Development of Multiple Probe Microdialysis Sampling Techniques for Site-Specific Monitoring in the Stomach

Abstract

Microdialysis sampling is a technique used extensively to monitor analytes within numerous tissues. Although the capability of implanting multiple probes into a single animal exists, typical experiments are performed using a single probe. When sampling from heterogeneous tissues (e.g. the stomach), differences between each tissue layer cannot be determined by sampling from one probe. Microdialysis probes implanted into each layer would better represent sampling in the stomach. The focus of this research was to develop multiple probe microdialysis sampling techniques to simultaneously sample different tissue layers of the stomach. Furthermore, to augment the application of this approach, multiple probe microdialysis sampling was developed to compare different tissue types (i.e. diseased and healthy tissue in the same stomach). Initially, methods of probe implantation simultaneously in the lumen, mucosa, submucosa and the blood of a rat were developed. Histology confirmed that microdialysis probes were successfully implanted in both the mucosa and submucosa. Alternatively, to compare normal and ulcerated tissue, methods of multiple probe microdialysis sampling in the lumen, submucosa of ulcerated and normal tissue and in blood were developed. Methods of gastric ulcer induction were optimized and probes were successfully implanted into the ulcerated and normal tissue, with probe location confirmed through histology. To determine the significance of a multiple probe approach, this method was used to monitor drug absorption in both normal and ulcerated stomachs. Concentration-time curves and pharmacokinetics analyses were performed to determine differences in drug concentrations from each probe location. Results from dosed test compounds were determined to be comparable with predicted absorption rates. Differences in drug concentration were observed between the mucosa and submucosa and increased concentrations were determined in ulcerated relative to normal tissue. Overall, the research presented illustrates that microdialysis probes can be successfully implanted in different stomach tissue layers simultaneously and that this approach can be used to monitor different tissue layers in the stomach as well as directly compare ulcerated and normal tissue. A multiple probe approach serves as improvements to current uses of microdialysis sampling in the stomach as well as traditional sampling methods to measure drug absorption in the GI tract.