Inhibition and facilitation of nociceptively evoked muscular activity by fentanyl or dexmedetomidine in isoflurane-anaesthetized pigs.

OBJECTIVE: To investigate motor and cardiovascular responses to dexmedetomidine or fentanyl in isoflurane-anaesthetized pigs. STUDY DESIGN: Experimental, balanced, block randomized, two-group design. ANIMALS: A group of 16 crossbred pigs, 55 ± 8 days (mean ± standard deviation) old. METHODS: Deltoid electromyography (EMG) was recorded during isoflurane anaesthesia. Electrical stimulation using 5, 10, 20 and 40 mA of the distal right thoracic limb elicited a nociceptive withdrawal reflex (NWR), quantified by the area under the curve (AUC) for the simulation intensity versus EMG amplitude response curve. Latency to movement evoked by clamping a claw for maximum 60 seconds was noted. Arterial blood pressure and pulse rate were recorded. Data were sampled at baseline and during dexmedetomidine 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 µg kg-1 hour-1 or fentanyl 5, 10, 20, 40, 80 and 160 µg kg-1 hour-1 infusions. The influence of infusion rate on NWR AUC and spontaneous EMG was analysed using a mixed model, with p < 5%. RESULTS: NWR AUC increased at fentanyl 5 µg kg-1 hour-1 but decreased at fentanyl 40, 80 and 160 µg kg-1 hour-1 and dexmedetomidine 4.0 and 8.0 µg kg-1 hour-1. All pigs at fentanyl 80 µg kg-1 hour-1, and three pigs at dexmedetomidine 8.0 µg kg-1 hour-1 had mechanical latencies greater than 60 seconds. Spontaneous EMG activity increased accompanied by visually evident 'shivering' at fentanyl 5, 10 and 20 µg kg-1 hour-1 but decreased at dexmedetomidine 2, 4 and 8 µg kg-1 hour-1. Clinically relevant effects of increasing infusion rates on blood pressure or pulse rate were not observed. CONCLUSION AND CLINICAL RELEVANCE: If anaesthetic plane or antinociception is evaluated in pigs, response to claw clamping and NWR will not necessarily give uniform results when comparing drugs. If only one method is used, results should be interpreted cautiously.

Plasma concentrations at two dexmedetomidine constant rate infusions in isoflurane anaesthetized horses: a clinical study.

OBJECTIVE: To determine dexmedetomidine plasma concentrations at two infusion rates in isoflurane anaesthetized horses and compare cardiovascular effects and anaesthetic recovery between treatments. STUDY DESIGN: Prospective, randomized, masked clinical study. ANIMALS: Healthy, adult, client-owned, non-food producing horses presented for castration. METHODS: Premedication consisted of acepromazine, romifidine and morphine, and anaesthesia was induced with ketamine and midazolam. The horses were randomized to receive dexmedetomidine 0.5 µg kg-1 hour-1 (treatment DL, n = 7) or 1.75 µg kg-1 hour-1 (treatment DH, n = 7) for 90 minutes of isoflurane anaesthesia at an end-tidal concentration of 1.2%. Venous plasma concentrations were determined with liquid chromatography-electrospray-ionization-tandem mass spectrometry. Jugular venous and arterial blood was sampled for blood gas analysis at the start and end of the infusion. Changes in cardiovascular variables from the start to the end of the infusion, and recovery parameters were statistically compared between treatments. RESULTS: Fourteen male horses, 2-6 years old, 325-536 kg were included. Mean ± standard deviation dexmedetomidine plasma concentrations at 30, 60 and 90 minutes with treatment DL were 0.22 ± 0.05, 0.29 ± 0.07 and 0.33 ± 0.08 ng mL-1, and with treatment DH were 0.65 ± 0.11, 0.89 ± 0.10 and 1.01 ± 0.10 ng mL-1. The 95% confidence interval for change minute-1 in dexmedetomidine plasma concentrations between 75 and 90 minutes was 0-1% for both treatments. With treatment DH, the heart rate decreased significantly more from the beginning to the end of the infusion compared to DL (p = 0.043). No other significant differences were found between treatments in cardiovascular or recovery parameters. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of dexmedetomidine in isoflurane anaesthetized horses resulted in plasma concentrations with low variation at both infusion rates, approaching stable levels after 75 minutes of infusion. No differences of clinical importance were found when comparing cardiovascular variables and quality of recovery between treatments.

Ex vivo characterization of particle transport in mucus secretions coating freshly excised mucosal tissues.

Sustained drug delivery to mucosal surfaces has the potential to improve the effectiveness of prophylactic and therapeutic treatments for numerous diseases and conditions, including inflammatory bowel disease, sexually transmitted diseases, cystic fibrosis, glaucoma, dry eye, and various cancers. Sustained delivery systems such as nanoparticles can be useful for mucosal delivery, but recent work suggests they must penetrate the rapidly cleared mucus barrier that overlies all mucosal epithelia to achieve uniform distribution on epithelial surfaces and enhanced residence time. Thus, it is important to evaluate the mucus-penetrating ability of nanosized delivery systems in preclinical animal studies, and for administration to humans. We describe a simple ex vivo method to visualize and quantify nanoparticle transport in mucus on fresh mucosal tissues. Using this method in murine models, we observed variations in the mucus mesh at different anatomical locations, as well as cyclical variations that may have implications for mucosal delivery.

High and Hyper: Fentanyl Induces Psychomotor Side-Effects in Healthy Pigs.

Analgesic effects of fentanyl have been investigated using behavior. The behavioral effects of fentanyl and possible serotonergic influence are largely unknown. We therefore investigated behavioral effects of fentanyl, with or without the serotonin antagonist ketanserin, in pigs. Fourteen mixed-breed pigs, weighing 17-25 kg were included in a randomised blinded prospective, balanced three-group study. Ten pigs received first 5 and then 10 µg/kg of fentanyl intravenously. Ketanserin at 1 mg/kg or saline was given intravenously as a third injection. Four control pigs received three injections of saline. Behavior was video-recorded. The distance moved was automatically measured by commercially available software, and behaviors manually scored in retrospect. Fentanyl inhibited resting and playing, and induced different repetitive behaviors. The mean (SD) distance moved in the control group and fentanyl group was 21.3 (13.0) and 57.8 (20.8) metres respectively (p < 0.05 for pairwise comparison). A stiff gait pattern was seen after fentanyl injection for median (range) 4.2 (2.8-5.1) minutes per 10 min, which was reduced to 0 (0-4) s after ketanserin administration. Conclusion: fentanyl-induced motor and behavioral effects, and serotonergic transmission may be involved in some of them. The psychomotor side effects of fentanyl could potentially interfere with post-operative pain evaluation in pigs.

CO2 Stunning in Pigs: Physiological Deviations at Onset of Excitatory Behaviour.

Stunning by carbon dioxide (CO2) inhalation is controversial because it is associated with vigorous movements and behaviours which may or may not be conscious reactions. Furthermore, it is unknown whether some behaviours might indicate the transition into unconsciousness. Our study objective was to investigate the loss of consciousness during CO2 stunning by linking physiological variables (in particular pH, PaO2 and PaCO2) to the onset of observed behaviours. A total of 11 cross-bred pigs were studied. A tracheostomy tube, venous and arterial cannulae were placed under sevoflurane anaesthesia. After recovery from this, and a "wash out" period of at least 30 min, arterial blood samples were taken (and baseline values established) before 90-95% CO2 in medical air was administered through the tracheostomy tube. Subsequent behaviours were video-recorded and key physiological variables were evaluated using an anaesthetic monitor and the frequent sampling of arterial blood (albeit with inconsistent inter-sample intervals). After the study, behaviours were classified in an ethogram. At the onset of behaviours categorised as "vigorous movement extremities", "opisthotonos" and "agonal gasping" pH values (range) were: 6.74-7.34; 6.66-6.96 and 6.65-6.87, while PaCO2 (kPa) was 4.6-42.2, 24.4-51.4 and 29.1-47.6. Based upon these values, we conclude that the pigs were probably unconscious at the onset of "opisthotonos" and "agonal gasping", but some were probably conscious at the onset of "vigorous movements".

Cardiovascular effects of intravenous morphine in anesthetized horse.

Objectives: To investigate whether morphine causes a change in mean arterial blood pressure (MAP) heart rate (HR) and oxygen extraction (OE) rate in healthy horses anesthetized with isoflurane and a dexmedetomidine infusion. Material and methods: The study design was prospective clinical, randomized, blinded two groups including 33 horses. All horses were sedated with romifidine IV, and anesthesia was induced with midazolam IV and ketamine IV and maintained with isoflurane in oxygen and medical air and a dexmedetomidine infusion. As a baseline venous and arterial blood, HR and MAP were sampled. Thereafter either morphine 0.1 mg kg-1 IV or an equivalent volume of NaCl 0.9% IV was administered. HR and MAP were then further sampled for 5 min before venous and arterial blood was again sampled. OE was calculated based upon arterial and venous blood gas analysis. To evaluate the change in minimum MAP, mean HR, and OE, the differences between baseline and observation period values were further termed delta MAP, delta HR, and delta OE. Individual delta MAPs were normalized to the minimum baseline value and are reported as a percentage. Alpha was set to 0.05. Confidence intervals 95% (CI) were calculated for delta MAP, delta HR, and delta OE within groups, and for the difference between groups. Results: The 95% CIs for delta MAP (%), delta HR (min-1), and delta OE (mL/dL) in the morphine group were -20.5 to -9.0, 0.6 to 3.1, and -0.1 to 0.6 and in the placebo group were -17.4 to -10.1, 0.2 to 2.0, and -0.2 to 0.3, respectively. The 95% CI for the differences in delta MAP (%), delta HR (min-1), and delta OE (mL/dL) were -5.5 to 7.6, -2.3 to 0.7, and -0.7 to 0.2, respectively. The minimum MAP of one horse in the morphine group decreased around 50% between baseline and observation period with almost unchanged OE and HR. Conclusion and clinical relevance: The effects of morphine 0.1 mg kg-1 IV on HR, MAP, and OE in healthy horses anesthetized with isoflurane and a CRI of dexmedetomidine are minimal.

Lidocaine spray 10% prior to intravenous catheterisation in dogs.

A common and to some degree painful procedure in veterinary practice is to insert an intra-venous catheter. In both human and veterinary medicine, a topical mixture of lidocaine and prilocaine (EMLA cream) has shown to reduce the pain, however a period of 60 min between application and initiation of the procedure is recommended. This time lapse is not always suitable for clinical practise and a shorter time before anaesthetic effect is therefore desirable. Lidocaine has a shorter time lapse (1-3 min) when used on mucus membrane; however, the effect of lidocaine for desensitization of skin has shown variable results in humans. The aim of the study was to evaluate the effect of topical lidocaine spray 10% on the response to placement of venous catheters in dogs. Topical lidocaine spray 10% or NaCl 0.9% was administered prior to placing an intravenous catheter in the cephalic vein. A cross-over of treatment with 2 h wash out period was used before placing a catheter in the opposite cephalic vein. The procedure was video recorded and the dogs' responses were later scored by three persons blinded to treatment using a visual analogue scale. The VAS scores were normalised and the mean difference between treatments were compared using Wilcox signed-rank test. This study could not find a statistical difference between the treatments (P = 0.1763) and could conclude that no significant difference in response to intravenous catheterisation was found between application of NaCl 0.9% or lidocaine 10% prior to the procedure.

Macrocirculatory Parameters and Oxygen Debt Indices in Pigs During Propofol Or Alfaxalone Anesthesia When Subjected to Experimental Stepwise Hemorrhage.

Background: Pigs are anesthetized when used for emergency procedures live tissue training (LTT) of civilian and military medical personnel or for experimental purposes, but there is a paucity in the literature regarding anesthesia of pigs for this purpose. Objective(s): The main goals of the study were to compare oxygen debt, macrocirculatory parameters, and time to cardiac arrest between pigs in hemorrhagic shock and anesthetized with propofol-ketamine-dexmedetomidine or alfaxalone-ketamine-dexmedetomidine. Design: A prospective, non-blinded randomized study design was used. Sixteen pigs were randomized in blocks of four to be anesthetized with either propofol-ketamine-dexmedetomidine (n = 8) or alfaxalone-ketamine-dexmedetomidine (n = 8) as a continuous infusion. Interventions: Premedication with ketamine 15 mg kg-1 and midazolam 1 mg kg-1 was given i.m. Anesthesia was maintained with propofol 8 mg kg-1 h-1 or alfaxalone 5 mg kg-1 h-1 combined with ketamine 5 mg kg-1 h-1 and dexmedetomidine 4 µg kg-1 h-1 i.v. A stepwise, volume-controlled model for hemorrhage was created by exsanguination. Main Outcome Measures: Indices of oxygen debt (lactate, base excess, and oxygen extraction), macrocirculatory (PR, SAP, DAP, MAP, and CI, SVI, and TPR) variables, and time to death was compared between groups. Results: Pigs in the alfaxalone group had significantly higher SAP than pigs given propofol. No difference in other macrocirculatory variables or indices of oxygen debt could be found. A blood loss of 50% of the total blood volume or more was possible in most pigs with both anesthetic regimes. Conclusions: Pigs anesthetized with propofol or alfaxalone combined with ketamine and dexmedetomidine tolerated substantial blood loss.

Pulmonary drug delivery: medicines for inhalation.

Mankind has inhaled substances for medical and other reasons for thousands of years, notably resulting in the cultural manifestations of tobacco and opium smoking. Over the course of time concepts of pulmonary application, including inhalation devices and drug formulations, have been and still are being continuously developed. State of the art instruments even allow for individualized drug application by adaptation of the inhalation procedure to the breathing pattern of the patient. Pulmonary drug delivery offers promising advantages in comparison to "classical" drug administration via the oral or transcutaneous routes, which is also reflected by an increasing interest and number of marketed products for inhalation therapy. However, the lungs' efficient clearance mechanisms still limit the benefit of many therapeutic concepts. In consequence the objective of current research and development in pulmonary drug delivery is to overcome and to control drug clearance from the intended target site. Here, several of the most auspicious future drug delivery concepts are presented and discussed in order to give the reader an insight into this emerging field of medicine.

A comparison of respiratory function in pigs anaesthetised by propofol or alfaxalone in combination with dexmedetomidine and ketamine.

BACKGROUND: General anaesthesia in pigs maintained with intravenous drugs such as propofol may cause respiratory depression. Alfaxalone gives less respiratory depression than propofol in some species. The aim of the investigation was to compare respiratory effects of propofol-ketamine-dexmedetomidine and alfaxalone-ketamine-dexmedetomidine in pigs. Sixteen pigs premedicated with ketamine 15 mg/kg and midazolam 1 mg/kg intramuscularly were anaesthetised with propofol or alfaxalone to allow endotracheal intubation, followed by propofol 8 mg/kg/h or alfaxalone 5 mg/kg/h in combination with ketamine 5 mg/kg/h and dexmedetomidine 4 µg/kg/h given as a continuous infusion for 60 min. The pigs breathed spontaneously with an FIO2 of 0.21. Oxygen saturation (SpO2), end-tidal CO2 concentration (PE'CO2), respiratory rate (fR) and inspired tidal volume (VT) were measured, and statistically compared between treatments. If the SpO2 dropped below 80% or if PE'CO2 increased above 10.0 kPa, the pigs were recorded as failing to complete the study, and time to failure was statistically compared between treatments. RESULTS: Alfaxalone treated pigs had significantly higher respiratory rates and lower PE'CO2 than propofol treated pigs, with a fR being 7.3 /min higher (P = 0.01) and PE'CO2 0.8 kPa lower (P = 0.05). SpO2 decreased by 0.6% and fR by 1.0 /min per kg increase in body weight in both treatment groups. Three of eight propofol treated and two of eight alfaxalone treated pigs failed to complete the study, and times to failure were not significantly different between treatments (P = 0.75). CONCLUSIONS: No major differences in respiratory variables were found when comparing treatments. Respiratory supportive measures must be available when using both protocols.

Chirality sensing with pores: reactive signal amplifiers for otherwise undetectable small molecules.

Recently, we have introduced a concept to determine enantiomeric excess (ee) with synthetic multifunctional pores (Tanaka and Matile, Chirality 2008;20:307-312). The reported approach is, however, limited to macromolecules and not applicable to small molecules. The problem is that the ability of synthetic pores to respond to chemical stimulation decreases with the size and the charge of the analyte. Here we demonstrate that this problem can be overcome with reactive signal amplifiers that covalently capture elusive analytes for sensitive recognition by the pore. For proof of principle, we use L-lactate and D-lactate as representative pair of enantiomers, L-lactate oxidase as stereospecific signal generator, and cascade blue hydrazide as reactive signal amplifier to capture the produced pyruvate. After stereospecific signal generation and reactive signal amplification, L-lactate was detectable quantitatively and without further optimization in the presence of at least 99% ee of D-lactate. Attempts to sense the traces of impurity in commercial samples of D-lactate gave values in the expected range (99.6% ee expected, 99.3 +/- 0.1% ee found).

Inhalative nanomedicine--opportunities and challenges.

Inhalation therapy is still limited by the low bioavailability of the administered drugs. Advantages of the pulmonary administration site like large resorption area, low enzymatic equipment, and circumvention of the first pass effect are set into perspective by the rigid barrier properties of the alveolar region. As a consequence, the systemic bioavailability of peptides and proteins is still relatively limited, even when administered by modern pharmaceutical aerosol technologies. In the context of advanced pulmonary drug therapy the use of nanoparticles as alternative to micronsized drug formulation could be of special interest, because nanoparticles seem to overcome some cellular barriers quite efficiently. Besides such outstanding permeation properties, nanoparticles may also hold promises to escape from pulmonary clearance mechanisms and to allow for cell-specific targeting within the lung. Such opportunities and challenges of inhalative nanomedicine are reviewed in this short review.

In-silico model of skin penetration based on experimentally determined input parameters. Part I: experimental determination of partition and diffusion coefficients.

Mathematical modeling of skin transport is considered a valuable alternative of in-vitro and in-vivo investigations especially considering ethical and economical questions. Mechanistic diffusion models describe skin transport by solving Fick's 2nd law of diffusion in time and space; however models relying entirely on a consistent experimental data set are missing. For a two-dimensional model membrane consisting of a biphasic stratum corneum (SC) and a homogeneous epidermal/dermal compartment (DSL) methods are presented to determine all relevant input parameters. The data were generated for flufenamic acid (M(W) 281.24g/mol; logK(Oct/H2O) 4.8; pK(a) 3.9) and caffeine (M(W) 194.2g/mol; logK(Oct/H2O) -0.083; pK(a) 1.39) using female abdominal skin. K(lip/don) (lipid-donor partition coefficient) was determined in equilibration experiments with human SC lipids. K(cor/lip) (corneocyte-lipid) and K(DSL/lip) (DSL-lipid) were derived from easily available experimental data, i.e. K(SC/don) (SC-donor), K(lip/don) and K(SC/DSL) (SC-DSL) considering realistic volume fractions of the lipid and corneocyte phases. Lipid and DSL diffusion coefficients D(lip) and D(DSL) were calculated based on steady state flux. The corneocyte diffusion coefficient D(cor) is not accessible experimentally and needs to be estimated by simulation. Based on these results time-dependent stratum corneum concentration-depth profiles were simulated and compared to experimental profiles in an accompanying study.

Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation.

Mucoadhesive particles (MAP) have been widely explored for pulmonary drug delivery because of their perceived benefits in improving particle residence in the lungs. However, retention of particles adhesively trapped in airway mucus may be limited by physiologic mucus clearance mechanisms. In contrast, particles that avoid mucoadhesion and have diameters smaller than mucus mesh spacings rapidly penetrate mucus layers [mucus-penetrating particles (MPP)], which we hypothesized would provide prolonged lung retention compared to MAP. We compared in vivo behaviors of variously sized, polystyrene-based MAP and MPP in the lungs following inhalation. MAP, regardless of particle size, were aggregated and poorly distributed throughout the airways, leading to rapid clearance from the lungs. Conversely, MPP as large as 300 nm exhibited uniform distribution and markedly enhanced retention compared to size-matched MAP. On the basis of these findings, we formulated biodegradable MPP (b-MPP) with an average diameter of <300 nm and examined their behavior following inhalation relative to similarly sized biodegradable MAP (b-MAP). Although b-MPP diffused rapidly through human airway mucus ex vivo, b-MAP did not. Rapid b-MPP movements in mucus ex vivo correlated to a more uniform distribution within the airways and enhanced lung retention time as compared to b-MAP. Furthermore, inhalation of b-MPP loaded with dexamethasone sodium phosphate (DP) significantly reduced inflammation in a mouse model of acute lung inflammation compared to both carrier-free DP and DP-loaded MAP. These studies provide a careful head-to-head comparison of MAP versus MPP following inhalation and challenge a long-standing dogma that favored the use of MAP for pulmonary drug delivery.

Effects of Mechanical Ventilation on Heart Geometry and Mitral Valve Leaflet Coaptation During Percutaneous Edge-to-Edge Mitral Valve Repair.

OBJECTIVES: This study sought to evaluate a ventilation maneuver to facilitate percutaneous edge-to-edge mitral valve repair (PMVR) and its effects on heart geometry. BACKGROUND: In patients with challenging anatomy, the application of PMVR is limited, potentially resulting in insufficient reduction of mitral regurgitation (MR) or clip detachment. Under general anesthesia, however, ventilation maneuvers can be used to facilitate PMVR. METHODS: A total of 50 consecutive patients undergoing PMVR were included. During mechanical ventilation, different levels of positive end-expiratory pressure (PEEP) were applied, and parameters of heart geometry were assessed using transesophageal echocardiography. RESULTS: We found that increased PEEP results in elevated central venous pressure. Specifically, central venous pressure increased from 14.0 ± 6.5 mm Hg (PEEP 3 mm Hg) to 19.3 ± 5.9 mm Hg (PEEP 20 mm Hg; p < 0.001). As a consequence, the reduced pre-load resulted in reduction of the left ventricular end-systolic diameter from 43.8 ± 10.7 mm (PEEP 3 mm Hg) to 39.9 ± 11.0 mm (PEEP 20 mm Hg; p < 0.001), mitral valve annulus anterior-posterior diameter from 32.4 ± 4.3 mm (PEEP 3 mm Hg) to 30.5 ± 4.4 mm (PEEP 20 mm Hg; p < 0.001), and the medio-lateral diameter from 35.4 ± 4.2 mm to 34.1 ± 3.9 mm (p = 0.002). In parallel, we observed a significant increase in leaflet coaptation length from 3.0 ± 0.8 mm (PEEP 3 mm Hg) to 5.4 ± 1.1 mm (PEEP 20 mm Hg; p < 0.001). The increase in coaptation length was more pronounced in MR with functional or mixed genesis. Importantly, a coaptation length >4.9 mm at PEEP of 10 mm Hg resulted in a significant reduction of PMVR procedure time (152 ± 49 min to 116 ± 26 min; p = 0.05). CONCLUSIONS: In this study, we describe a novel ventilation maneuver improving mitral valve coaptation length during the PMVR procedure, which facilitates clip positioning. Our observations could help to improve PMVR therapy and could make nonsurgical candidates accessible to PMVR therapy, particularly in challenging cases with functional MR.

Evaluation of the bispectral index as an indicator of degree of central nervous system depression in isoflurane-anesthetized horses.

OBJECTIVE: To determine whether the bispectral index (BIS) can be used as an indicator of degree of CNS depression in isoflurane-anesthetized horses. ANIMALS: 10 Standardbred and 6 Norwegian cold-blooded trotter stallions admitted for routine castration. PROCEDURE: A 2-channel referential electrode configuration was used to record EEG for calculation of BIS by the EEG monitor. The BIS was calculated before (awake) and after (sedated) administration of detomidine (0.01 mg/kg of body weight, IV) and butorphanol (0.01 mg/kg, IV). Anesthesia was induced with ketamine hydrochloride (2.5 mg/kg, IV) and diazepam (0.04 mg/kg, IV) and maintained with isoflurane delivered in oxygen. The BIS was calculated after 30 minutes of equilibration at an end-tidal isoflurane concentration of 1.4% (n = 8) or 1.9% (8) and recorded continuously during surgery. RESULTS: Bispectral index was significantly less in sedated and anesthetized horses, compared with awake horses. However, BIS was not significantly different between sedated and anesthetized horses. Mean BIS in horses anesthetized at 1.9% isoflurane was significantly greater, compared with horses anesthetized at an end-tidal concentration of 1.4%. Four horses in the 1.4% group moved during surgery, and BIS increased immediately prior to movement in 2 of these horses. CONCLUSIONS AND CLINICAL RELEVANCE: BIS is not a precise indicator of degree of CNS depression in isoflurane-anesthetized horses. Thus, determination of BIS may not be a useful technique for monitoring anesthetic depth in isoflurane-anesthetized horses.

Cardiac magnetic resonance imaging in patients undergoing percutaneous mitral valve repair with the MitraClip system.

BACKGROUND: Percutaneous mitral valve repair (MVR) with the MitraClip(®) system in patients with mitral regurgitation (MR) is known to reduce symptoms and to improve cardiac morphology and function. MitraClip has been approved for cardiac magnetic resonance imaging (MRI). To date, however, no systematic analysis exists on cardiac MRI in patients undergoing the MitraClip procedure. OBJECTIVE: The aim of this study was to (1) prove feasibility and robustness of cardiac MRI and (2) visualize effects of the procedure on cardiac morphology and function by cardiac MRI. METHODS: 27 consecutive patients (age 77.5 ± 7.6 years) with symptomatic moderate to severe MR undergoing the MitraClip(®) procedure were prospectively included. Cardiac MRI at 1.5 T was performed before and at 3 months after intervention. Cardiac morphology and function were evaluated using steady-state free precession (SSFP) cine sequences by assessment of left ventricular enddiastolic and endsystolic diameters (LVEDD, LVESD) and volumes (EDV, ESV), ejection fraction (LVEF) and stroke volume (SV), diameter of mitral annulus, and myocardial mass (MM). Planimetry of the left atrium (LA) was performed in identical slices in a four-chamber view. RESULTS: Around the clip an extinction artifact was observed which did not disturb the evaluation of cardiac morphology and function. At follow-up, we observed significant decreases of LVEDD (58.0 to 53.3 mm, p < 0.0001), EDV (167 to 159 mL, p = 0.0006) and ESV (101 to 89 mL, p < 0.0001), diameter of mitral annulus (41.4 to 37.9 mm, p < 0.0001), myocardial mass (148.4 to 144.5 g, p = 0.0004) and LA size (40.2 to 37.6 cm(2), p < 0.0001). LVEF improved (43.3 to 46.7 %, p = 0.0041). CONCLUSIONS: Cardiac MRI is feasible and robust in patients with MitraClips. The clinical benefit of a successful MitraClip intervention is paralleled by significant improvements of cardiac morphology and function which can be monitored and validated using MRI in clinical follow-up examinations.

Androstenone and testosterone levels and testicular morphology of Duroc boars related to estimated breeding value for androstenone.

Androstenone and testosterone levels in Duroc boars with an estimated breeding value for androstenone (EBV(androstenone)) were followed in the period from birth to sexual maturity. The breeding value for androstenone had been estimated based on androstenone levels in 1202 Duroc boars at an age of 24 weeks. Testosterone and androstenone levels in plasma were recorded in 19 boars at 1 week of age and in their 15 respective litter-siblings at 3 weeks of age. Between 12 and 27 weeks of age, plasma levels were recorded weekly in a third set of 16 litter-siblings. In the last group, histomorphology was performed at 12, 16, 20, and 27 weeks of age to determine sexual maturity status. The EBV(androstenone) was positively related to plasma androstenone in animals 12 to 27 weeks of age and to plasma testosterone levels in 1- and 3-week-old animals. The EBV(androstenone) was not related to testis morphology. The concentration of fat androstenone was positively correlated to the percentage of immature seminiferous tubules and negatively correlated to the percentage of mature seminiferous tubules at 20 weeks. Testosterone in plasma showed no relationship with testis morphology. Most individuals reached puberty at 20 weeks of age, which indicates that Duroc mature later than crossbred boars. The results indicated that breeding value based on the single trait boar taint parameter EBV(androstenone) was not related to testicular development.