31P nuclear magnetic resonance in vivo spectroscopy of the metabolic changes induced in the awake rat brain during KCN intoxication and its reversal by hydroxocobalamine.

Abstract

Radiofrequency surface coils were chronically implanted in rats, which were subsequently subjected to 31P nuclear magnetic resonance (NMR) investigations at 4.7 T. The implanted coil allowed study of the animals without need for anesthesia, which is a prerequisite for studies of normal brain metabolism. The animals may be kept in the NMR probe for several hours. During subsequent experiments, they may be placed in the same position, therefore allowing follow-up studies for periods as long as 2 months. This method has been used in the study of sublethal KCN intoxication. KCN, a cytochrome c oxidase inhibitor, induces a blockade of cell respiratory processes, which is reflected, in a dose-dependent manner, by a decrease in phosphocreatine content and pH and an increase in inorganic phosphate content, whereas ATP levels remain constant until high doses of KCN (6 mg/kg i.p.) are reached. 31P NMR allows the time course of these metabolic changes to be followed. For high KCN doses, a new peak, termed X, is observed, which is interpreted as being due to a pool of inorganic phosphate at very low pH (5.65), corresponding to a subset of cells that did not survive KCN injury. Hydroxocobalamine, a specific antidote of KCN, suppresses the metabolic changes due to 6 mg/kg of KCN.