Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity.

OBJECTIVES: Cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin. METHODS: DSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity. RESULTS: DSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01). CONCLUSION: It is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH.

Effects of buprenorphine, butorphanol or tramadol premedication on anaesthetic induction with alfaxalone in common marmosets (Callithrix jacchus).

OBJECTIVE: To investigate the clinical and physiological effects of intravenous (IV) alfaxalone alone or in combination with buprenorphine, butorphanol or tramadol premedication in marmosets. STUDY DESIGN: Prospective, randomized, blinded, crossover design. ANIMALS: Nine healthy marmosets (391 ± 48 g, 3.7 ± 2.2 years old). METHODS: Meloxicam 0.20 mg kg-1 subcutaneously, atropine 0.05 mg kg-1 intramuscularly (IM) and either buprenorphine 20 µg kg-1 IM (BUP-A), butorphanol 0.2 mg kg-1 IM (BUT-A), tramadol 1.5 mg kg-1 IM (TRA-A) or no additional drug (control) were administered to all marmosets as premedication. After 1 hour, anaesthesia was induced with 16 mg kg-1 alfaxalone IV. All animals received all protocols. The order of protocol allocation was randomized with a minimum 28 day wash-out period. During anaesthesia, respiratory and pulse rates, rectal temperature, haemoglobin oxygen saturation, arterial blood pressure, palpebral and pedal withdrawal reflexes and degree of muscle relaxation were assessed and recorded every 5 minutes. Quality of induction and recovery were assessed. Duration of induction, immobilization and recovery were recorded. Blood samples were analysed for aspartate aminotransferase, creatine kinase and lactate dehydrogenase concentrations. The protocols were compared using paired t tests, Wilcoxon's signed-rank test with Bonferroni's corrections and linear mixed effect models where appropriate. RESULTS: Out of nine animals, apnoea was noted in eight animals administered protocol BUP-A and two animals administered protocol BUT-A. With TRA-A and control protocols, apnoea was not observed. No other significant differences in any of the parameters were found; however, low arterial blood pressures and hypoxia occurred in TRA-A. CONCLUSIONS AND CLINICAL RELEVANCE: Our study employing different premedications suggests that the previously published dose of 16 mg kg-1 alfaxalone is too high when used with premedication because we found a high incidence of complications including apnoea (BUP-A), hypotension and hypoxaemia (TRA-A). Appropriate monitoring and countermeasures are recommended.

A novel, non-adhesive, precipitating liquid embolic implant with intrinsic radiopacity: feasibility and safety animal study.

OBJECTIVES: To evaluate a novel, ready-to-use, iodinated polyvinyl alcohol polymer embolic implant. METHODS: Under good laboratory practice conditions, 26 pigs were investigated. A complex arteriovenous malformation (AVM) model was created in 16 animals, and a simple rete model was used in the remaining 10 animals. The novel material was used for embolization in 22 animals, and a commercially available liquid embolic material in 4 animals as a control group. Animals were killed at 2 days, 3 months and 6 months. Feasibility, efficacy and safety were evaluated radiologically, clinically and histologically. RESULTS: Preparation was easy, without risk of catheter clogging or adhesiveness. Embolic delivery was well controlled under subtracted fluoroscopy. Visibility was homogeneous throughout the injection and the material behaved cohesively upon delivery. Best lesion penetration was obtained with the use of proximal microballoon occlusion. Unforeseen over-dilution of the test material by DMSO prefilled in the microballoon hub changed the material properties and caused inadvertent cerebral embolization leading to death in five animals. This phenomenon was avoided by practical measures. The casts produced no beam-hardening artefacts on CT scans. Histology showed excellent biocompatibility. CONCLUSIONS: Embolization with this novel, iodinated, precipitating polymer was feasible and effective. Care should be taken during delivery to avoid over-dilution of the material by prefilled DMSO. The material is promising for embolization of AVMs and hypervascular lesions. KEY POINTS: • The intrinsically opaque precipitating polymer has adequate fluoroscopic visibility • The polymer does not induce shading or beam-hardening artefacts on CT • The novel liquid embolic material does not require lengthy preparation • Lack of implant adherence reduces the risk of entrapment of the delivery catheter.

Plasma concentrations of transdermal fentanyl and buprenorphine in pigs (Sus scrofa domesticus).

OBJECTIVE: To determine the absorption characteristics of fentanyl and buprenorphine administered transdermally in swine. STUDY DESIGN: A randomized comparative experimental trial. ANIMALS: Twenty-four Yorkshire gilts weighing 27.8±2.2 kg (mean±standard deviation). METHODS: Animals were randomly assigned to different doses of transdermal patches (TPs) of fentanyl (50 µg hour-1, 75 µg hour-1 and 100 µg hour-1) or buprenorphine (35 µg hour-1 and 70 µg hour-1), once or twice. Thirteen blood samples were obtained for each TP applied. Plasma concentrations were determined, and the area under the curve, peak serum concentration (Cmax) and time to Cmax were calculated. RESULTS: Fentanyl: Cmax was observed at different time points: for the first TP application: 30 hours for 50 µg hour-1, 6 hours for 75 µg hour-1 and 100 µg hour-1 patches; and for the second TP application: 30 hours for 50 µg hour-1 and 36 hours for 75 µg hour-1 patches. Buprenorphine: serum concentrations were not detected for the 35 µg hour-1 patch; Cmax was observed at different times for the 70 µg hour-1 patch: 18 hours (n = 1), 24 hours (n = 3), 30 hours (n = 1) and 42 hours (n = 1) after application of the first patch and 12 hours after the second patch. CONCLUSIONS AND CLINICAL RELEVANCE: A relevant serum concentration obtained with fentanyl TP dosed at 75 µg hour-1 or 100 µg hour-1suggests that TPs could represent an analgesia option for laboratory pigs weighing 25-30 kg. As concentrations of buprenorphine were variable, this study does not support the use of buprenorphine TPs in pigs. Consecutive fentanyl or buprenorphine TPs did not provide reliable serum concentrations. Further pharmacokinetic studies and analgesiometric tests in swine are needed to confirm the clinical adequacy of TPs.

Clinical evaluation of intranasal medetomidine-ketamine and medetomidine-S(+)-ketamine for induction of anaesthesia in rabbits in two centres with two different administration techniques.

OBJECTIVE: The aim was to compare efficacy and side effects of induction with medetomidine-ketamine or medetomidine-S(+)-ketamine by intranasal (IN) instillation in rabbits and to evaluate both protocols during subsequent isoflurane anaesthesia. STUDY DESIGN: Prospective, blinded, randomized experimental study in two centres. ANIMALS: Eighty-three healthy New Zealand White rabbits undergoing tibial or ulnar osteotomy. METHODS: Medetomidine (0.2 mg kg-1) with 10 mg kg-1 ketamine (MK) or 5 mg kg-1 S(+)-ketamine (MS) was administered IN to each rabbit in a randomized fashion. In Centre 1 (n = 42) rabbits were held in sternal recumbency, and in Centre 2 (n = 41) in dorsal recumbency, during drug instillation. Adverse reactions were recorded. If a rabbit swallowed during endotracheal intubation, half of the initial IN dose was repeated and intubation was re-attempted after 5 minutes. Anaesthesia was maintained with isoflurane. Heart rate, blood pressure, endtidal carbon dioxide concentration and blood gases were recorded. Data were analysed using Student's t-test, Mann-Whitney test and Fisher's exact test. RESULTS: In all, 39 animals were assigned to the MK group and 44 to the MS group. Two rabbits in the MS group held in dorsal recumbency died after instillation of the drug. Eight (MK) and 11 rabbits (MS) were insufficiently anaesthetized and received a second IN dose. One rabbit in MK and three in MS required an isoflurane mask induction after the second IN dose. There were no significant differences between treatments for induction, intraoperative data, blood gas values and recovery data. CONCLUSION AND CLINICAL RELEVANCE: This study indicated that medetomidine-ketamine and medetomidine-S(+)-ketamine were effective shortly after IN delivery, but in dorsal recumbency IN administration of S(+)-ketamine led to two fatalities. Nasal haemorrhage was noted in both cases; however, the factors leading to death have not been fully elucidated.

A new-generation, low-permeability flow diverting device for treatment of saccular aneurysms.

OBJECTIVES: We report a preclinical comparative study of a 96-strand braided flow diverter. METHODS: The 96-strand braided device was compared with the currently commercially available flow diverter with 48 strands. The devices were implanted across the neck of 12 elastase-induced aneurysms in New Zealand White rabbits and followed for 1 and 3 months (n = 6 respectively). Aneurysm occlusion rates, parent artery stenosis and patency of jailed branch occlusions were assessed by angiography, histology and scanning electron microscopy studies. RESULTS: It was feasible to navigate and implant the 96-strand device over the aneurysm orifice in all cases. At follow-up two aneurysms in the 48-strand vs. one in the 96-strand group were not occluded. This aneurysm from the 96-strand group however had a tracheal branch arising from the sac and showed a reverse remodelling of the vascular pouch at 3 months. In the occluded aneurysms, the parent artery was always completely reconstructed and the aneurysm orifice was sealed with neointimal tissue. No in-stent stenosis or jailed branch artery occlusion was observed. CONCLUSIONS: The 96-strand flow diverter proved to be safe, biocompatible and haemodynamically effective, induced stable occlusion of aneurysms and led to reverse remodelling of the parent artery. KEY POINTS: • Flow diversion has been introduced to improve endovascular treatment of cerebral aneurysms • A new low-permeability flow diverter is feasible for parent artery reconstruction. • The Silk 96 flow diverter appears effective at inducing aneurysm healing. • The covered branches remained patent at follow-up.

Preliminary study on carprofen concentration measurements after transcutaneous treatment with Vetdrop® in a microfracture joint defect model in sheep.

BACKGROUND: The present preliminary study describes concentration time courses of the NSAID carprofen in the plasma and synovial fluid in a microfrature sheep model after transcutaneous treatments with a novel application device (Vetdrop®). To treat circumscribed inflammatory processes a transcutaneous application device could potentially be beneficial. After transcutaneous application normally lower systemic concentrations are measured which may reduce the incidence of side effects, whereas efficacy is still maintained. In this study carprofen was used based on its capacity to provide analgesia after orthopaedic procedures in sheep and it is considered that it may have a positive influence on the healing of cartilage in low concentrations. RESULTS: In all transcutaneously treated animals, carprofen plasma concentrations exceeded those of synovial fluid, although plasma levels remained significantly reduced (300-fold) as compared to carprofen administered intravenously. Furthermore, in contrast to the intravenously treated animals, a modest accumulation of carprofen in plasma and synovial fluid was observed in the transcutaneously treated animals over the 6-week treatment period. CONCLUSIONS: The transcutaneously administered carprofen using the Vetdrop® device penetrated the skin and both, plasma- and synovial concentrations could be measured repeatedly over time. This novel device may be considered a valuable transcutaneous drug delivery system.

Haptoglobin Attenuates Cerebrospinal Fluid Hemoglobin-Induced Neurological Deterioration in Sheep.

Secondary brain injury (SBI) occurs with a lag of several days post-bleeding in patients with aneurysmal subarachnoid hemorrhage (aSAH) and is a strong contributor to mortality and long-term morbidity. aSAH-SBI coincides with cell-free hemoglobin (Hb) release into the cerebrospinal fluid. This temporal association and convincing pathophysiological concepts suggest that CSF-Hb could be a targetable trigger of SBI. However, sparse experimental evidence for Hb's neurotoxicity in vivo defines a significant research gap for clinical translation. We modeled the CSF-Hb exposure observed in aSAH patients in conscious sheep, which allowed us to assess neurological functions in a gyrencephalic species. Twelve animals were randomly assigned for 3-day bi-daily intracerebroventricular (ICV) injections of either Hb or Hb combined with the high-affinity Hb scavenger protein haptoglobin (Hb-Hp, CSL888). Repeated CSF sampling confirmed clinically relevant CSF-Hb concentrations. This prolonged CSF-Hb exposure over 3 days resulted in disturbed movement activity, reduced food intake, and impaired observational neuroscores. The Hb-induced neurotoxic effects were significantly attenuated when Hb was administered with equimolar haptoglobin. Preterminal magnetic resonance imaging (MRI) showed no CSF-Hb-specific structural brain alterations. In both groups, histology demonstrated an inflammatory response and revealed enhanced perivascular histiocytic infiltrates in the Hb-Hp group, indicative of adaptive mechanisms. Heme exposure in CSF and iron deposition in the brain were comparable, suggesting comparable clearance efficiency of Hb and Hb-haptoglobin complexes from the intracranial compartment. We identified a neurological phenotype of CSF-Hb toxicity in conscious sheep, which is rather due to neurovascular dysfunction than structural brain injury. Haptoglobin was effective at attenuating CSF-Hb-induced neurological deterioration, supporting its therapeutic potential.

Bone augmentation for cancellous bone- development of a new animal model.

BACKGROUND: Reproducible and suitable animal models are required for in vivo experiments to investigate new biodegradable and osteoinductive biomaterials for augmentation of bones at risk for osteoporotic fractures. Sheep have especially been used as a model for the human spine due to their size and similar bone metabolism. However, although sheep and human vertebral bodies have similar biomechanical characteristics, the shape of the vertebral bodies, the size of the transverse processes, and the different orientation of the facet joints of sheep are quite different from those of humans making the surgical approach complicated and unpredictable. Therefore, an adequate and safe animal model for bone augmentation was developed using a standardized femoral and tibia augmentation site in sheep. METHODS: The cancellous bone of the distal femur and proximal tibia were chosen as injection sites with the surgical approach via the medial aspects of the femoral condyle and proximal tibia metaphysis (n = 4 injection sites). For reproducible drilling and injection in a given direction and length, a custom-made c-shaped aiming device was designed. Exact positioning of the aiming device and needle positioning within the intertrabecular space of the intact bone could be validated in a predictable and standardized fashion using fluoroscopy. After sacrifice, bone cylinders (Ø 32 mm) were harvested throughout the tibia and femur by means of a diamond-coated core drill, which was especially developed to harvest the injected bone area exactly. Thereafter, the extracted bone cylinders were processed as non-decalcified specimens for µCT analysis, histomorphometry, histology, and fluorescence evaluation. RESULTS: The aiming device could be easily placed in 63 sheep and assured a reproducible, standardized injection area. In four sheep, cardiovascular complications occurred during surgery and pulmonary embolism was detected by computed tomography post surgery in all of these animals. The harvesting and evaluative methods assured a standardized analysis of all samples. CONCLUSIONS: This experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty.

Digital light 3D printing of customized bioresorbable airway stents with elastomeric properties.

Central airway obstruction is a life-threatening disorder causing a high physical and psychological burden to patients. Standard-of-care airway stents are silicone tubes, which provide immediate relief but are prone to migration. Thus, they require additional surgeries to be removed, which may cause tissue damage. Customized bioresorbable airway stents produced by 3D printing would be highly needed in the management of this disorder. However, biocompatible and biodegradable materials for 3D printing of elastic medical implants are still lacking. Here, we report dual-polymer photoinks for digital light 3D printing of customized and bioresorbable airway stents. These stents exhibit tunable elastomeric properties with suitable biodegradability. In vivo study in healthy rabbits confirmed biocompatibility and showed that the stents stayed in place for 7 weeks after which they became radiographically invisible. This work opens promising perspectives for the rapid manufacturing of the customized medical devices for which high precision, elasticity, and degradability are sought.

Determination of the minimum alveolar concentration of isoflurane in Shetland ponies using constant current or constant voltage electrical stimulation.

OBJECTIVE: To determine the minimum alveolar concentration (MAC) of isoflurane in Shetland ponies using a sequence of three different supramaximal noxious stimulations at each tested concentration of isoflurane rather than a single stimulation. STUDY DESIGN: Prospective, experimental trial. ANIMALS: Seven 4-year-old, gelding Shetland ponies. METHODS: The MAC of isoflurane was determined for each pony. Three different modes of electrical stimulation were applied consecutively (2 minute intervals): two using constant voltage (90 V) on the gingiva via needle- (CVneedle) or surface-electrodes (CVsurface) and one using constant current (CC; 40 mA) via surface electrodes applied to the skin over the digital nerve. The ability to clearly interpret the responses as positive, the latency of the evoked responses and the inter-electrode resistance were recorded for each stimulus. RESULTS: Individual isoflurane MAC (%) values ranged from 0.60 to 1.17 with a mean (+/-SD) of 0.97 (+/-0.17). The responses were more clearly interpreted with CC, but did not reach statistical significance. The CVsurface mode produced responses with a longer delay. The CVneedle mode was accompanied by variable inter-electrode resistances resulting in uncontrolled stimulus intensity. At 0.9 MAC, the third stimulation induced more positive responses than the first stimulation, independent of the mode of stimulation used. CONCLUSIONS: The MAC of isoflurane in the Shetland ponies was lower than expected with considerable variability among individuals. Constant current surface electrode stimulations were the most repeatable. A summation over the sequence of three supramaximal stimulations was observed around 0.9 MAC. CLINICAL RELEVANCE: The possibility that Shetland ponies require less isoflurane than horses needs further investigation. Constant current surface-electrode stimulations were the most repeatable. Repetitive supramaximal stimuli may have evoked movements at isoflurane concentrations that provide immobility when single supramaximal stimulation was applied.

Diffusion-weighted and perfusion-weighted magnetic resonance imaging of the prostate gland of healthy adult dogs.

OBJECTIVE: To describe diffusion and perfusion characteristics of the prostate gland of healthy sexually intact adult dogs as determined by use of diffusion-weighted and perfusion-weighted MRI. ANIMALS: 12 healthy sexually intact adult Beagles. PROCEDURES: Ultrasonography of the prostate gland was performed. Subsequently, each dog was anesthetized, and morphological, diffusion-weighted, and perfusion-weighted MRI of the caudal aspect of the abdomen was performed. The apparent diffusion coefficient was calculated for the prostate gland parenchyma in diffusion-weighted MRI images in the central ventral and peripheral dorsal areas. Perfusion variables were examined in multiple regions of interest (ROIs) in the ventral and dorsal areas of the prostate gland and in the gluteal musculature. Signal intensity was determined, and a time-intensity curve was generated for each ROI. RESULTS: Results of ultrasonographic examination of the prostate gland revealed no abnormalities for any dog. Median apparent diffusion coefficient of the prostate gland was 1.51 × 10-3 mm2/s (range, 1.04 × 10-3 mm2/s to 1.86 × 10-3 mm2/s). Perfusion-weighted MRI variables for the ROIs differed between the prostate gland parenchyma and gluteal musculature. CONCLUSIONS AND CLINICAL RELEVANCE: Results provided baseline information about diffusion and perfusion characteristics of the prostate gland in healthy sexually intact adult dogs. Additional studies with dogs of various ages and breeds, with and without abnormalities of the prostate gland, will be necessary to validate these findings and investigate clinical applications.

Haptoglobin administration into the subarachnoid space prevents hemoglobin-induced cerebral vasospasm.

Delayed ischemic neurological deficit (DIND) is a major driver of adverse outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH), defining an unmet need for therapeutic development. Cell-free hemoglobin that is released from erythrocytes into the cerebrospinal fluid (CSF) is suggested to cause vasoconstriction and neuronal toxicity, and correlates with the occurrence of DIND. Cell-free hemoglobin in the CSF of patients with aSAH disrupted dilatory NO signaling ex vivo in cerebral arteries, which shifted vascular tone balance from dilation to constriction. We found that selective removal of hemoglobin from patient CSF with a haptoglobin-affinity column or its sequestration in a soluble hemoglobin-haptoglobin complex was sufficient to restore physiological vascular responses. In a sheep model, administration of haptoglobin into the CSF inhibited hemoglobin-induced cerebral vasospasm and preserved vascular NO signaling. We identified 2 pathways of hemoglobin delocalization from CSF into the brain parenchyma and into the NO-sensitive compartment of small cerebral arteries. Both pathways were critical for hemoglobin toxicity and were interrupted by the large hemoglobin-haptoglobin complex that inhibited spatial requirements for hemoglobin reactions with NO in tissues. Collectively, our data show that compartmentalization of hemoglobin by haptoglobin provides a novel framework for innovation aimed at reducing hemoglobin-driven neurological damage after subarachnoid bleeding.

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration in Shetland ponies sedated with xylazine.

The pharmacokinetics of ketamine and norketamine enantiomers after administration of intravenous (IV) racemic ketamine (R-/S-ketamine; 2.2 mg/kg) or S-ketamine (1.1 mg/kg) to five ponies sedated with IV xylazine (1.1mg/kg) were compared. The time intervals to assume sternal and standing positions were recorded. Arterial blood samples were collected before and 1, 2, 4, 6, 8 and 13 min after ketamine administration. Arterial blood gases were evaluated 5 min after ketamine injection. Plasma concentrations of ketamine and norketamine enantiomers were determined by capillary electrophoresis and were evaluated by non-linear least square regression analysis applying a monocompartmental model. The first-order elimination rate constant was significantly higher and elimination half-life and mean residence time were lower for S-ketamine after S-ketamine compared to R-/S-ketamine administration. The maximum concentration of S-norketamine was higher after S-ketamine administration. Time to standing position was significantly diminished after S-ketamine compared to R-/S-ketamine. Blood gases showed low-degree hypoxaemia and hypercarbia.

Evaluation of administration of isoflurane at approximately the minimum alveolar concentration on depression of a nociceptive withdrawal reflex evoked by transcutaneous electrical stimulation in ponies.

OBJECTIVE: To investigate effects of isoflurane at approximately the minimum alveolar concentration (MAC) on the nociceptive withdrawal reflex (NWR) of the forelimb of ponies as a method for quantifying anesthetic potency. ANIMALS: 7 healthy adult Shetland ponies. PROCEDURE: Individual MAC (iMAC) for isoflurane was determined for each pony. Then, effects of isoflurane administered at 0.85, 0.95, and 1.05 iMAC on the NWR were assessed. At each concentration, the NWR threshold was defined electromyographically for the common digital extensor and deltoid muscles by stimulating the digital nerve; additional electrical stimulations (3, 5, 10, 20, 30, and 40 mA) were delivered, and the evoked activity was recorded and analyzed. After the end of anesthesia, the NWR threshold was assessed in standing ponies. RESULTS: Mean +/- SD MAC of isoflurane was 1.0 +/- 0.2%. The NWR thresholds for both muscles increased significantly in a concentration-dependent manner during anesthesia, whereas they decreased in awake ponies. Significantly higher thresholds were found for the deltoid muscle, compared with thresholds for the common digital extensor muscle, in anesthetized ponies. At each iMAC tested, amplitudes of the reflex responses from both muscles increased as stimulus intensities increased from 3 to 40 mA. A concentration-dependent depression of evoked reflexes with reduction in slopes of the stimulus-response functions was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthetic-induced changes in sensory-motor processing in ponies anesthetized with isoflurane at concentrations of approximately 1.0 MAC can be detected by assessment of NWR. This method will permit comparison of effects of inhaled anesthetics or anesthetic combinations on spinal processing in equids.

Experimental stenting of the posterior mitral leaflet to correct prolapse in mitral valve insufficiency.

OBJECTIVE: This study investigated the use of a new concept of mitral valve reconstruction using a novel device to stent the posterior mitral leaflet in combination with semicircular annuloplasty. Modern mitral valve repair is an accepted modality and a routine procedure for treatment of degenerative mitral valve insufficiency. One of the most common mechanisms of mitral valve insufficiency is leaflet prolapse. In the majority of cases the posterior leaflet is dysfunctional and therapeutic reconstruction of the PII flail leaflet segment involves quadrangular resection which is usually combined to mitral annulo-plasty with a ring. A new time-saving concept of mitral valve reconstruction by stenting the posterior mitral leaflet in combination with semicircular annuloplasty is presented. METHODS: The new mitral valve reconstruction device (Shelhigh MitroFast, Shelhigh, Inc., Union, NJ, USA) was implanted in four adult sheep. It is constructed as an annuloplasty ring in combination with a posterior leaflet stent. The device has the shape of a closed posterior leaflet and forms a "buttress" against which the anterior leaflet can coapt. RESULTS: Every implantation of a MitroFast device could be performed in less than 30 minutes. After implantation of the device, all animals could be successfully weaned from CPB. Invasively measured left atrial pressure was below 12 mm Hg in all animals. After chest closure, transoesophageal echocardiography revealed a competent mitral valve in all animals, without any inflow restriction in three animals, and suspected mild stenosis in one animal. CONCLUSIONS: In this experimental model, implantation of the newly designed annuloplasty ring with stenting the posterior mitral leaflet avoids extensive and time-consuming reconstructive surgery on a flail posterior leaflet. Implantation of the device resulted in favorable short-term hemodynamic effects. Implantation technique of the device is simple, the potential for minimal invasive implantation of a conceptual similar device will be further investigated.

Dynamization at the near cortex in locking plate osteosynthesis by means of dynamic locking screws: an experimental study of transverse tibial osteotomies in sheep.

BACKGROUND: Locking plates are widely used in fracture fixation, mainly for meta-diaphyseal fractures, comminuted fractures, fractures with a critical-size bone defect, periprosthetic fractures, osteotomies, and fractures in osteoporotic bone. The aim of this animal study was to evaluate the effect on bone-healing of dynamization of locking plate constructs by means of new 5.0-mm dynamic locking screws (in the DLS group), which allow near-cortex micromotion, compared with a more rigid construct utilizing standard bicortical locking-head screws (in the LS group). Use of dynamic locking screws allows modulation of the stiffness of existing locking compression plate systems via parallel interfragmentary micromotion. METHODS: A standardized diaphyseal tibial osteotomy (90°, 3-mm fracture gap) was performed and stabilized with a six-hole large-fragment locking compression plate in twelve female sheep (six in each group). Radiographs were made postoperatively and then weekly from week three until sacrifice at nine weeks. Macroscopic, biomechanical, histologic, and radiographic assessments and microcomputed tomography were performed. RESULTS: The callus in the tested specimens in the DLS group had better biomechanical stability, with a significantly greater maximum failure moment (mean and standard deviation [SD] as a percentage of intact, 55.15 ± 20.65 compared with 26.80 ± 14.96 in the LS group; p = 0.021). The DLS group also had greater periosteal callus volume at the near cortex (mean volume and SD as a percentage of the tibial shaft volume, 36.21% ± 10.08% compared with 18.98% ± 8.61% in the LS group; p = 0.026) and in the intercortical region (mean volume and SD as a percentage of the bone volume of the tibial shaft, 3.56% ± 0.52% compared with 2.64% ± 0.98% in the LS group; p = 0.045), as shown by microcomputed tomography. The DLS group also had significantly greater torsional stiffness (mean and SD as a percentage of intact, 84.88 ± 13.51 compared with 58.89 ± 20.61 in the LS group; p = 0.027). CONCLUSIONS: Controlled micromotion and nearly homogeneous interfragmentary strain at the fracture site, together with the stable bicortical fixation achieved by the new dynamic locking screw, led to more uniform callus formation, significantly more callus formation at the near cortex, and biomechanically more competent bone-healing compared with use of rigid locking plate constructs with locking-head screws.

A synthetic fraction of feline facial pheromones calms but does not reduce struggling in cats before venous catheterization.

OBJECTIVE: To evaluate whether a synthetic analogue of feline facial pheromone (FFP) calms cats before, and reduces struggling during intravenous catheterization. DESIGN: Block-randomized, 'blinded' clinical trial. ANIMALS: Seventy-seven healthy cats presented for elective surgery. PROCEDURE: Cats given glycopyrrolate and oxymorphone were assigned to one of four treatments: acepromazine and exposure to FFP (aceFFP); acepromazine and exposure to a placebo (acePlac); exposure to FFP only (FFP) and exposure to placebo only (Plac). The behaviour of cats was recorded on videotape for evaluation by assessors unaware of treatment group. Cats' veins were then catheterized by veterinary students unaware of the study protocol. Based on each cat's response to catheterization, the student independently decided whether intramuscular ketamine was required. RESULTS: Cats in the aceFFP group appeared to be calmer than acePlac cats on the basis of head position and their location in the cage (suggesting benefit from FFP among cats receiving acepromazine) but appeared to be less sedated. Cats in the aceFFP group also appeared to be calmer than FFP cats on the basis of head position and location in the cage. Feline facial pheromone cats were also calmer than Plac cats when compared using body and leg position. Exposure to FFP did not significantly reduce struggling at catheterization, nevertheless, the students were able to catheterize the veins in all cats. CONCLUSION AND CLINICAL RELEVANCE: There were no detrimental behavioural effects associated with either FFP or acepromazine. The FFP had additional calming effects in cats given acepromazine and, to a lesser degree, helped to calm cats that were not given acepromazine. Feline facial pheromone helps to calm cats in unfamiliar surroundings.