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 P/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 pH_i to baseline during the recovery period. In Gallopamil-treated cats, higher levels of lactate were necessary to cause a similar decrease in pH_i 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. © 1987 Academic Press, Inc.