Sugammadex for reversal of rocuronium-induced neuromuscular blockade during alfaxalone anesthesia in dogs.

OBJECTIVE: To investigate the reversal effect of sugammadex on neuromuscular blockade induced by a single bolus of rocuronium in dogs under alfaxalone anesthesia. STUDY DESIGN: Randomized, prospective, crossover experimental study. ANIMALS: A group of six adult Beagle dogs (three females and three males), weighing 11.3-15.8 kg and aged 6-8 years, were used. METHODS: Dogs were anesthetized twice with a 1.25 times minimum infusion rate of alfaxalone, with a washout period of at least 14 days between experiments. Neuromuscular function was monitored using acceleromyography with train-of-four (TOF) stimulation of the peroneal nerve. After recording the control TOF ratio (TOFRC), rocuronium (0.5 mg kg-1) was administered intravenously. Subsequently, sugammadex (4 mg kg-1) or an equal volume of saline (control treatment) was administered intravenously when the TOF count returned from 0 to 1 after neuromuscular blockade. Time from rocuronium injection to TOF count = 0 (onset time), time from TOF count = 0 to TOF count = 1 (maximum blockade period), time of first twitch amplitude recovery from 0.25 to 0.75 (recovery index), and time from sugammadex or saline administration to TOF ratio/TOFRC ≥ 0.9 (recovery time) were recorded. RESULTS: The onset time and maximum blockade duration did not differ between sugammadex treatment [1.2 (0.7-1.5) minutes and 9.9 (6.3-10.5) minutes, respectively] and control treatment [median (range); 1.0 (0.7-1.1) minutes and 9.9 (8.8-11.5) minutes, respectively] (p = 0.219 and 0.844, respectively). Recovery index was 0.5 (0.3-0.7) minutes in sugammadex treatment, which was shorter than that in control treatment [4.5 (3.7-4.9) minutes] (p = 0.031). Recovery time was 0.8 (0.5-2.8) minutes in sugammadex treatment, which was shorter than that in control treatment [10.5 (6.8-14.3) minutes] (p = 0.031). CONCLUSIONS AND CLINICAL RELEVANCE: Rocuronium-induced neuromuscular blockade was effectively reversed by sugammadex in dogs anesthetized with alfaxalone.

The sedative effect of intranasal administration of medetomidine using a mucosal atomization device in Japanese White rabbits.

To prevent aspiration in Japanese White (JW) rabbits, the maximum single volume of medetomidine administered intranasally is 0.3 mL per nostril using a mucosal atomization device (MAD). This study aimed to examine the sedative effect of intranasal administration of medetomidine using MAD in eight healthy female JW rabbits. Each rabbit received intranasal atomization (INA) of saline (Control treatment) along with three doses of 1 mg/mL medetomidine (0.3 mL to one nostril [MED0.3 treatment]; 0.3 mL each to both nostrils [MED0.6 treatment]; 0.3 mL twice to both nostrils [MED1.2 treatment]), with a washout period of at least 7 days between treatments. The actual doses of medetomidine were 82 (75-84) µg/kg (median [25th-75th percentile]), 163 (156-168) µg/kg, and 323 (295-343) µg/kg for the MED0.3, MED0.6, and MED1.2 treatments, respectively. A medetomidine-dose dependent sedative effect was detected, and the loss of righting reflex (LRR) was achieved in one rabbit at 18 min, seven rabbits at 11 (9-18) min, and eight rabbits at 7 (4-18) min after the MED0.3, MED0.6, and MED1.2 treatments, respectively. The LRR was maintained for 63 (29-71) min and 83 (68-101) min after the MED0.6 and MED1.2 treatments, respectively. Additionally, the INA of medetomidine produced a significant dose-dependent cardiorespiratory depression including a decrease in pulse rate, respiratory rate, percutaneous oxygen saturation, and arterial partial pressure of oxygen, and an increase in arterial partial pressure of carbon dioxide in the rabbits.

ED50 and ED95 of rocuronium during alfaxalone anesthesia in dogs.

OBJECTIVE: To determine the median effective dose (ED50) and effective dose required to depress the twitch value by 95% (ED95) of rocuronium during alfaxalone anesthesia in dogs. STUDY DESIGN: A randomized, prospective, crossover experimental study. ANIMALS: A total of eight adult Beagle dogs (four female, four male), weighing 10.3-14.6 kg and aged 6-8 years. METHODS: The dogs were anesthetized three times with 1.25-fold the individual minimum infusion rate of alfaxalone at intervals of ≥ 14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC) and first twitch of TOF (T1C), a single bolus dose of rocuronium 100, 175 or 250 µg kg-1 (treatments R100, R175 or R250) was administered intravenously. The maximum suppression of the first twitch of TOF (T1) was recorded and calibrated with T1C to construct the dose-response curve, from which ED50 and ED95 were calculated. Time from rocuronium administration to TOF ratio/TOFRC > 0.9 (duration TOFR0.9) was recorded. RESULTS: ED50 and ED95 of rocuronium during alfaxalone anesthesia were 175 and 232 µg kg-1, respectively. The median (range) duration TOFR0.9 was longer in treatment R250 [10.1 (9.2-10.9) minutes] than in treatments R100 [3.1 (2.9-4.4) minutes; p < 0.0001] and R175 [7.7 (6.9-8.1) minutes; p < 0.0001]; and longer in treatment R175 than in treatment R100 (p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: The duration of TOFR0.9 correlated positively with the dosage of rocuronium, indicating that recovery time of rocuronium was also dose-dependent in dogs anesthetized with alfaxalone. The duration TOFR0.9 of rocuronium 250 µg kg-1 was 10 minutes during alfaxalone anesthesia in dogs.

Sedative and cardiorespiratory effects of intranasal atomized alfaxalone in Japanese White rabbits.

OBJECTIVE: To investigate the sedative and cardiorespiratory effects of intranasal atomization (INA) of alfaxalone using a mucosal atomization device in Japanese White rabbits. STUDY DESIGN: Randomized, prospective, crossover study. ANIMALS: A total of eight healthy female rabbits, weighing 3.6-4.3 kg and aged 12-24 months. METHODS: Each rabbit was randomly assigned to four INA treatments administered 7 days apart: Control treatment, 0.15 mL 0.9% saline in both nostrils; treatment INA0.3, 0.15 mL 4% alfaxalone in both nostrils; treatment INA0.6, 0.3 mL 4% alfaxalone in both nostrils; treatment INA0.9, 0.3 mL 4% alfaxalone in left, then right, then left nostril. Sedation was scored 0-13 using a composite measure scoring system for rabbits. Simultaneously, pulse rate (PR), respiratory rate (fR), noninvasive mean arterial pressure (MAP), peripheral hemoglobin oxygen saturation (SpO2) and arterial blood gases were measured until 120 minutes. The rabbits breathed room air during the experiment and were administered flow-by oxygen when hypoxemia (SpO2 <90% or PaO2 <60 mmHg; 8.0 kPa) developed. Data were analyzed using the Fisher's exact test and the Friedman test (p < 0.05). RESULTS: No rabbit was sedated in treatments Control and INA0.3. All rabbits in treatment INA0.9 developed loss of righting reflex for 15 (10-20) minutes [median (25th-75th percentile)]. Sedation score significantly increased from 5 to 30 minutes in treatments INA0.6 and INA0.9 with maximum scores of 2 (1-4) and 9 (9-9), respectively. fR decreased in an alfaxalone dose-dependent manner and one rabbit developed hypoxemia in treatment INA0.9. No significant changes were observed in PR and MAP. CONCLUSIONS AND CLINICAL RELEVANCE: INA alfaxalone resulted in dose-dependent sedation and respiratory depression in Japanese White rabbits to values considered not clinically relevant. Further investigation of INA alfaxalone in combination with other drugs is warranted.

Maximum volume of nasal administration using a mucosal atomization device without aspiration in Japanese White rabbits.

Recently, a mucosal atomization device (MAD) has been applied in veterinary medicine. In the present study, the maximum volume of nasal atomization without aspiration using MAD was examined in eight healthy female Japanese White (JW) rabbits. Each rabbit had their head and neck examined by computed tomography before and after nasal atomization with four different doses (0.15, 0.3, 0.45, and 0.6 ml per nostril) of diluted contrast medium (1:2 mixture of iohexol and saline). This was done under general anesthesia by an intramuscular administration of alfaxalone 2.5 mg/kg, medetomidine 40 µg/kg, and butorphanol 0.4 mg/kg, with a 7-day washout period between each treatment. The diluted contrast medium was distributed in the nasal cavity, external nares, and/or oral cavity in all rabbits receiving each treatment. The intranasal distribution volumes of the contrast medium were 287 (250-333) mm3 [median (interquartile range)] for 0.15 ml, 433 (243-555) mm3 for 0.3 ml, 552 (356-797) mm3 for 0.45 ml, and 529 (356-722) mm3 for 0.6 ml of treatment. The intranasal distribution volume for 0.15 ml treatment tended to be lower than that for 0.6 ml treatment (P=0.083). The contrast medium was deposited in the trachea in one rabbit (12.5%) and four rabbits (50%) receiving treatments of 0.45 and 0.6 ml per nostril, respectively. The maximum volume of nasal atomization without aspiration into the trachea was 0.3 ml per nostril for the JW rabbits.

Effects of sevoflurane, propofol or alfaxalone on neuromuscular blockade produced by a single intravenous bolus of rocuronium in dogs.

OBJECTIVE: To compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs. STUDY DESIGN: A randomized, prospective, crossover experimental study. ANIMALS: A total of eight adult Beagle dogs (four female, four male), weighing 8.9-15.3 kg and aged 5-7 years. METHODS: The dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg-1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded. RESULTS: The onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0-30.3) minutes] than in PROP [16.6 (15.4-18.0) minutes; p = 0.002] and ALFX [22.4 (18.6-23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p < 0.001) and ALFX (32.5 ± 8.4 minutes; p = 0.036) treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.

A New Photographic Reproduction Method Based on Feature Fusion and Virtual Combined Histogram Equalization.

A desirable photographic reproduction method should have the ability to compress high-dynamic-range images to low-dynamic-range displays that faithfully preserve all visual information. However, during the compression process, most reproduction methods face challenges in striking a balance between maintaining global contrast and retaining majority of local details in a real-world scene. To address this problem, this study proposes a new photographic reproduction method that can smoothly take global and local features into account. First, a highlight/shadow region detection scheme is used to obtain prior information to generate a weight map. Second, a mutually hybrid histogram analysis is performed to extract global/local features in parallel. Third, we propose a feature fusion scheme to construct the virtual combined histogram, which is achieved by adaptively fusing global/local features through the use of Gaussian mixtures according to the weight map. Finally, the virtual combined histogram is used to formulate the pixel-wise mapping function. As both global and local features are simultaneously considered, the output image has a natural and visually pleasing appearance. The experimental results demonstrated the effectiveness of the proposed method and the superiority over other seven state-of-the-art methods.

Comparison of the neuromuscular blocking effects of cisatracurium during isoflurane or propofol anesthesia in dogs.

OBJECTIVE: To compare the neuromuscular blocking effects of cisatracurium during isoflurane versus propofol anesthesia in dogs. STUDY DESIGN: Prospective, randomized study. ANIMALS: A total of 20 healthy, client-owned dogs (16 females, four males) weighing 12.5-22 kg and aged 1-8 years. METHODS: Dogs undergoing elective surgery were randomized in equal numbers to an isoflurane (ISO) or propofol (PPF) group. Other drugs used during anesthesia were equal between groups. Single-twitch (ST) stimulation was used to monitor neuromuscular response. After recording the baseline ST (T0), cumulative doses of cisatracurium (0.05 mg kg-1) were administered intravenously until ST/T0 ≤5%. Effective doses 50 (ED50) and 95 (ED95) of cisatracurium in each group were calculated from group dose-response curves. Recovery of ST (TR) was defined as spontaneous recovery of ST to 80-120% of T0 remaining stable for 2 minutes. The ST after each dose of cisatracurium, duration 25% (time after the last dose until 25% recovery of TR), recovery index (time to recovery from 25% to 75% of TR) and duration to TR (time after the last dose until recovery of TR) were recorded. RESULTS: Incremental doses of cisatracurium, median (range), were 2 (1-3) in ISO and 4 (2-5) in PPF to achieve ≥95% depression of ST/T0 (p < 0.01). ED50 and ED95 were 20 µg kg-1 and 117 µg kg-1 in ISO and 128 µg kg-1 and 167 µg kg-1 in PPF, respectively. The duration 25%, recovery index and duration to TR, median (range), were longer in ISO [22.6 (10.3-24.3), 5.3 (3.0-7.8) and 36.1 (20.1-49.7) minutes, respectively] than in PPF [10.2 (6.8-16.5), 3.0 (2.0-3.8) and 17.7 (14.2-28.7) minutes, respectively] (p < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Cisatracurium-induced neuromuscular blockade was significantly enhanced and prolonged by isoflurane compared with propofol.

VUV Photoelectron Spectroscopy of Cysteine Aqueous Aerosols: A Microscopic View of Its Nucleophilicity at Varying pH Conditions.

Cysteine (Cys) is unique due to its highly reactive thiol group. It often regulates the biological function of proteins by acting as the redox site. Despite its biological significance, however, the valence electronic structure of Cys under the aqueous environments remains unavailable. Here, we report the VUV photoelectron spectroscopy of Cys aqueous aerosols via a newly built aerosol VUV photoelectron spectroscopy apparatus. The photoelectron spectra of Cys show distinct band shapes at varying pH conditions, reflecting the altered molecular orbital characters when its dominating form changes. The ionization energy of Cys is determined to be 8.98 ± 0.05 eV at low pH. A new feature at a binding energy of 6.97 ± 0.05 eV is observed at high pH, suggesting that the negative charge on the thiolate group becomes the first electron to be removed upon ionization. This work implies that when Cys is involved in redox processes, the charge transfer mechanism may be entirely altered under different pH conditions.

Subunit disassembly pathway of human hemoglobin revealing the site-specific role of its cysteine residues.

Cysteine residues play a unique role in human hemoglobin (Hb) by affecting its cooperative oxygen binding behavior and the stability of its tetrameric structure. However, how these cysteine residues fulfill their biophysical functions from the molecular level is yet unclear. Here we study the subunit disassembly pathway of human hemoglobin using the sulfhydryl reagent, p-hydroxymercuribenzoate (PMB) and investigate the functional roles of cysteine residues in human hemoglobin. We show evidence from the matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry that all three types of cysteine residues, including the surface-exposed ßCys93 and the shielded αCys104 and ßCys112 are reactive to PMB, resolving an issue long under debate. It is demonstrated that all three types of cysteine residues must be blocked by PMB to accomplish the subunit disassembly, and the PMB-cysteine reactions proceed in a stepwise manner with an order of ßCys93, αCys104, and ßCys112. The PMB reactions with the three different cysteine residues demonstrate strong site-specificity. The possible influence of PMB-cysteine reactions to the stability of various intersubunit salt bridges has been discussed based on the crystallographic structure of hemoglobin, providing insights in understanding the hemoglobin subunit disassembly pathway and the site-specific functional role of each cysteine residue in hemoglobin.