Vagus nerve stimulation in bursts can efficiently modulate gastric contractions and contraction frequency at varying gastric pressures.

OBJECTIVE: There has been recent clinical interest in the use of vagus nerve stimulation (VNS) for treating gastrointestinal disorders as an alternative to drugs or gastric electrical stimulation. However, effectiveness of burst stimulation has not been demonstrated. We investigated the ability of bursting and continuous VNS to influence gastric and pyloric activity under a range of stimulation parameters and gastric pressures. The goals of this study were to determine which parameters could optimally excite or inhibit gastric activity. MATERIALS AND METHODS: Data were collected from 21 Sprague-Dawley rats. Under urethane anesthesia, a rubber balloon was implanted into the stomach, connected to a pressure transducer and a saline infusion pump. A pressure catheter was inserted at the pyloric sphincter and a bipolar nerve cuff was implanted onto the left cervical vagus nerve. The balloon was filled to 15 cmH2O. Stimulation trials were conducted in a consistent order; the protocol was then repeated at 25 and 35 cmH2O. The nerve was then transected and stimulation repeated to investigate directionality of effects. RESULTS: Bursting stimulation at the bradycardia threshold caused significant increases in gastric contraction amplitude with entrainment to the bursting frequency. Some continuous stimulation trials could also cause increased contractions but without frequency changes. Few significant changes were observed at the pylorus, except for frequency entrainment. These effects could not be uniquely attributed to afferent or efferent activity. SIGNIFICANCE: Our findings further elucidate the effects of different VNS parameters on the stomach and pylorus and provide a basis for future studies of bursting stimulation for gastric neuromodulation.

Feasibility of differentially measuring afferent and efferent neural activity with a single nerve cuff electrode.

OBJECTIVE: Advances in electrode technology have facilitated the development of neuroprostheses for restoring motor/sensory function in disabled individuals. Information extracted from a whole nerve, recorded using cuffs, can provide signals that control the operation of neuroprostheses. However, the amount of information that can be extracted from a tripolar cuff-which provides the highest signal-to-noise ratio (SNR)-is limited. The physical symmetry of the tripolar cuff results in neural recordings that cannot differentiate afferent versus efferent signals. In this study, we introduced a tetrapolar cuff to achieve low-noise and directionally sensitive recording. APPROACH: The tetrapolar cuff was initially designed using a computational approach. A finite element model was used to solve the electric potential generated at the electrode contacts by active electrical sources, such as the nodes of Ranvier and an artifact noise source. The resulting single fiber action potentials (SFAPs) and artifact noise signals (ANS) were used to characterize the performance of the tetrapolar configuration of the electrode length (EL) and electrode edge length (EEL) on simulated SFAP and ANS. The feasibility of using a tetrapolar cuff to differentiate afferent/efferent action potentials by applying potassium chloride in anesthetized rats was also investigated. MAIN RESULTS: Both the computational and experimental results of this study indicated that directional recording can be achieved using a tetrapolar cuff. Testing different design criteria (e.g. EL and EEL) showed that at EL values above 15 mm and EEL ⩾ 2 mm, the tetrapolar cuffs can yield larger SNRs than equally-sized tripolar cuffs. SIGNIFICANCE: This study indicated that low-noise directionally sensitive measurement of neural activity can be achieved with a tetrapolar cuff. The experimental results confirmed the feasibility of using a tetrapolar cuff to differentiate afferent/efferent signals by applying potassium chloride. Further work is needed to determine whether the tetrapolar cuff can differentiate afferent/efferent physiologically elicited neural activities.

The recording properties of a multi-contact nerve electrode as predicted by a finite element model of the canine hypoglossal nerve.

Most functional electrical stimulation (FES) systems rely only on unidirectional (i.e., efferent) activation of the target organ to yield therapeutic outcomes. For applications involving multi-fasciculated nerves, however, artificial sensors have exhibited limited results. As such, the flat-interface-nerve-electrode (FINE) is presented as a means of obtaining an effective closed-loop control system. To investigate the ability of this electrode to achieve selective recordings at physiological signal-to-noise ratio (SNR), a finite element model (JFEM) of a beagle hypoglossal nerve with an implanted FINE was constructed. Action potentials (AP) were generated at various SNR levels and the performance of the electrode was assessed with a selectivity index (0 < or = SI < or = 1; ability of the electrode to distinguish two active sources). Computer simulations yielded a selective range (0.05 < or = SI < or = 0.76) that was (1) related to the inter-fiber distance and (2) used to predict the minimum inter-fiber distance (0.23 mm < or = d < or = 1.42 mm) required for selective recording. The results of this study suggest that the FINE can record neural activity from a multi-fasciculated nerve and, more importantly, distinguish neural activity from pairs of fascicles at physiologic SNR.

Validation of fluorouracil metabolite analysis in excised tumor. Lability of anabolites.

Rapid excision and freezing of tissue commonly is assumed to preserve the molecular composition of the tissue just prior to its removal from the host. We examined the lability of radiolabeled 5-fluorouracil (FUra) and its anabolites during excision and freeze-clamping in a rat tumor model. Acid-soluble metabolites were identified by HPLC. Two rats, each bearing multiple, subcutaneously-implanted colon tumors, were treated with eniluracil (an inactivator of dihydropyrimidine dehydrogenase) to prevent catabolism of FUra and then injected intravenously with [(3)H]FUra. After 2 hr, tumors were harvested sequentially and segmented. The tumor pieces were kept at room temperature for various times up to 4 min prior to freezing. These specimens showed a decrease (P < 0.01) in labeled nucleoside triphosphate content of 13 +/- 2%/min and commensurate increases (P < 0.005) in labeled nucleoside monophosphates and nucleosides with increasing time-to-freeze. The amounts of labeled macromolecules, nucleoside diphosphates, and FUra each remained approximately constant. The study indicates that substantial errors may occur in measured tissue concentrations of pyrimidine nucleosides and nucleotides due to lability during tissue excision and freeze-clamping. Such errors can be corrected using data of the type obtained in this study.