Coupling of Local Cerebral Blood Flow to Local Cerebral Glucose Utilization during Isoflurane and Sevoflurane Anesthesia 

Archer and Pappius correctly state that “blood flow–metabolism coupling conventionally refers to changes in blood flow within a brain region in response to changes in metabolism in that region.” This is certainly a definition that is generally accepted. However, it is rather common to use the term coupling also in a broader sense to describe the long-term adjustment of local cerebral blood flow to the local metabolic rate for each brain structure. 1 

Archer and Pappius have applied statistical analysis to local cerebral blood flow (LCBF):local cerebral glucose utilization (LCGU) ratios and cited the method of McColloch et al.  2In the originally submitted manuscript, we included the statistical analysis of McCulloch et al.  2,3and we applied it to all data. However, during the review process the criticism was raised that LCGU and LCBF values obtained from multiple brain structures in a single animal are not independent from each other and cannot be analyzed by a test that assumes they are. In addition, it was objected that comparison includes, in addition to 1 MAC versus  2 MAC versus  sevoflurane versus  isoflurane, also any structure examined. We became convinced by these objections and therefore waived any kind of statistical analysis of flow–metabolism “coupling” data.

Archer and Pappius propose a statistical analysis for specific brain regions and make specific statements concerning auditory cortex and inferior colliculus. In light of the criticism specified in the last paragraph (Statistical Methods) we would hesitate to definitely come to such a specific conclusion about discrepant trends in different structures as raised by Archer and Pappius. We believe that such conclusions are heavily dependent on the kind of statistical analysis used and therefore may not be unequivocal. In spite of the existence of different methods of statistical analysis, we believe that none of them can be used without raising some criticism when multiple data of local blood flow and metabolism are compared during different anesthetic conditions.

In conclusion, we performed a detailed statistical analysis of our data. However, we are not sure about the real impact of hundreds of comparisons and therefore followed the suggestion to omit the statistical part.

We are grateful to Drs. Archer and Pappius for giving us the opportunity to clarify several important aspects of our work.