F19 NMR spectroscopy will be used to directly and noninvasively monitor the distribution of four fluorinated anesthetic agents (halothane, methoxyflurane, isofluraneand enflurane) in rabbit brain. The compounds selected vary in their potencies as anesthetic agents, in their solubilities in various tissues, and in the degree of their bio-transformation.

The F19 signals derived from the anesthetic molecule itself will be used to detect its presence and to assess the enviroment(s) in which this molecule resides within the brain tissue. Distribution of anesthetic within brain tissue will be outlinted with one-dimensional mapping experiments which retain the chemical shift information, and followed with 2-D F19 imaging to identify the specific brain regions involved.

The time-courses of the anesthetic uptake and elimination from the brain and their dependency on the administered dose will be studied. To unequivically identi the origin of the observed F19 signals, the in vivo results will be supplemented by studies of brain samples excised from animals sacrificed at selected intervals during and after anesthesia is terminated. The fluorine-containing compounds will then be isolated from the tissue and identified using chromatography, NMR spectroscopy, and GC Mass spectrometry. Changes in the muscle membranes and in the muscle energy metabolism induced by anesthetics will be examined both in vivo and in vitro. Results from these studies which will include F19, C13, and 31p NMR measurements will be used to infer how anesthetics can bring about malilgnant hyperthermia. The binding of anesthetics to red blood cells will be examined in more detail by monitoring F19 and C13 NMR signals of the anesthetic molecules when bound to the cell. Dynamics of the binding process will be examined with T1 and T2 relaxation time measurements.

R01GM029520

1981-09-01

1988-06-30