IN-VIVO STUDY OF HALOTHANE HEPATOTOXICITY IN THE RAT USING MAGNETIC-RESONANCE-IMAGING AND P-31 SPECTROSCOPY

Using magnetic resonance imaging (MRI) and spectroscopy (MRS), in vivo halothane hepatotoxicity was assessed in male Wistar rats. With 1.5% halothane in 100 or 20% O-2, an edematous region, characterized by inc reased intensity on T-2 weighted images and an increase in regional ti ssue water content (rho(water)), was seen proximal to the hepatic port al vein in the liver. Both spin-lattice relaxation (T-1) and spin-spin relaxation (T-2) increased in this region, relative to distal regions of the liver. Similarly, a high signal intensity on proton density we ighted images was observed in this area. As halothane anaesthesia prog ressed, a decrease in the adenosine triphosphate-inorganic phosphate r atio (ATP/P-i) and an increase in the phosphomonoester-phosphodiester (PME/PDE) ratio was detected in the liver. In addition, intracellular pH decreased and intracellular free magnesium concentration [Mg2+] inc reased with time of exposure. Excessive vacuolation, ribosomal disappe arance from rough endoplasmic reticulum, mitochondrial swelling and fr agmentation of smooth endoplasmic reticulum were observed by transmiss ion electron microscopy (TEM) in samples from the edematous region of the liver. (C) 1997 Elsevier Science B.V.