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Effect of graded hypoxia on the rat hepatic tissue oxygenation and energy metabolism monitored by near-infrared and ³¹P nuclear magnetic resonance spectroscopy

Hepatic Haemodynamic Laboratory, University Department of Surgery, Royal Free and University College Medical School, University College London, The Royal Free Hospital, London; and
^* Department of Medical Physics and Bioengineering, University College London, London, UK

¹Correspondence: University Department of Surgery, Royal Free and University College Medical School, University College London, The Royal Free Hospital, Pond St., London, NW3 2QG, UK. E-mail: a.seifalian{at}rfc.ucl.ac.uk

Alteration in hepatic cellular adenosine triphosphate (ATP) levels has been shown to be a sensitive index for hypoxic damage. Hepatic ATP metabolism can be monitored by ³¹P nuclear magnetic resonance (NMR). Near-infrared spectroscopy (NIRS) can measure tissue oxyhemoglobin (HbO₂), deoxyhemoglobin (Hb), and cytochrome oxidase (Cyt Ox), which reflect ATP production. In this study, hepatic oxygenation parameters have been correlated with ATP metabolism under graded hypoxia. Sprague-Dawley rats underwent laparotomy for liver exposure. NIRS probes and an NMR coil were placed on the liver and the animal was positioned in the NMR magnet. Graded hypoxia was achieved by a stepwise reduction of the fraction of inspired oxygen (FiO₂) from 15 to 4%. Recovery between the hypoxic periods was achieved using 30% oxygen. Hepatic tissue oxygenation parameters were measured continuously by NIRS; ³¹P-NMR spectra obtained at 1 min intervals from energy metabolites and intracellular pH were calculated. All the hypoxic grades produced an immediate reduction in HbO₂ with a simultaneous increase in Hb. Cyt Ox was reduced significantly only with FiO₂ of 10%. ³¹P-NMR spectra showed a significant decrease in cellular ß nucleoside triphosphate (ß-NTP) only with FiO₂ of 10%. Significant correlation was seen between ß-NTP and HbO₂ (r=0.85), Hb (r=-0.74), and Cyt Ox (r=0.81). Cyt Ox was reduced with intracellular hypoxia and correlated temporally with the reduction of cellular ß-NTP, and therefore could be used as an index for the changes in ß-NTP with hypoxia.—Seifalian, A. M., El-Desoky, E.-H., Delpy, D. T., Davidson, B. R. Effect of graded hypoxia on the rat hepatic tissue oxygenation and energy metabolism monitored by near-infrared and ³¹P nuclear magnetic resonance spectroscopy.

Key Words: NIMR • liver hypoxia • ß nucleoside triphosphate

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