-induced systemic hypotension by immediate fluid resuscitation (EARLY group) did not prevent systemic inflammatory activation (IL-6, IL-10, TNF-α) but did reduce renal inflammation (iNOS expression and glomerular leukocyte infiltration). However, it could not prevent reduced renal microvascular oxygenation.

Available only for authorised users

Bagshaw SM, George C, Bellomo R (2007) Changes in the incidence and outcome for early acute kidney injury in a cohort of Australian intensive care units. Crit Care 11:R68PubMedCrossRef

Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, D’amico G, Goldsmith D, Devarajan P, Bellomo R (2010) Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Med 36:452–461PubMedCrossRef

Bezemer R, Legrand M, Klijn E, Heger M, Post IC, van Gulik TM, Payen D, Ince C (2010) Real-time assessment of renal cortical microvascular perfusion heterogeneities using near-infrared laser speckle imaging. Opt Exp 18:15054–15061CrossRef

Bezemer R, Faber DJ, Almac E, Kalkman J, Legrand M, Heger M, Ince C (2010) Evaluation of multi-exponential curve fitting analysis of oxygen-quenched phosphorescence decay traces for recovering microvascular oxygen tension histograms. Med Biol Eng Comput 48:1233–1242PubMedCrossRef

Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RL, Program to Improve Care in Acute Renal Disease (2009) Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 76:422–427PubMedCrossRef

Boussekey N, Darmon R, Langlois J, Alfandari S, Devos P, Meybeck A, Chiche A, Georges H, Leroy O (2010) Resuscitation with low volume hydroxyethylstarch 130 kDa/0.4 is not associated with acute kidney injury. Crit Care 14:R40PubMedCrossRef

Bredle DL, Samsel RW, Schumacker PT, Cain SM (1989) Critical O2 delivery to skeletal muscle at high and low PO2 in endotoxemic dogs. J Appl Physiol 66:2553–2558PubMed

Cabrales P, Intaglietta M, Tsai AG (2005) Increase plasma viscosity sustains microcirculation after resuscitation from hemorrhagic shock and continuous bleeding. Shock 23:549–555PubMed

Chvojka J, Sykora R, Krouzecky A, Radej J, Varnerova V, Karvunidis T, Hes O, Novak I, Radermacher P, Matejovic M (2008) Renal haemodynamic, microcirculatory, metabolic and histopathological responses to peritonitis-induced septic shock in pigs. Crit Care 12:R164PubMedCrossRef

10.

Di Giantomasso D, Morimatsu H, May CN, Bellomo R (2003) Intrarenal blood flow distribution in hyperdynamic septic shock: effect of norepinephrine. Crit Care Med 31:2509–2513PubMedCrossRef

11.

Dubin A, Pozo MO, Casabella CA, Palizas F Jr, Murias G, Moseinco MC, Kanoore Edul VS, Palizas F, Estenssoro E, Ince C (2009) Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care 13:R92PubMedCrossRef

12.

Dyson A, Bezemer R, Legrand M, Balestra G, Singer M, Ince C (2011) Microvascular and interstitial oxygen tension in the renal cortex and medulla studied in a 4-h rat model of lps-induced endotoxemia. Shock (in press)

13.

Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R (1995) A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med 333:1025–1032PubMedCrossRef

14.

Goldman D, Bateman RM, Ellis CG (2004) Effect of sepsis on skeletal muscle oxygen consumption and tissue oxygenation: interpreting capillary oxygen transport data using a mathematical model. Am J Physiol Heart Circ Physiol 287:H2535–H2544PubMedCrossRef

15.

Hoffmann JN, Vollmar B, Laschke MW, Inthorn D, Schildberg FW, Menger MD (2002) Hydroxyethyl starch (130 kDa), but not crystalloid volume support, improves microcirculation during normotensive endotoxemia. Anesthesiology 97:460–470PubMedCrossRef

16.

Huang YC (2005) Monitoring oxygen delivery in the critically ill. Chest 128:554S–560SPubMedCrossRef

17.

Humer MF, Phang PT, Friesen BP, Allard MF, Goddard CM, Walley KR (1996) Heterogeneity of gut capillary transit times and impaired gut oxygen extraction in endotoxemic pigs. J Appl Physiol 81:895–904PubMed

18.

Inan N, Iltar S, Surer H, Yilmaz G, Alemdaroglu KB, Yazar MA, Basar H (2009) Effect of hydroxyethyl starch 130/0.4 on ischaemia/reperfusion in rabbit skeletal muscle. Eur J Anaesthesiol 26:160–165PubMedCrossRef

19.

Ince C, Sinaasappel M (1999) Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med 27:1369–1377PubMedCrossRef

20.

Jang HR, Ko GJ, Wasowska BA, Rabb H (2009) The interaction between ischemia-reperfusion and immune responses in the kidney. J Mol Med 87:859–864PubMedCrossRef

21.

Jhanji S, Stirling S, Patel N, Hinds CJ, Pearse RM (2009) The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock. Crit Care Med 37:1961–1966PubMedCrossRef

22.

Johannes T, Mik EG, Klingel K, Dieterich HJ, Unertl KE, Ince C (2008) Low-dose dexamethasone supplemented fluid resuscitation reverses endotoxin-induced acute renal failure and prevents cortical microvascular hypoxia. Shock 31:521–528CrossRef

23.

Johannes T, Mik EG, Ince C (2009) Nonresuscitated endotoxemia induces microcirculatory hypoxic areas in the renal cortex in the rat. Shock 31:97–103PubMedCrossRef

24.

Kinsey GR, Li L, Okusa MD (2008) Inflammation in acute kidney injury. Nephron Exp Nephrol 109:e102–e107PubMedCrossRef

25.

Langenberg C, Bellomo R, May C, Wan L, Egi M, Morgera S (2005) Renal blood flow in sepsis. Crit Care 9:R363–R374PubMedCrossRef

26.

Langenberg C, Wan L, Egi M, May CN, Bellomo R (2007) Renal blood flow and function during recovery from experimental septic acute kidney injury. Intensive Care Med 33:1614–1618PubMedCrossRef

27.

Le Dorze M, Legrand M, Payen D, Ince C (2009) The role of the microcirculation in acute kidney injury. Curr Opin Crit Care 15:503–508PubMedCrossRef

28.

Legrand M, Almac E, Mik EG, Johannes T, Kandil A, Bezemer R, Payen D, Ince C (2009) L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats. Am J Physiol Renal Physiol 296:F1109–F1117PubMedCrossRef

29.

Lo LW, Vinogradov SA, Koch CJ, Wilson DF (1997) A new, water soluble, phosphor for oxygen measurements in vivo. Adv Exp Med Biol 428:651–656PubMedCrossRef

30.

Mårtensson J, Bell M, Oldner A, Xu S, Venge P, Martling CR (2010) Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Med 36:1333–1340PubMedCrossRef

31.

Nelson DP, Samsel RW, Wood LD, Schumacker PT (1988) Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia. J Appl Physiol 64:2410–2419PubMed

32.

Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL, Sepsis Occurrence in Acutely Ill Patients (SOAP) Investigators (2008) A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 12:R74PubMedCrossRef

33.

Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative Group (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377PubMedCrossRef

34.

Saotome T, Ishikawa K, May CN, Birchall IE, Bellomo R (2010) The impact of experimental hypoperfusion on subsequent kidney function. Intensive Care Med 36:533–540

35.

Schumacker PT, Samsel RW (1989) Analysis of oxygen delivery and uptake relationships in the Krogh tissue model. J Appl Physiol 67:1234–1244PubMed

36.

Tyml K, Li F, Wilson JX (2008) Septic impairment of capillary blood flow requires nicotinamide adenine dinucleotide phosphate oxidase but not nitric oxide synthase and is rapidly reversed by ascorbate through an endothelial nitric oxide synthase-dependent mechanism. Crit Care Med 36:2355–2362PubMedCrossRef

37.

Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C (2005) Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 294:813–818PubMedCrossRef

38.

Vinogradov SA, Grosul P, Rozhkov V, Dunphy I, Shuman L, Dugan BW, Evans S, Wilson DF (2003) Oxygen distributions in tissue measured by phosphorescence quenching. Adv Exp Med Biol 510:181–185PubMed

39.

Walley KR (1996) Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues: theory. J Appl Physiol 81:885–894PubMed

Title: The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats
Authors: Matthieu Legrand
Rick Bezemer
Asli Kandil
Cihan Demirci
Didier Payen
Can Ince
Publication date: 01-09-2011
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 9/2011
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-011-2267-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 9/2011

The use of the Boussignac CPAP device during cardiogenic pulmonary edema (CPE): why add air to the oxygen gas source?

The number of failing organs predicts non-invasive ventilation failure in children with ALI/ARDS

Arginine–vasopressin and corticosteroids in septic shock: engaged but not yet married!

The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks

A UK approach to urgent endotracheal intubation

Early steroid therapy for patients with H1N1 influenza A virus infection