The stomach is an electromechanical organ whose contractions are coordinated by an electrical wave called the slow wave. This activity is traditionally studied at low spatial resolution by recording from sparse electrodes either in contact with the organ or on the body surface. Recently, a few groups have mapped slow wave propagation with much higher spatial resolution by placing arrays of dozens of electrodes on the stom- ach?s surface. These studies are revealing the details of normal slow wave propagation as well as dysrhythmic patterns that occur in disease states. However, there is little information on how normal and abnormal slow waves relate to detailed spatial patterns of muscle contraction. Improved understanding is needed to improve diagnosis and treatment of debilitating gastric motility disorders that are underdiagnosed and understudied. To this end, this Bioengineering Research Grant will develop novel research instrumentation to simultane- ously record from the stomach: (1) spatiotemporal patterns of electrical activation and recovery and (2) spatio- temporal patterns of muscle contraction. The methods will be used as research tools in animal experiments.
Aim 1. Develop a system to image the membrane potential (Vm) of smooth muscle cells on the stomach?s surface. In an in vivo swine model, the stomach will be exposed and stained with a fluorescent dye whose re- sponse is modulated by Vm. Small fiducial markers will be attached to the serosal surface. Fluorescence emis- sion will be imaged with a video camera. By tracking the motion of the fiducial markers and alternating the wavelength of excitation light delivered with each camera frame, motion artifact caused by stomach contraction will be suppressed. These data will enable us to track slow waves as they propagate across the stomach.
Aim 2 : Develop an optical system to image the mechanical contraction that results from slow wave propa- gation. Additional video camera(s) mounted in a binocular fashion will be used to track the motion of the fidu- cial markers in three dimensions. From this, the deformation of the stomach?s surface will be quantified in terms of finite strain. These data will be temporally synchronized with the Vm data. These data will enable de- tailed study of the interactions between electrical and mechanical function in the stomach.
Aim 3 : Perform combined electromechanical mapping studies in normal preparations and preparations in which abnormal slow wave propagation patterns (dysrhythmias) are induced pharmacologically. Gastric empty- ing of liquid test meals will be compared with electromechanical mapping data during normal and dysrhythmic slow wave propagation. The project is a collaboration between the PI, who is an expert in developing and applying novel optical mapping methods for the heart, and Auckland-based investigators, who are experts in gastrointestinal physiol- ogy and mapping. We expect that success of this project will lead to future collaborations applying the new technology to problems in physiology and medicine.
A large healthcare burden is associated with stomach motility disorders such as gastroparesis and func- tional dyspepsia. The proposed project will develop new research tools for studying the electrical and mechani- cal function of the stomach with a view toward improved understanding, diagnosis, and treatment of motility disorders.
