³¹P and ¹H NMR spectroscopy to study the effects of Gallopamil on brain ischemia

Abstract

Studies were performed on 16 cats to evaluate the potential protective effects of Gallopamil on brain ischemia. Brain energy state was determined by 31P NMR and lactate concentration was determined by 1H NMR. Double-tuned surface coils (tuned to 35.8 and 88.4, respectively) were placed on the head after skin and muscle were removed from the calvarium. A 2.1-T, 25-cm-bore Oxford magnet interfaced to a Phosphoenergetics 250-80 spectrometer was used. The cats were bled to 50 mm Hg for 10 min with subsequent application of bilateral carotid occlusion for 10 min to produce ischemia. In all animals, brain energy state as measured by Pi/PCr and lactate concentrations were determined over 5-min intervals (before, during, and after the onset of ischemia). While Gallopamil did not prevent decreases in brain energy state or attenuate the rise in lactate concentration seen during ischemia, brain from animals treated with Gallopamil had a more rapid return of pHi to baseline during the recovery period. In Gallopamil-treated cats, higher levels of lactate were necessary to cause a similar decrease in pHi when compared to controls. The rate of lactate recovery to baseline levels was similar in both groups (control = -0.38 +/- 0.14 mM/min; Gallopamil = -0.44 +/- 0.32 mM/min). In conclusion, Gallopamil appears to lessen the acidosis caused by cerebral ischemia. In addition, we have demonstrated that multinuclear NMR spectroscopy is a powerful tool to study the effects of drugs on cerebral metabolism.

Effects of dextromethorphan on rat brain during ischemia and reperfusion assessed by magnetic resonance spectroscopy.

“…manded for the extrusion of intracellular Ca 2+ is reduced by blockade of these two routes of Ca 2+ influx into the cells. 26 An intracellular Ca 2+ overload adversely affects mitochondrial function by uncoupling oxidative phosphorylation. 3 By blocking the Ca 2+ influx, NMDA antagonists might preserve mitochondrial oxidation and allow oxidative metabolism to continue in cells not totally deprived of oxygen, leading to a diminished production of Lac.…”

Nonedited 1H NMR lactate/n‐acetyl aspartate ratios and the in vivo determination of lactate concentration in brain

“…This interest in lactate is largely due to the fact that this metabolite has been implicated as a primary determinant of irreversible tissue damage following central nervous system (CNS) injury (2). In light of the purported threshold levels that must be reached for lactate to have deleterious effects (2), many studies of brain metabolism following experimental CNS injury have attempted to quantitate brain lactate concentration in vivo (3)(4)(5).…”