Eaker, Diane R.

Occlusion of coronary vasa vasorum (VV) leads to hypoperfusion of the arterial vessel wall (AVW) possibly resulting in impaired solute transport. We hypothesize that high cholesterol (HC) facilitates development of atherogenesis in hypoperfused areas. Swine (40) underwent injection of gold‐coated μspheres (100μm) in left coronary artery. After the procedure 13 swine were studied immediately, 13 were fed a standard (C) and 14 a HC diet for 3 months prior to study. The LADs were harvested and snap‐frozen (cryo micro‐CT scanning). Hypoperfused areas in the AVW were defined by local reduction of CT‐values. The distance of μsphere to lumen (x) was measured, and foam/fat cells/mm 2 (f/fc) in hypoperfused and perfused areas were counted using histology. Linear relationship between x and hypoperfused AVW. In HC the f/fc # in media of hypoperfused areas is higher than in C (p=0.001). In HC f/fc # is higher in hypoperfused AVW areas compared to adjacent perfused areas (p<0.05). In C there is no difference in f/fc # between hypoperfused and perfused areas (p=0.92). In C and HC the f/fc # in intima of perfused, as well as in hypoperfused, areas is not different (p=0.9/0.5). Occlusion of VV leads to increased susceptibility of hypoperfused AVW areas for precursors of atherosclerosis with HC diet. The linear relationship of hypoperfused area to μsphere distance suggests that VV function as a plexus rather than a vascular tree. This study was supported by NIH grant HL065342.

Object Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS “smart” device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Methods To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between −0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of −0.4 V between scans. Results By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency. Conclusions Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application.