To the Editor:
I was deeply impressed by the recently published work “Deep Isoflurane Anesthesia Is Associated with Alterations in Ion Homeostasis and Specific Na+/K+-ATPase Impairment in the Rat Brain” by Reiffurth et al.
A long time ago, I was introduced by chance to Professor Gunnar Ronquist at Uppsala University, Sweden, and was introduced to his method of analyzing adenylate kinase in cerebrospinal fluid (CSF). This enzyme, which has a central role in energy metabolism—catalyzing the dismutation reaction 2 ADP ↔ AMP + ATP—is strictly intracellular. Its physicochemical properties of low molecular weight (about 22,000 Da) and high turnover rate in CSF explain its value as a damage marker. If found extracellularly, e.g., in CSF, it indicates disruption of cellular integrity. So, adenylate kinase leaked into the CSF signals neuronal damage. By then, CSF adenylate kinase had already been used to detect brain damage associated with brain tumors in schizophrenia in neurologic diseases after open-heart surgery in meningoencephalitis after circulatory arrest and in hypoxic newborns. I thought, it would be interesting to use this analysis to show that deep isoflurane anesthesia for induced hypotension for orthognathic surgery carries no risk to the brain.
Unfortunately, the hypothesis was wrong. In a first pilot study, “nine out of ten patients showed a marked increase in CSF adenylate kinase postoperatively compared with preoperative values.” Our first guess was that hypotension explained the result. However, in a subsequent study, in which patients were randomly assigned to hypo- or normotension, we could not confirm the hypothesis. At this stage, we speculated on the role of ion pumps. A PhD student worked hard for several months trying to set up a mouse model to investigate this aspect, but he unfortunately failed. I guess the time was not right. Happily, technologic progress has come so far that Clemens Reiffurth et al. now have detailed insights into ion flows during isoflurane anesthesia.1
I look forward to following the work of this group and congratulate them on their success so far.