Background/Objectives: To better understand the mechanism of action of deep brain stimulation (DBS) for epilepsy and to investigate implantable device features, it is desirable to have a large animal model to evaluate clinical-grade systems. This study assessed the suitability of an ovine model of epilepsy for this purpose. Methods: Animals were anesthetized for surgery and 1.5 T MRIs collected. Unilateral anterior thalamic DBS leads, hippocampal depth electrodes and catheters were implanted using a frameless stereotactic system. Evoked responses and local field potentials were collected and stored for off-line analysis. Results: Despite limited neuroanatomic information for this species, it was possible to reliably implant leads into the target structures using MR-guided techniques. Stimulation of these regions produced robust evoked potentials within this circuit that were dependent on stimulus location and parameters. High-frequency thalamic DBS produced a clear inhibition of both spontaneous and penicillin-induced ictal activity in the hippocampus which far outlasted the duration of the stimulation. Conclusions: These preliminary results suggest that the sheep model may be useful for further investigation of DBS for epilepsy. The demonstration of marked suppression of network excitability with high-frequency stimulation supports a potential therapeutic mechanism for this DBS therapy.

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Background and Objective: Intrathecal drug delivery catheter malfunctions are a principal cause of therapy interruption. We determined that normal baseline intrathecal cerebrospinal fluid (CSF) pressure recordings could be obtained in an ovine model and in a catheter dislodgement scenario. Methods: Two sheep were implanted with spinal catheters: 2 in the T₆ epidural space in sheep No. 1; 1 T₆ intrathecal catheter plus 1 L₂ epidural catheter with a deliberate CSF leak to simulate dislodgement in sheep No. 2. Pressure waves were recorded intraoperatively and at multiple times after the implantation in the awake condition. On day 21, the animals were anesthetized for pressure recordings while on and temporarily off mechanical ventilation. They were then necropsied. Results: CSF pressure waves were obtained in this animal model under anesthesia with or without mechanical ventilation and in the awake state. Fluid accumulation at the tip of a dislodged (epidural) catheter temporarily caused apparent coupling of fluid pressures across the dura. An unintentional extraspinal fluid collection in sheep No. 2 was associated with a raised baseline epidural pressure. Conclusions: These findings support the notion that pressure sensors can play a role in determining the status of intraspinal drug delivery catheters.

Background We determined whether intrathecally delivering the same daily dose of morphine (MS) at a fixed concentration of 25 mg/mL by periodic boluses versus continuous infusion would reduce intrathecal mass (IMs) formation in dogs. Methods Adult dogs (hound cross, n = 32) were implanted with intrathecal catheters connected to SynchroMed II infusion pumps. Animals were randomly assigned to receive infusion of 0.48 mL/day of saline or MS dosing (12 mg/day at 25 mg/mL) as boluses: x1 (q24hour), x2 (q12hour), x4 (q6hour), or x8 (q3hour) given at the rate of 1000 μL/hour, or as a continuous infusion (25 mg/mL/20 μL/hour). Results With IT saline, minimal pathology was noted. In contrast, animals receiving morphine displayed spinally compressing durally derived masses with the maximal cross‐sectional area being greatest near the catheter tip. Histopathology showed that IMs consisted of fibroblasts in a collagen (type 1) matrix comprised of newly formed collagen near the catheter and mature collagen on the periphery of the mass. The rank order of median cross‐sectional mass area (mm2) was: Saline: 0.7 mm2; x2: 1.8 mm2; x4: 2.7 mm2; x1: 2.7 mm2; x8: 4.2 mm2; Continuous: 8.1 mm2, with statistical difference from saline being seen with continuous (p < 0.0001) and x8 (p < 0.05). Bench studies with a 2D diffusion chamber confirmed an increase in dye distribution and lower peak concentrations after bolus delivery versus continuous infusion of dye. Conclusions Using multiple bolus dosing, IMs were reduced as compared to continuous infusion, suggesting relevance of bolus delivery in yielding reduced intrathecal masses.

Prosthetic heart valves undergo mandatory preclinical animal testing prior to human clinical trials. Historically, a non-site-specific placement of a valve prosthesis has been commonly performed; however, recently site-specific placement continues to attract interest. Various animal models have been used for preclinical evaluation of both aortic and mitral valve prostheses; however, a universally accepted animal model for orthotopic total aortic root replacement with acceptable early and late mortality for long-term evaluation has been lacking. This article reports a successful orthotopic model for placement of tissue valve conduit prosthesis for total aortic root replacement in adult sheep. This model utilized preoperative echocardiographic assessment, specific intraoperative surgical techniques, and both early and late postoperative management therapies. The combination of all of these components resulted in a successful model for orthotopic placement of a tissue valve prosthesis for total aortic root replacement in adult sheep for potential long-term assessment.