A history of shoulder instability is more common in young patients undergoing total shoulder arthroplasty.

BACKGROUND: Previous studies have shown an association between shoulder instability and the development of glenohumeral arthritis leading to total shoulder arthroplasty (TSA). The primary goal of this study was to evaluate if a history of shoulder instability was more common in patients aged <50 years undergoing TSA. The secondary objective was to determine if a history of prior surgical stabilization is more common in patients aged <50 years undergoing TSA. METHODS: Using the military health system data repository (MDR) and the Military Analysis and Reporting Tool (M2), we identified 489 patients undergoing primary TSA from October 1, 2013, to May 1, 2020, within the Military Health System (MHS). Patients aged <50 years were matched 1:2 with patients aged ≥50 years based on sex, race, and military status, with the final study population comprising 240 patients who underwent primary TSA during the study period. Electronic medical records were examined, and factors showing univariate association (P < .2) were included in a binary logistic regression analysis to determine associations between demographic or clinical factors and TSA prior to age 50 years. RESULTS: The groups differed significantly in shoulder arthritis subtype, with the older group having significantly more primary osteoarthritis (78% vs. 51%, P < .001). The younger group had significantly more patients with a history of shoulder instability (48% vs. 12%, P < .001), prior ipsilateral shoulder surgery of any type (74% vs. 34%, P < .001), and prior ipsilateral shoulder stabilization surgery (31% vs. 5%, P < .001). In the resultant logistic regression model, a history of shoulder instability (OR 5.0, P < .001) and a history of any prior ipsilateral shoulder surgery (OR 3.5, P < .001) were associated with TSA prior to the age of 50 years. CONCLUSIONS: Shoulder instability is a risk factor for TSA before age 50 years. It is unclear how surgical stabilization influences the development of secondary glenohumeral arthritis in shoulder instability. Patients should be counseled that recurrent instability could lead to earlier TSA, regardless of whether surgical stabilization is performed.

The Cost of Stiffness After Total Knee Arthroplasty.

BACKGROUND: Stiffness after primary total knee arthroplasty (TKA) is debilitating and poorly understood. A heterogenous approach to the treatment is often utilized, including both nonoperative and operative treatment modalities. The purpose of this study was to examine the prevalence of treatments used between stiff and non-stiff TKA groups and their financial impact. METHODS: An observational cohort study was conducted using a large database. A total of 12,942 patients who underwent unilateral primary TKA from January 1, 2017, to December 31, 2017, were included. Stiffness after TKA was defined as manipulation under anesthesia and a diagnosis code of stiffness or ankylosis, and subsequent diagnosis and procedure codes were used to identify the prevalence and financial impact of multiple common treatment options. RESULTS: The prevalence of stiffness after TKA was 6.1%. Stiff patients were more likely to undergo physical therapy, medication, bracing, alternative treatment, clinic visits, and reoperation. Revision surgery was the most common reoperation in the stiff TKA group (7.6%). The incidence of both arthroscopy and revision surgery were higher in the stiff TKA population. Dual component revisions were costlier for patients who had stiff TKAs ($65,771 versus $48,287; P < .05). On average, patients who had stiffness after TKA endured costs from 1.5 to 7.5 times higher than the cost of their non-stiff counterparts during the 2 years following index TKA. CONCLUSION: Patients who have stiffness after primary TKA face significantly higher treatment costs for both operative and nonoperative treatments than patients who do not have stiffness.

Royal knifefish generate powerful suction feeding through large neurocranial elevation and high epaxial muscle power.

Suction feeding in ray-finned fishes involves powerful buccal cavity expansion to accelerate water and food into the mouth. Previous XROMM studies in largemouth bass (Micropterus salmoides), bluegill sunfish (Lepomis macrochirus) and channel catfish (Ictalurus punctatus) have shown that more than 90% of suction power in high performance strikes comes from the axial musculature. Thus, the shape of the axial muscles and skeleton may affect suction feeding mechanics. Royal knifefish (Chitala blanci) have an unusual postcranial morphology, with a ventrally flexed vertebral column and relatively large mass of epaxial muscle. Based on their body shape, we hypothesized that royal knifefish would generate high power strikes by utilizing large neurocranial elevation, vertebral column extension and epaxial shortening. As predicted, C. blanci generated high suction expansion power compared with the other three species studied to date (up to 160 W), which was achieved by increasing both the rate of volume change and the intraoral subambient pressure. The large epaxial muscle (25% of body mass) shortened at high velocities to produce large neurocranial elevation and vertebral extension (up to 41 deg, combined), as well as high muscle mass-specific power (up to 800 W kg-1). For the highest power strikes, axial muscles generated 95% of the power, and 64% of the axial muscle mass consisted of the epaxial muscles. The epaxial-dominated suction expansion of royal knifefish supports our hypothesis that postcranial morphology may be a strong predictor of suction feeding biomechanics.

Atypical Mutation in Neisseria gonorrhoeae 23S rRNA Associated with High-Level Azithromycin Resistance.

A2059G mutation in the 23S rRNA gene is the only reported mechanism conferring high-level azithromycin resistance (HL-AZMR) in Neisseria gonorrhoeae Through U.S. gonococcal antimicrobial resistance surveillance projects, we identified four HL-AZMR gonococcal isolates lacking this mutational genotype. Genetic analysis revealed an A2058G mutation of 23S rRNA alleles in all four isolates. In vitro selected gonococcal strains with homozygous A2058G recapitulated the HL-AZMR phenotype. Taken together, we postulate that the A2058G mutation confers HL-AZMR in N. gonorrhoeae.

Implementation and Evaluation of Gradient Strip Antimicrobial Susceptibility Testing in US Public Health Laboratories to Respond to Resistant Gonorrhea.

BACKGROUND: Gradient strip antimicrobial susceptibility testing using Etest is conducted by local public health jurisdictions participating in the Strengthening the US Response to Resistant Gonorrhea (SURRG) program to inform public health responses to resistant gonorrhea. Proficiency testing results across the participating laboratories were analyzed and a comparison of Etest with the agar dilution method was conducted. METHODS: Laboratories participating in SURRG performed Etest for azithromycin (AZM), cefixime (CFX), and ceftriaxone (CRO). Concurrence between minimum inhibitory concentrations (MICs) obtained with Etest versus the agar dilution method using corresponding isolates was defined as ±1 double dilution. Specific levels of reduced susceptibility were termed "alerts" and included isolates with the following MICs: ≥2.0 µg/mL (AZM), ≥0.25 µg/mL (CFX), and ≥0.125 µg/mL (CRO). Categorical (alert/nonalert) agreement was calculated for MICs determined using Etest and agar dilution methods. RESULTS: Strengthening the US Response to Resistant Gonorrhea laboratories had high proficiency testing scores (≥98%) and low levels of interlaboratory variations in MICs. The overall concurrence of MICs (essential agreement) determined using agar dilution, and Etest was 96% (CRO), 96% (CFX), and 95% (AZM). Depending on the antibiotic tested, between 27% and 66% of isolates with alert MICs determined by Etest also had alert MICs using the reference agar dilution methodology; however, most of these alert MICs were detected at threshold levels. CONCLUSIONS: This study demonstrates that MICs produced by SURRG laboratories using Etest have a high level of concurrence with agar dilution. Although confirmation of specific alert MICs varied, Etest facilities rapid detection and response to emerging resistant gonorrhea.

Fishes can use axial muscles as anchors or motors for powerful suction feeding.

Some fishes rely on large regions of the dorsal (epaxial) and ventral (hypaxial) body muscles to power suction feeding. Epaxial and hypaxial muscles are known to act as motors, powering rapid mouth expansion by shortening to elevate the neurocranium and retract the pectoral girdle, respectively. However, some species, like catfishes, use little cranial elevation. Are these fishes instead using the epaxial muscles to forcefully anchor the head, and if so, are they limited to lower-power strikes? We used X-ray imaging to measure epaxial and hypaxial length dynamics (fluoromicrometry) and associated skeletal motions (XROMM) during 24 suction feeding strikes from three channel catfish (Ictalurus punctatus). We also estimated the power required for suction feeding from oral pressure and dynamic endocast volume measurements. Cranial elevation relative to the body was small (<5 deg) and the epaxial muscles did not shorten during peak expansion power. In contrast, the hypaxial muscles consistently shortened by 4-8% to rotate the pectoral girdle 6-11 deg relative to the body. Despite only the hypaxial muscles generating power, catfish strikes were similar in power to those of other species, such as largemouth bass (Micropterus salmoides), that use epaxial and hypaxial muscles to power mouth expansion. These results show that the epaxial muscles are not used as motors in catfish, but suggest they position and stabilize the cranium while the hypaxial muscles power mouth expansion ventrally. Thus, axial muscles can serve fundamentally different mechanical roles in generating and controlling cranial motion during suction feeding in fishes.

Pectoral fin kinematics and motor patterns are shaped by fin ray mechanosensation during steady swimming in Scarus quoyi.

For many fish species, rhythmic movement of the pectoral fins, or forelimbs, drives locomotion. In terrestrial vertebrates, normal limb-based rhythmic gaits require ongoing modulation with limb mechanosensors. Given the complexity of the fluid environment and dexterity of fish swimming through it, we hypothesize that mechanosensory modulation is also critical to normal fin-based swimming. Here, we examined the role of sensory feedback from the pectoral fin rays and membrane on the neuromuscular control and kinematics of pectoral fin-based locomotion. Pectoral fin kinematics and electromyograms of the six major fin muscles of the parrotfish, Scarus quoyi, a high-performance pectoral fin swimmer, were recorded during steady swimming before and after bilateral transection of the sensory nerves extending into the rays and surrounding membrane. Alternating activity of antagonistic muscles was observed and drove the fin in a figure-of-eight fin stroke trajectory before and after nerve transection. After bilateral transections, pectoral fin rhythmicity remained the same or increased. Differences in fin kinematics with the loss of sensory feedback also included fin kinematics with a significantly more inclined stroke plane angle, an increased angular velocity and fin beat frequency, and a transition to the body-caudal fin gait at lower speeds. After transection, muscles were active over a larger proportion of the fin stroke, with overlapping activation of antagonistic muscles rarely observed in the trials of intact fish. The increased overlap of antagonistic muscle activity might stiffen the fin system in order to enhance control and stability in the absence of sensory feedback from the fin rays. These results indicate that fin ray sensation is not necessary to generate the underlying rhythm of fin movement, but contributes to the specification of pectoral fin motor pattern and movement during rhythmic swimming.

Channel catfish use higher coordination to capture prey than to swallow.

When animals move they must coordinate motion among multiple parts of the musculoskeletal system. Different behaviours exhibit different patterns of coordination, however, it remains unclear what general principles determine the coordination pattern for a particular behaviour. One hypothesis is that speed determines coordination patterns as a result of differences in voluntary versus involuntary control. An alternative hypothesis is that the nature of the behavioural task determines patterns of coordination. Suction-feeding fishes have highly kinetic skulls and must coordinate the motions of over a dozen skeletal elements to draw fluid and prey into the mouth. We used a dataset of intracranial motions at five cranial joints in channel catfish ( Ictalurus punctatus), collected using X-ray reconstruction of moving morphology, to test whether speed or task best explained patterns of coordination. We found that motions were significantly more coordinated (by 20-29%) during prey capture than during prey transport, supporting the hypothesis that the nature of the task determines coordination patterns. We found no significant difference in coordination between low- and high-speed motions. We speculate that capture is more coordinated to create a single fluid flow into the mouth while transport is less coordinated so that the cranial elements can independently generate multiple flows to reposition prey. Our results demonstrate the benefits of both higher and lower coordination in animal behaviours and the potential of motion analysis to elucidate motor tasks.

A mobility-based classification of closed kinematic chains in biomechanics and implications for motor control.

Closed kinematic chains (CKCs), links connected to form one or more closed loops, are used as simple models of musculoskeletal systems (e.g. the four-bar linkage). Previous applications of CKCs have primarily focused on biomechanical systems with rigid links and permanently closed chains, which results in constant mobility (the total degrees of freedom of a system). However, systems with non-rigid elements (e.g. ligaments and muscles) and that alternate between open and closed chains (e.g. standing on one foot versus two) can also be treated as CKCs with changing mobility. Given that, in general, systems that have fewer degrees of freedom are easier to control, what implications might such dynamic changes in mobility have for motor control? Here, I propose a CKC classification to explain the different ways in which mobility of musculoskeletal systems can change dynamically during behavior. This classification is based on the mobility formula, taking into account the number of loops in the CKC and the nature of the constituent joint mobilities. I apply this mobility-based classification to five biomechanical systems: the human lower limbs, the operculum-lower jaw mechanism of fishes, the upper beak rotation mechanism of birds, antagonistic muscles at the human ankle joint and the human jaw processing a food item. I discuss the implications of this classification, including that mobility itself may be dynamically manipulated to simplify motor control. The principal aim of this Commentary is to provide a framework for quantifying mobility across diverse musculoskeletal systems to evaluate its potentially key role in motor control.

The relationship between pectoral fin ray stiffness and swimming behavior in Labridae: insights into design, performance and ecology.

The functional capabilities of flexible, propulsive appendages are directly influenced by their mechanical properties. The fins of fishes have undergone extraordinary evolutionary diversification in structure and function, which raises questions of how fin mechanics relate to swimming behavior. In the fish family Labridae, pectoral fin swimming behavior ranges from rowing to flapping. Rowers are more maneuverable than flappers, but flappers generate greater thrust at high speeds and achieve greater mechanical efficiency at all speeds. Interspecific differences in hydrodynamic capability are largely dependent on fin kinematics and deformation, and are expected to correlate with fin stiffness. Here we examine fin ray stiffness in two closely related species that employ divergent swimming behaviors, the flapping Gomphosus varius and the rowing Halichoeres bivittatus To determine the spatial distribution of flexural stiffness across the fin, we performed three-point bending tests at the center of the proximal, middle and distal regions of four equally spaced fin rays. Pectoral fin ray flexural stiffness ranged from 0.0001 to 1.5109 µN m2, and the proximal regions of G. varius fin rays were nearly an order of magnitude stiffer than those of H. bivittatus In both species, fin ray flexural stiffness decreased exponentially along the proximodistal span of fin rays, and flexural stiffness decreased along the fin chord from the leading to the trailing edge. Furthermore, the proportion of fin area occupied by fin rays was significantly greater in G. varius than in H. bivittatus, suggesting that the proportion of fin ray to fin area contributes to differences in fin mechanics.

The opercular mouth-opening mechanism of largemouth bass functions as a 3D four-bar linkage with three degrees of freedom.

The planar, one degree of freedom (1-DoF) four-bar linkage is an important model for understanding the function, performance and evolution of numerous biomechanical systems. One such system is the opercular mechanism in fishes, which is thought to function like a four-bar linkage to depress the lower jaw. While anatomical and behavioral observations suggest some form of mechanical coupling, previous attempts to model the opercular mechanism as a planar four-bar have consistently produced poor model fits relative to observed kinematics. Using newly developed, open source mechanism fitting software, we fitted multiple three-dimensional (3D) four-bar models with varying DoF to in vivo kinematics in largemouth bass to test whether the opercular mechanism functions instead as a 3D four-bar with one or more DoF. We examined link position error, link rotation error and the ratio of output to input link rotation to identify a best-fit model at two different levels of variation: for each feeding strike and across all strikes from the same individual. A 3D, 3-DoF four-bar linkage was the best-fit model for the opercular mechanism, achieving link rotational errors of less than 5%. We also found that the opercular mechanism moves with multiple degrees of freedom at the level of each strike and across multiple strikes. These results suggest that active motor control may be needed to direct the force input to the mechanism by the axial muscles and achieve a particular mouth-opening trajectory. Our results also expand the versatility of four-bar models in simulating biomechanical systems and extend their utility beyond planar or single-DoF systems.

Increased Susceptibility to Atrial Fibrillation Secondary to Atrial Fibrosis in Transgenic Goats Expressing Transforming Growth Factor-ß1.

INTRODUCTION: Large animal models of progressive atrial fibrosis would provide an attractive platform to study relationship between structural and electrical remodeling in atrial fibrillation (AF). Here we established a new transgenic goat model of AF with cardiac specific overexpression of TGF-ß1 and investigated the changes in the cardiac structure and function leading to AF. METHODS AND RESULTS: Transgenic goats with cardiac specific overexpression of constitutively active TGF-ß1 were generated by somatic cell nuclear transfer. We examined myocardial tissue, ECGs, echocardiographic data, and AF susceptibility in transgenic and wild-type control goats. Transgenic goats exhibited significant increase in fibrosis and myocyte diameters in the atria compared to controls, but not in the ventricles. P-wave duration was significantly greater in transgenic animals starting at 12 months of age, but no significant chamber enlargement was detected, suggesting conduction slowing in the atria. Furthermore, this transgenic goat model exhibited a significant increase in AF vulnerability. Six of 8 transgenic goats (75%) were susceptible to AF induction and exhibited sustained AF (>2 minutes), whereas none of 6 controls displayed sustained AF (P < 0.01). Length of induced AF episodes was also significantly greater in the transgenic group compared to controls (687 ± 212.02 seconds vs. 2.50 ± 0.88 seconds, P < 0.0001), but no persistent or permanent AF was observed. CONCLUSION: A novel transgenic goat model with a substrate for AF was generated. In this model, cardiac overexpression of TGF-ß1 led to an increase in fibrosis and myocyte size in the atria, and to progressive P-wave prolongation. We suggest that these factors underlie increased AF susceptibility.

Pickleball Primer: An Overview of Common Injuries, Treatment, and Optimization Strategies in Pickleball Athlete.

Pickleball is one of the fastest growing sports in the United States with millions of players nationwide. It is a relatively appealing sport because of its ease of access, low impact, and highly social atmosphere, allowing players of all ages to participate. As the number of players continues its dramatic increase, player injuries are certain to increase in turn. There is little to no orthopaedic research on pickleball-related injuries and a paucity of data regarding treatment and prevention strategies. This summary was designed to familiarize orthopaedic surgeons with the basics of the sport and highlight potential pickleball-related injuries they may encounter in practice.

Correlation of Patient-Reported Preoperative Narcotic Use and Postoperative Requirements in Total Joint Arthroplasty.

Preoperative narcotic use is associated with diminished outcomes and increased complications in patients undergoing primary total joint arthroplasty (TJA). The goal of this study was to compare self-reported and state database identified preoperative narcotic use and correlate it with perioperative narcotic requirements in patients undergoing primary arthroplasty. A total of 788 patients undergoing unilateral TJA from a single institution were examined using self-reported preoperative narcotic use questionnaires and were verified using the Massachusetts Prescriber Awareness Tool (MassPAT). Demographic data, perioperative morphine milligram equivalents, and postdischarge refills were recorded and analyzed. Of the total population, 16.4% of patients undergoing TJA had verified MassPAT narcotics prescriptions preoperatively. Of these patients, 55% accurately reported use to their surgeon. Patients with verified MassPAT narcotic prescriptions required more morphine milligram equivalents than patients without MassPAT prescriptions, regardless of their preoperative self-report at all time points in the study. Patients who accurately reported use required more narcotics than those who did not. Patients with MassPAT prescriptions required more postdischarge refills than patients without MassPAT prescriptions. These data suggest that state-run narcotics databases may be more useful than self-reports for identifying which patients may require more opioids both immediately postoperatively and after hospital discharge. [Orthopedics. 2024;47(1):34-39.].

Disparities in Demographics in Hip Arthroplasty Between U.S. Active Duty Military and the ACS-NSQIP Clinical Registry.

INTRODUCTION: Patient demographics, such as sex and age, are known risk factors for undergoing revision following primary total hip arthroplasty (THA). The military population is unique because of the increased rates of primary and secondary osteoarthritis of the hip. Treatment options are limited for returning patients to their line of duty; however, THA has been shown to be an effective option. The primary purpose of this study was to evaluate and contrast the demographic differences of patients undergoing primary THA between the U.S. active duty military population and the general population. The secondary goal was to identify the proportion of primary THA performed at the MTF within the military health system (MHS). METHODS: This was an exempt study determined by the local institutional review board. A retrospective analysis of the MHS Data Repository (MDR) and the National Surgical Quality Improvement Program (NSQIP) was performed. The databases were used to identify the patients who underwent THA from January 1, 2015 to December 31, 2020. The MDR was used to identify demographics such as sex, age, setting of surgery, geographic location, previous military deployments, history of deployment-related injuries, branch of service, and rank. The NSQIP database was queried for sex and age. The median age of the population was compared using the Mann-Whitney U test and gender was compared using the Chi-square test. RESULTS: The MDR was used to evaluate 2,734 patients, whereas the NSQIP database was used to evaluate 223,832 patients. In the military population, patients who underwent THA were 87.7% male with an average age of 45 years, whereas in the general population as measured via the NSQIP database, 45.2% patients were male with an average age of 66.0 years. Comparing the two groups, we demonstrated that the military patients were significantly more likely to be younger (P < .001) and males (P < .001). Only 29.6% of primary THAs were performed within the MTF. CONCLUSIONS: Patients in the MHS are undergoing THA at a younger age and are more likely to be male compared to the general population. A significant portion of primary THAs in the MHS are also being performed at civilian institutions. These demographics may result in increased risk of revision; however, long-term studies are warranted to evaluate survivorship in this unique population.

Similar incidence of postoperative sciatic nerve palsy in direct anterior and posterior approach total hip arthroplasty.

BACKGROUND: Sciatic nerve palsy is a rare but devastating complication following total hip arthroplasty (THA). While the use of the direct anterior approach is increasing, limited data exist regarding sciatic nerve palsy and surgical approach. The purpose of this study was to determine the factors and outcomes associated with sciatic nerve palsy (SNP) after THA. METHODS: A retrospective analysis was performed at a single institution of 7 SNP that occurred in 4045 THA via direct anterior approach and 10 SNP in 8854 THA via posterior approach, being operated between 01 January 2017 and 12 December 2021. SNP patients were matched 1:5 to patients without SNP. Medical records were reviewed for demographics including age, gender, body mass index (BMI), comorbidities, and preoperative indication. Additional workup of SNP patients including advanced imaging and reoperation were documented. Recovery grades were assigned to all SNP patients at most recent clinical follow-up. RESULTS: 5 of the SNP were complete and 12 partial. They occurred as frequently with the direct anterior (0.17%) and posterior approach (0.11%, p = 0.5). The presence of femur cables and reoperations were associated with SNP (p = 0.04 and p = 0.002, respecitvely). Age, gender, BMI, comorbidities, and surgical indication had no effect on SNP. 4 of the 17 affected patients had almost complete recovery at latest follow-up. CONCLUSIONS: The incidence of SNP was similar in direct anterior and posterior approach. Surgeons should counsel patients regarding the risks of SNP regardless of the used approach.

Detection of Traumatic Ankle Arthrotomies: Computed Tomography Scan Versus Saline Load Test.

OBJECTIVE: Periarticular wounds present a common diagnostic dilemma for emergency providers and orthopedic surgeons because traumatic arthrotomies (TA) often necessitate different management from superficial soft tissue wounds. Historically, TA have been diagnosed with the saline load test (SLT). Computed tomography (CT) scan has been studied as an alternative to SLT in diagnosing TA in several joints, but there are limited data specifically pertaining to the ankle. This study aimed to compare the ability of a CT scan to identify an ankle TA versus a traditional SLT. The hypothesis was that there would be no significant difference between a CT scan and SLT in diagnosing ankle TA in a cadaveric model. METHODS: This cadaveric study used 10 thawed fresh-frozen cadaveric ankles. A baseline CT scan was performed to ensure no intra-articular air existed before simulated TA. After the baseline CT, a 1 cm TA was created in the anterolateral arthroscopy portal site location. The ankles then underwent a postarthrotomy CT scan to evaluate for the presence of intra-articular air. After the CT scan, a 30 mL SLT was performed using the anteromedial portal site location. RESULTS: After arthrotomy, intra-articular air was visualized in 7 of 10 cadavers in the postarthrotomy CT scan. All the ankles had fluid extravasation during the SLT with <10 mL of saline. The sensitivity of the SLT for TA was 100% versus 70% for the CT scan. CONCLUSIONS: The SLT was more sensitive in diagnosing 1-cm ankle TA than a CT scan in a cadaveric model.

Binding Affinity, Selectivity, and Pharmacokinetics of the Oxytocin Receptor Antagonist L-368,899 in the Coyote (Canis latrans).

L-368,899 is a selective small-molecule oxytocin receptor (OXTR) antagonist originally developed in the 1990s to prevent preterm labor. Although its utility for that purpose was limited, L-368,899 is now one of the most commonly used drugs in animal research for the selective blockade of neural OXTR after peripheral delivery. A growing number of rodent and primate studies have used L-368,899 to evaluate whether certain behaviors are oxytocin dependent. These studies have improved our understanding of oxytocin's function in the brains of rodents and monkeys, but very little work has been done in other mammals, and only a single paper in macaques has provided any evidence that L-368,899 can be detected in the CNS after peripheral delivery. The current study sought to extend those findings in a novel species: coyotes ( Canis latrans ). Coyotes are ubiquitous North American canids that form long-term monogamous pair-bonds. Although monogamy is rare in rodents and primates, all wild canid species studied to date exhibit social monogamy. Coyotes are therefore an excellent model organism for the study of oxytocin and social bonds. Our goal was to determine whether L-368,899 is a viable candidate for future use in behavioral studies in coyotes. We used captive coyotes at the USDA National Wildlife Research Center's Predator Research Facility to evaluate the pharmacokinetics of L-368,899 in blood and CSF during a 90-min time course after intramuscular injection. We then characterized the binding affinity and selectivity of L-368,899 to coyote OXTR and the structurally similar vasopressin 1a receptor. We found that L-368,899 peaked in CSF at 15 to 30 min after intramuscular injection and slowly accumulated in blood. L-368,899 was 40 times more selective for OXTR than vasopressin 1a receptors and bound to the coyote OXTR with an affinity of 12 nM. These features of L-368,899 support its utility in future studies to probe the oxytocin system of coyotes.

Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs.

Structural remodeling in chronic atrial fibrillation (AF) occurs over weeks to months. To study the electrophysiological, structural, and functional changes that occur in chronic AF, the selection of the best animal model is critical. AF was induced by rapid atrial pacing (50-Hz stimulation every other second) in pigs (n = 4), dogs (n = 8), and goats (n = 9). Animals underwent MRIs at baseline and 6 mo to evaluate left ventricular (LV) ejection fraction (EF). Dogs were given metoprolol (50-100 mg po bid) and digoxin (0.0625-0.125 mg po bid) to limit the ventricular response rate to <180 beats/min and to mitigate the effects of heart failure. The pacing leads in pigs became entirely encapsulated and lost the ability to excite the heart, often before the onset of sustained AF. LV EF in dogs dropped from 54 ± 11% at baseline to 33 ± 7% at 6 mo (P < 0.05), whereas LV EF in goats did not drop significantly (69 ± 8% at baseline vs. 60 ± 9% at 6 mo, P = not significant). After 6 mo of AF, fibrosis levels in dog atria and ventricles increased, whereas only atrial fibrosis levels increased in goats compared with control animals. In our experience, the pig model is not appropriate for chronic rapid atrial pacing-induced AF studies. Rate-controlled chronic AF in the dog model developed HF and LV fibrosis, whereas the goat model developed only atrial fibrosis without ventricular dysfunction and fibrosis. Both the dog and goat models are representative of segments of the patient population with chronic AF.