A rat model of acute kidney injury through systemic hypoperfusion evaluated by micro-US, color and PW-Doppler

  • Francesca IacobellisEmail author
  • Teresa Segreto
  • Daniela Berritto
  • Francesca Nettuno
  • Santolo Cozzolino
  • Daniele Di Napoli
  • Marco Montella
  • Raffaele Natella
  • Salvatore Cappabianca
  • Luca Brunese
  • Roberto Grassi



To create an animal model of acute renal ischemia induced by systemic hypoperfusion, controllable and reproducible to study, in real time, hemorrhagic shock changes with micro-imaging.

Animals and methods

Hemorrhagic shock was induced in rats activating a syringe pump setup to remove 1 mL/min of blood, through the femoral artery catheter. The withdrawal was continued until the mean arterial pressure (MAP) dropped to 25–30 mmHg. For the next 60 min, the MAP was maintained at a constant pressure value, by automatic pump infusion and withdrawal. Micro-ultrasound imaging was performed using the Vevo 2100 system with the MS250 transducer (13–24 MHz). Renal size, morphology and echogenicity were evaluated in B-mode. Renal blood flow was evaluated using color and PW-Doppler.


After 1 h of ischemia, B-mode images documented slight changes in kidney echogenicity. Color and PW-Doppler analysis showed a reduction in renal blood flow in kidneys during the hypoperfusion with a progressive and significant change from baseline values of resistive index (RI). At the histological evaluation, 60 min of hypoperfusion resulted in ischemic changes in the kidneys.


The results of this experimental study encourage the use of the described model to study acute renal ischemia trough severe hypoperfusion. The histological data confirmed that the model was able to produce injury in renal parenchyma. It can be used to assess acute ischemic damage not only in the kidney but also in other organs by using all available dedicated small animals imaging techniques.


Animal model Hypoperfusion Kidney injury Hemorrhagic shock Renal blood flow 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed.


  1. 1.
    Legrand M, Mik EG, Johannes T, Payen D, Ince C (2008) Renal hypoxia and dysoxia after reperfusion of the ischemic kidney. Mol Med 14:502–516CrossRefGoogle Scholar
  2. 2.
    Zhao ZG, Zhu HX, Zhang LM, Zhang YP, Niu CY (2014) Mesenteric lymph drainage alleviates acute kidney injury induced by hemorrhagic shock without resuscitation. Sci World J 5:78. CrossRefGoogle Scholar
  3. 3.
    Solez K, Morel-Maroger L, Sraer JD (1979) The morphology of “acute tubular necrosis” in man: analysis of 57 renal biopsies and a comparison with the glycerol model. Medicine (Baltimore) 58:362–376CrossRefGoogle Scholar
  4. 4.
    Boesen EI, Crislip GR, Sullivan JC (2012) Use of ultrasound to assess renal reperfusion and P-selectin expression following unilateral renal ischemia. Am J Physiol Renal Physiol 303:F1333–F1340CrossRefGoogle Scholar
  5. 5.
    Iacobellis F, Berritto D, Belfiore MP, Di Lanno I, Maiorino M, Saba L, Grassi R (2014) Meaning of free intraperitoneal fluid in small-bowel obstruction: preliminary results using high-frequency microsonography in a rat model. J Ultrasound Med 33:887–893CrossRefGoogle Scholar
  6. 6.
    Belfiore MP, Berritto D, Iacobellis F, Rossi C, Nigro G, Rotundo IL, Cozzolino S, Cappabianca S, Rotondo A, Grassi R (2011) A longitudinal study on BIO14.6 hamsters with dilated cardiomyopathy: micro-echocardiographic evaluation. Cardiovasc Ultrasound 9:39CrossRefGoogle Scholar
  7. 7.
    Arendshorst WJ, Finn WF, Gottschalk CW (1975) Pathogenesis of acute renal failure following temporary renal ischemia in the rat. Circ Res 37:558–568CrossRefGoogle Scholar
  8. 8.
    Hueper K, Gutberlet M, Rong S, Hartung D, Mengel M, Xia Lu, Haller H, Wacker F, Meier M, Gueler F (2014) Acute kidney injury: arterial spin labeling to monitor renal perfusion impairment in mice—comparison with histopathologic results and renal function. Radiology 270:117–124CrossRefGoogle Scholar
  9. 9.
    Park BK, Kim SH, Moon MH, Jung SI (2005) Imaging features of gray-scale and contrast-enhanced color Doppler US for the differentiation of transient renal arterial ischemia and arterial infarction. Korean J Radiol 6:179–184CrossRefGoogle Scholar
  10. 10.
    Sato H, Tanaka T, Kita T, Tanaka N (2010) A quantitative study of lung dysfunction following hemorrhagic shock in rats. Int J Exp Pathol 91:267–275CrossRefGoogle Scholar
  11. 11.
    Halvorsen L, Gunther RA, Dubick MA, Holcroft JW (1991) Dose–response characteristics of hypertonic saline–dextran solutions. J Trauma 31:785–793CrossRefGoogle Scholar
  12. 12.
    Eser O, Kalkan E, Cosar M, Buyukbas S, Avunduk MC, Aslan A, Kocabas V (2007) The effect of aprotinin on brain ischemic–reperfusion injury after hemorrhagic shock in rats: an experimental study. J Trauma 63:373–378CrossRefGoogle Scholar
  13. 13.
    Stein HJ, Hinder RA, Oosthuizen MMJ (1990) Gastric mucosal injury caused by hemorrhagic shock and reperfusion: protective role of the antioxidant glutathione. Surgery 108:467–473PubMedGoogle Scholar
  14. 14.
    Greiffenstein P, Mathis KW, Stouwe CV, Molina PE (2007) Alcohol binge before trauma–hemorrhage impairs integrity of host defense mechanisms during recovery. Alcohol Clin Exp Res 31:704–715PubMedGoogle Scholar
  15. 15.
    Rönn T, Lendemans S, de Groot H, Petrat F (2011) A new model of severe hemorrhagic shock in rats. Comp Med 61:419–426PubMedPubMedCentralGoogle Scholar
  16. 16.
    Rohrig R, Wegewitz C, Lendemans S, Petrat F, de Groot H (2014) Superiority of acetate compared with lactate in a rodent model of severe hemorrhagic shock. J Surg Res 186:338–345CrossRefGoogle Scholar
  17. 17.
    Grassi R, Cavaliere C, Cozzolino S, Mansi L, Cirillo S, Tedeschi G, Franchi R, Russo P, Cornacchia S, Rotondo A (2009) Small animal imaging facility: new perspectives for the radiologist. Radiol Med 114:152–167CrossRefGoogle Scholar
  18. 18.
    Grassi R, Lagalla R, Rotondo A (2008) Genomics, proteomics, MEMS and SAIF: which role for diagnostic imaging? Radiol Med 113:775–778CrossRefGoogle Scholar
  19. 19.
    Platt JF (1992) Duplex Doppler evaluation of native kidney dysfunction: obstructive and nonobstructive disease. AJR Am J Roentgenol 158:1035–1042CrossRefGoogle Scholar
  20. 20.
    Gao J, Hentel K, Zhu Q, Ma T, Shih G, Mennitt K, Min R (2011) Doppler angle correction in the measurement of intrarenal parameters. Int J Nephrol Renovasc Dis 4:49–55CrossRefGoogle Scholar
  21. 21.
    Rivers BJ, Walter PA, O'Brien TD, Polzin DJ (1996) Duplex Doppler estimation of Pourcelot resistive index in arcuate arteries of sedated normal cats. J Vet Intern Med 10(1):28–33CrossRefGoogle Scholar
  22. 22.
    Zhong Z, Enomoto N, Connor HD, Moss N, Mason RP, Thurman RG (1999) Glycine improves survival after hemorrhagic shock in the rat. Shock 12:54–62CrossRefGoogle Scholar
  23. 23.
    Russell DH, Barreto JC, Klemm K, Miller TA (1995) Hemorrhagic shock increases gut macromolecular permeability in the rat. Shock 4:50–55CrossRefGoogle Scholar
  24. 24.
    Pohlmann A, Hentschel J, Fechner M, Hoff U, Bubalo G, Arakelyan K, Cantow K, Seeliger E, Flemming B, Waiczies H, Waiczies S, Schunck WH, Dragun D, Niendorf T (2013) High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury. PLoS ONE 8:e57411CrossRefGoogle Scholar
  25. 25.
    Darmon M, Schnell D, Zeni F (2010) Doppler-based renal resistive index: a comprehensive review. In: Vincent JL (ed) Yearbook of intensive care and emergency medicine, vol 2010. Springer, BerlinGoogle Scholar
  26. 26.
    Berritto D, Iacobellis F, Belfiore MP, Rossi C, Saba L, Grassi R (2014) Early MRI findings of small bowel obstruction: an experimental study in rats. Radiol Med 119:377–383CrossRefGoogle Scholar
  27. 27.
    Somma F, Berritto D, Iacobellis F, Landi N, Cavaliere C, Corona M, Russo S, Di Mizio R, Rotondo A, Grassi R (2013) 7T μMRI of mesenteric venous ischemia in a rat model: timing of the appearance of findings. Magn Reson Imaging 31(3):408–413CrossRefGoogle Scholar
  28. 28.
    Berritto D, Iacobellis F, Somma F, Corona M, Faggian A, Iacomino A, Feragalli B, Saba L, La Porta M, Grassi R (2013) 7T mMR in the assessment of acute arterial mesenteric ischemia in a rat model. J Biol Regul Homeost Agents 27:771–779PubMedGoogle Scholar

Copyright information

© Italian Society of Medical Radiology 2018

Authors and Affiliations

  • Francesca Iacobellis
    • 1
    • 2
    Email author
  • Teresa Segreto
    • 1
  • Daniela Berritto
    • 1
  • Francesca Nettuno
    • 1
  • Santolo Cozzolino
    • 2
  • Daniele Di Napoli
    • 2
  • Marco Montella
    • 3
  • Raffaele Natella
    • 1
  • Salvatore Cappabianca
    • 1
  • Luca Brunese
    • 4
  • Roberto Grassi
    • 1
  1. 1.Department of RadiologyUniversity of Campania “L. Vanvitelli”NaplesItaly
  2. 2.Biotechnology’s Center“A. Cardarelli” HospitalNaplesItaly
  3. 3.Division of Pathology, Department of Public, Clinic and Preventive MedicineSecond University of NaplesNaplesItaly
  4. 4.Department of RadiologyUniversity of MoliseCampobassoItaly

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