In vivo Li-7 NMR studies on shift reagent infused rats

Lithium (Li+) is used widely in the treatment and prophylaxis of bipolar di sorder. The mechanism of action remains unknown. There have been many studi es of intracellular lithium and its fluxes in the human red blood cells (RB Cs) with a view towards understanding the maintenance of Li+ levels inside the cells and the mechanism of Li+ therapeutic action. Such information is valuable for excitable cells such as neurons, the likely site of therapeuti c effects, and muscle, the site of common side effects. As intracellular Li + may be responsible for both muscle irritability and pathological changes in the electrocardiogram, there is a need to discriminate intra-, and extra cellular Li+ components. To date there is no other human cell for which eit her intracellular Li+ levels or its fluxes have been measured. The muscle t issue with a large concentration of lithium should serve as a suitable mode l for infusion studies in an in vivo set up. In addition to the intrinsic i mportance of muscle as a site of side effects of Li+ therapy, muscle as an excitable cell may be a better model for the brain than the RBCs. In this s tudy, using the shift reagent thulim(III) 1,4,7,10-tetraazacyclododecane-1, 4,7,10-tetrakis(methylene phosphonate) (TmDOTP5-), two distinct resonances were observed in the head tissue of rats. Based on earlier results that the brain lithium signal is significantly small compared to the rest of the ti ssue in the head, the unshifted resonance was attributed as largely due to intracellular Li+; the shifted resonance was attributed to Li+ present outs ide the cells (plasma or interstitial). Our study demonstrates that TmDOTP5 - infused in animals treated with lithium can discriminate the intra- and e xtracellular Li+ in tissue in vivo.