Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus).

The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days -1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain.

Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus).

Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

Evaluation of Isoflurane Overdose for Euthanasia of Neonatal Mice.

Neonatal mice (that is, pups younger than 6 d) must be exposed to CO2 for as long as 50 min to achieve euthanasia. Alternatively, other inhalant anesthetic agents have been used to euthanize laboratory rodent species. We investigated the efficacy of isoflurane at saturated vapor pressure to euthanize neonatal mice. Neonatal mice (n = 76; age, 1 or 2 d) were exposed to isoflurane in a sealed, quart-size (0.95-L) plastic bag at room temperature. Righting and withdrawal reflexes were absent in less than 2 min. After 30 min of exposure to isoflurane, pups were removed and monitored for recovery. All pups were cyanotic and showed no detectable signs of life when they were removed from the bag. However, after 30 to 120 min after removal from the bag, 24% of isoflurane-overexposed pups began gasping and then resumed normal respiration and regained a normal pink coloration. These results demonstrate that isoflurane overexposure at saturated vapor pressure for 30 min is insufficient to euthanize neonatal mice and that isoflurane overexposure must be followed by a secondary means of euthanasia.

Combining blink, pupil, and response time measures in a concealed knowledge test.

The response time (RT) based Concealed Knowledge Test (CKT) has been shown to accurately detect participants' knowledge of mock-crime-related information. Tests based on ocular measures such as pupil-size and blink-rate have sometimes resulted in poor classification, or lacked detailed classification analyses. The present study examines the fitness of multiple pupil and blink related responses in the CKT paradigm. To maximize classification efficiency, participants' concealed knowledge was assessed using both individual test measures and combinations of test measures. Results show that individual pupil-size, pupil-slope, and pre-response blink-rate measures produce efficient classifications. Combining pupil and blink measures yielded more accuracy classifications than individual ocular measures. Although RT-based tests proved efficient, combining RT with ocular measures had little incremental benefit. It is argued that covertly assessing ocular measures during RT-based tests may guard against effective countermeasure use in applied settings. A compound classification procedure was used to categorize individual participants and yielded high hit rates and low false-alarm rates without the need for adjustments between test paradigms and subject populations. We conclude that with appropriate test paradigms and classification analyses, ocular measures may prove as effective as other indices, though additional research is needed.

Brain activation evidence for response conflict in the exclude recognition task.

How do memory retrieval processes (i.e., familiarity and recollection processes) interact with motor and control processes to bring about an appropriate response? Our parallel task-set model predicts, and behavioral and electromyographic data support, the hypothesis that under some circumstances familiarity and recollection processes activate competing responses. Combining predictions from the parallel task-set model and the conflict monitoring hypothesis, this competition should lead to response conflict and corresponding activity in anterior cingulate cortex (ACC). However, ACC activity in response to competing familiarity and recollection retrieval processes is inconsistently reported in the literature. We tested this prediction directly by measuring brain activation with functional magnetic resonance imaging while participants performed an exclude recognition task (i.e., respond one way to one set of familiar stimuli and another way to new and to a different set of familiar stimuli). As predicted by our model, overriding a familiarity-based response led to increased activity in ACC. These data suggest that recognition, motor, and control processes interact in strategic retrieval tasks.

Relief of branch pulmonary artery stenosis reduces pulmonary valve insufficiency in a swine model.

OBJECTIVE: We sought to determine the impact of relieving branch pulmonary artery stenosis on pulmonary valve insufficiency and right ventricular function. Long-standing pulmonary insufficiency causes progressive right ventricular dilatation, leading to decreased right ventricular function. Adults with pulmonary insufficiency are at risk of decreased exercise tolerance, arrhythmias, and sudden cardiac death. Branch pulmonary artery stenosis frequently occurs in these patients, and the presence of branch stenosis may exacerbate valve insufficiency. METHODS: Neonatal piglets (n = 7) underwent surgery to create pulmonary insufficiency and left pulmonary artery stenosis. At 3 months of age, the animals underwent baseline cardiac magnetic resonance imaging followed by stenting of the left pulmonary artery. A repeat magnetic resonance imaging scan was performed 1 week after intervention. Magnetic resonance imaging evaluation included (1) velocity mapping to assess the forward and reverse flow at the main, left and right pulmonary arteries, and aorta; and (2) volumetric assessment of the right ventricle. RESULTS: Left pulmonary artery flow increased from 14.5% to 36.3% of total net flow after stenting (P < .01). Pulmonary regurgitation decreased from 38.7% to 27.4% (P < .02). Right ventricular ejection fraction improved from a median of 53.5% to 58.2% after stenting (P < .01). Cardiac index improved from a median of 2.7 to 3.5 L/min/m(2) (P = .01). CONCLUSION: Relief of branch pulmonary artery stenosis reduces insufficiency and improves right ventricular systolic function in this animal model. This supports the practice of aggressive intervention in patients with branch pulmonary artery stenosis and pulmonary insufficiency.

Time and encoding effects in the concealed knowledge test.

Although the traditional "lie detector" test is used frequently in forensic contexts, it has (like most test of deception) some limitations. The concealed knowledge test (CKT) focuses on participants' recognition of privileged knowledge rather than lying per-se and has been studied extensively using a variety of measures. A "guilty" suspect's interaction with and memory of crimescene items may vary. Furthermore, memory for crimescene items may diminish over time. The interaction of encoding quality and test delay on CKT efficiency has been previously implied, but not yet demonstrated. We used a response-time based CKT to detect concealed knowledge from shallow and deep study procedures after 10-min, 24-h, and 1-week delays. Results show that more elaborately encoded information afforded higher detection accuracy than poorly encoded items. Although classification accuracy following deep study was unaffected by delay, detection of poorly elaborated information was initially high, but compromised after 1 week. Thus, choosing optimal test items requires considering both test delay and initial encoding level.

Electromyographic evidence for response conflict in the exclude recognition task.

How do memory retrieval processes lead to overt responses in strategic recognition tasks (responding "old" to one class of familiar stimulus and "new" to another)? Many current theories of memory retrieval ignore the response requirements in such memory tasks, instead modeling them using memory processes (e.g., familiarity and recollection) alone (see Yonelinas, 2002). We argue that strategic recognition involves conflict in response processing similar to canonical conflict tasks (e.g., the Stroop task). The parallel task set (PTS) model (Seymour, 2001) accounts for performance in strategic recognition tasks (e.g., the exclude recognition task) by suggesting that motor response conflict occurs when one responds "new" to familiar stimuli. We tested this prediction using surface electromyography, a measure incontrovertibly related to motor execution. Overall, results are consistent with the PTS model's assumption that recognition, motor, and control processes interact in strategic retrieval tasks. The implications of these data for models of memory retrieval and response conflict are discussed.

Aging and goal-directed emotional attention: distraction reverses emotional biases.

Previous findings reveal that older adults favor positive over negative stimuli in both memory and attention (for a review, see Mather & Carstensen, 2005). This study used eye tracking to investigate the role of cognitive control in older adults' selective visual attention. Younger and older adults viewed emotional-neutral and emotional-emotional pairs of faces and pictures while their gaze patterns were recorded under full or divided attention conditions. Replicating previous eye-tracking findings, older adults allocated less of their visual attention to negative stimuli in negative-neutral stimulus pairings in the full attention condition than younger adults did. However, as predicted by a cognitive-control-based account of the positivity effect in older adults' information processing tendencies (Mather & Knight, 2005), older adults' tendency to avoid negative stimuli was reversed in the divided attention condition. Compared with younger adults, older adults' limited attentional resources were more likely to be drawn to negative stimuli when they were distracted. These findings indicate that emotional goals can have unintended consequences when cognitive control mechanisms are not fully available.

Theoretical implications of articulatory duration, phonological similarity, and phonological complexity in verbal working memory.

The phonological-loop model provides a prominent theoretical description of verbal working memory. According to it, serial recall accuracy should be inversely related to the articulatory duration and phonological similarity of verbal items in memorized sequences. Initial tests of these predictions by A. D. Baddeley and colleagues (e.g., A. D. Baddeley, N. Thomson, & M. Buchanan, 1975) appeared to support the phonological-loop model, but subsequent researchers have obtained conflicting data that putatively disconfirm its assumptions. Such conflicts may have stemmed from less than ideal measurements of articulatory duration and phonological similarity. This article discusses these concerns and proposes new theoretically principled methods for measuring articulatory duration and phonological similarity. Two experiments that used these methods in the context of a verbal serial recall task are reported. The results of these experiments confirm and extend the predictions of the phonological-loop model while disarming previous criticisms of it.