PhD

dissertationIn vivo nuclear magnetic resonance (NMR) was employed to study cerebral energy metabolism under hypoxia, cerebral blood flow (CBF), and isoflurane elimination kinetics as a function of age in rat brain. Three nuclei were involved: 31P for energy metabolism, 2H for monitoring D2O clearance to calculate cerebral blood flow and 19F for studying isoflurane kinetics and T1 and T2 relaxation times. Energy metabolites were monitored by 31P NMR in both horizontal and vertical magnets on rat brain experiencing the same level of hypoxia. The changes in PCr, Pi and pHi in the vertical position toward the end of hypoxia were significantly larger and the recovery in the horizontal animals was more complete. These results demonstrated quantitatively that the stress of the vertical alignment on the supine animal is superimposed upon the stress of hypoxia in the vertical experiment. Cerebral blood flow measurement by 2H NMR using the deuterium oxide internal carotid artery injection method was established. Values of global CBF were in the same range as those reported using other methods and were found to be linearly correlated with arterial CO2 tension (PaCO2). Measurements in a single animal can be repeated several times to obtain reproducible values under the same physiological condition or different values under altered physiological conditions. Isoflurane elimination from rat brain as a function of age was studied by 19F NMR. The results showed that the elimination from both young and old rat brain was biphasic whereas the half lives (t1/2) of both the fast and slow components for the old were 15% slower than their counterparts of the young rat group. Similar age attenuation was also found from arterial blood elimination to the same extent with a monophasic process as measured by gas chromatography. Longitudinal relaxation (T1) measurements showed monoexponential recovery and no age difference. T1 recovery in dipalmitoylphosphatidylcholine (DPPC) vesicles was longer indicating less restricted motion compared with that in the intact brain. Transverse relaxation recovery in DPPC vesicles was also monoexponential. This dissertation has demonstrated that in vivo NMR is a useful noninvasive tool in the studying of energy metabolism and pharmacokinetics of fluorinated drugs in rodent brain