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Urinary trypsin inhibitor ameliorates renal tissue oxygenation after ischemic reperfusion in rats

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Abstract

Purpose

In order to determine the mechanism of the protective effect of a urinary trypsin inhibitor (UTI) on renal ischemic reperfusion injury, we measured the tissue oxygen partial pressure (\( p_{O_2 } \)) in both the renal cortex and medulla in rats, using electron paramagnetic resonance (EPR) oximetry.

Methods

We allocated the rats to three groups: normal saline (NS) group, a UTI 50 000 U·kg−1 (LD) group, and a UTI 150 000 U·kg−1 (HD) group, with the normal saline and UTI being administered 30 min before ischemia. Renal ischemia was achieved by inflating the balloon of a vascular occluder that had been placed around the abdominal aorta just above the bifurcation of the renal artery. Cortical and medullary \( p_{O_2 } \) were measured every 10 min during ischemia (30 min) and reperfusion (60 min) by EPR oximetry; also, systemic cardiopulmonary parameters were measured.

Results

The \( p_{O_2 } \) in the cortex and medulla decreased to less than 2 mmHg during ischemia in all groups. At 60 min after reperfusion, the \( p_{O_2 } \) values in the NS group were not fully restored, whereas those in the LD and HD groups were completely restored to the pre-ischemic values. There were no significant differences between the HD and LD groups. There were no differences between any groups in cardiopulmonary parameters.

Conclusion

Because UTI improved renal oxygenation after reperfusion without changing cardiopulmonary parameters, the pharmacological properties of UTI, such as its renal protection and anti-shock activity, may be explained in part, by this improvement in tissue oxygenation.

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References

  1. Cornard MF, Craeford RS, Davison JK, Cambria RPC. Thoracoabdominal aneurysm repair: a 20-year perspective. Ann Thorac Surg. 2007;83:S856–S861.

    Article  Google Scholar 

  2. Bonventre JV, Weinberg JM. Recent advances in the pathophysiology of ischemic acute renal failure. J Am Soc Nephrol. 2003;14:2199–2210.

    Article  PubMed  Google Scholar 

  3. Nelimarkka O. Renal oxygen and lactate metabolism in hemorrhagic shock: an experimental study. Acta Chir Scand Suppl. 1984;518:1–44.

    PubMed  CAS  Google Scholar 

  4. Binns OA, DeLima NF, Buchanan SA, Mauney MC, Cope JT, Thies SD, Shockey KS, Tribble CG, Kron IL. Neutrophil endopeptidase inhibitor improves pulmonary function during reperfusion after 18-hour preservation. J Thorac Cardiovasc Surg. 1996;112:607–613.

    Article  PubMed  CAS  Google Scholar 

  5. Hirose J, Ozawa T, Miura T, Isaji M, Nagao Y, Yamashiro K, Nii A, Kato K, Uemura A. Human neutrophil elastase degrades inter-α-trypsin inhibitor to liberate urinary trypsin inhibitor related proteins. Biol Pharm Bull. 1998;21:651–656.

    PubMed  CAS  Google Scholar 

  6. Masuda T, Sato K, Noda C, Ikeda K, Matsunaga A, Ogura M, Shimizu K, Nagasawa H, Matsuyama N, Izumi T. Protective effect of urinary trypsin inhibitor on myocardial mitochondria during hemorrhagic shock and reperfusion. Crit Care Med. 2003;31: 1987–1992.

    Article  PubMed  CAS  Google Scholar 

  7. Komori M, Takada K, Tomizawa Y, Uezono S, Ozaki M. Urinary trypsin inhibitor improves peripheral microcirculation and bronchospasm associated with systemic anaphylaxis in rabbits in vivo. Shock. 2003;20:189–194.

    Article  PubMed  CAS  Google Scholar 

  8. Chen CC, Liu ZM, Wang HH, He W, Wang Y, Wu WD. Effects of ulinastatin on renal ischemia-reperfusion injury in rats. Acta Pharmacol Sin. 2004;25:1334–1340.

    PubMed  CAS  Google Scholar 

  9. Nakahama H, Obata K, Sugita M. Ulinastatin ameliorates acute ischemic renal injury in rats. Ren Fail. 1996;18:893–898.

    Article  PubMed  CAS  Google Scholar 

  10. Taie S, Yokono S, Ueki M, Ogli K. Effects of ulinastatin (urinary trypsin inhibitor) on ATP, intracellular pH, and intracellular sodium transients during ischemia and reperfusion in the rat kidney in vivo. J Anesth. 2001;15:33–38.

    Article  PubMed  CAS  Google Scholar 

  11. Swartz HM, Clarkson RB. The measurement of oxygen in vivo using EPR techniques. Phys Med Biol. 1998;43:1957–1975.

    Article  PubMed  CAS  Google Scholar 

  12. Hou H, Grinberg OY, Williams B, Grinberg S, Yu H, Alvarenga DL, Wallach H, Buckey J, Swartz HM. The effect of oxygen therapy on brain damage and cerebral pO2 in transient focal cerebral ischemia in the rat. Physiol Meas. 2007;28:963–976.

    Article  PubMed  Google Scholar 

  13. Hou H, Grinberg OY, Taie S, Leichtweis S, Miyake M, Grinberg S, Xie H, Csete M, Swartz HM. Electron paramagnetic resonance assessment of brain tissue oxygen tension in anesthetized rats. Anesth Analg. 2003;96:1467–1472.

    Article  PubMed  Google Scholar 

  14. Nakajima K, Goto Y. Differentiation of the anti-shock effect of ulinastatin from steroid hormone, by the continuous observation of microcirculation dynamics. Circ Shock. 1992;36:284–289.

    PubMed  CAS  Google Scholar 

  15. Kawamura T, Inada K, Akasaka N, Wakusawa R. Ulinastatin reduces elevation of cytocines and soluble adhesion molecules during cardiac surgery. Can J Anaesth. 1996;43:456–460.

    Article  PubMed  CAS  Google Scholar 

  16. Aosasa S, Ono S, Seki S, Takayama E, Tadakuma T, Hiraide H, Mochizuki H. Inhibitory effect of protease inhibitor on endothelial cell activation. J Surg Res. 1998;80:182–187.

    Article  PubMed  CAS  Google Scholar 

  17. Inoue K, Takano H, Shimada A, Yanagisawa R, Sakurai M, Yoshino S, Sato H, Yoshikawa T. Urinary trypsin inhibitor protects against systemic inflammation induced by lipopolysaccharide. Mol Pharmacol. 2005;67:673–680.

    Article  PubMed  CAS  Google Scholar 

  18. Yano T, Anraku S, Nakayama R, Ushijima K. Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemiareperfusion injury in rats. Anesthesiology. 2003;98:465–473.

    Article  PubMed  CAS  Google Scholar 

  19. Ueki M, Taie S, Chujo K, Asaga T, Iwanaga Y, Ono J, Maekawa N. Urinary trypsin inhibitor reduces inflammatory response in kidney induced by lipopolysaccharide. J Biosci Bioeng. 2007;104: 315–320.

    Article  PubMed  CAS  Google Scholar 

  20. Brezis M, Rosen S. Hypoxia of the renal medulla—its implications for disease. N Engl J Med. 1995;332:647–655.

    Article  PubMed  CAS  Google Scholar 

  21. Juillard L, Lerman LO, Kruger DG, Haas JA, Rucker BC, Polzin JA, Riederer SJ, Romero JC. Blood oxygen leveldependent measurement of acute intra-renal ischemia. Kidney Int. 2004;65:944–950.

    Article  PubMed  Google Scholar 

  22. Whitehouse T, Stotz M, Taylor V, Stidwill R, Singer M. Tissue oxygen and hemodynamics in renal medulla, cortex, and corticomedullary junction during hemorrhage-reperfusion. Am J Physiol Renal Physiol. 2006;291:F647–F653.

    Article  PubMed  CAS  Google Scholar 

  23. Endo S, Inada K, Taki K, Hoshi S, Yoshida M. Inhibitory effects of ulinastatin on the production of cytokines: implications for the prevention of septicemic shock. Clin Ther. 1990;12:323–326.

    PubMed  CAS  Google Scholar 

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Taie, S., Ueki, M., Chujo, K. et al. Urinary trypsin inhibitor ameliorates renal tissue oxygenation after ischemic reperfusion in rats. J Anesth 22, 149–154 (2008). https://doi.org/10.1007/s00540-007-0602-2

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  • DOI: https://doi.org/10.1007/s00540-007-0602-2

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