Combined effects of dexmedetomidine and vatinoxan infusions on minimum alveolar concentration and cardiopulmonary function in sevoflurane-anesthetized dogs

Objective To evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs. Study design Prospective experimental study. Methods A total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 mu g kg(-1) hour(-1)) and after two IV doses of vatinoxan in sequence (90 and 180 mu g kg(-1) hour(-1)). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p 180 mu g kg(-1) hour(-1) might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost.Peer reviewe

Concentrations of medetomidine enantiomers and vatinoxan, an α2-adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs

Objective To quantify the peripheral selectivity of vatinoxan (L-659,066, MK-467) in dogs by comparing the concentrations of vatinoxan, dexmedetomidine and levo-medetomidine in plasma and central nervous system (CNS) tissue after intravenous (IV) coadministration of vatinoxan and medetomidine. Study design Experimental, observational study. Animals A group of six healthy, purpose-bred Beagle dogs (four females and two males) aged 6.5 +/- 0.1 years (mean +/- standard deviation). Methods All dogs were administered a combination of medetomidine (40 mu g kg(-1)) and vatinoxan (800 mu g kg(-1)) as IV bolus. After 20 minutes, the dogs were euthanized with an IV overdose of pentobarbital (140 mg kg(-1)) and both venous plasma and CNS tissues (brain, cervical and lumbar spinal cord) were harvested. Concentrations of dexmedetomidine, levomedetomidine and vatinoxan in all samples were quantified by liquid chromatography-tandem mass spectrometry and data were analyzed with nonparametric tests with post hoc corrections where appropriate. Results All dogs became deeply sedated after the treatment. The CNS-to-plasma ratio of vatinoxan concentration was approximately 1:50, whereas the concentrations of dexmedetomidine and levomedetomidine in the CNS were three- to seven-fold of those in plasma. Conclusions and clinical relevance With the doses studied, these results confirm the peripheral selectivity of vatinoxan in dogs, when coadministered IV with medetomidine. Thus, it is likely that vatinoxan preferentially antagonizes alpha(2)-adrenoceptors outside the CNS.Peer reviewe

Dogs evaluate threatening facial expressions by their biological validity - evidence from gazing patterns

Appropriate response to companions' emotional signals is important for all social creatures. The emotional expressions of humans and non-human animals have analogies in their form and function, suggesting shared evolutionary roots, but very little is known about how animals other than primates view and process facial expressions. In primates, threat-related facial expressions evoke exceptional viewing patterns compared with neutral or positive stimuli. Here, we explore if domestic dogs (Canis familiaris) have such an attentional bias toward threatening social stimuli and whether observed emotional expressions affect dogs' gaze fixation distribution among the facial features (eyes, midface and mouth). We recorded the voluntary eye gaze of 31 domestic dogs during viewing of facial photographs of humans and dogs with three emotional expressions (threatening, pleasant and neutral). We found that dogs' gaze fixations spread systematically among facial features. The distribution of fixations was altered by the seen expression, but eyes were the most probable targets of the first fixations and gathered longer looking durations than mouth regardless of the viewed expression. The examination of the inner facial features as a whole revealed more pronounced scanning differences among expressions. This suggests that dogs do not base their perception of facial expressions on the viewing of single structures, but the interpretation of the composition formed by eyes, midface and mouth. Dogs evaluated social threat rapidly and this evaluation led to attentional bias, which was dependent on the depicted species: threatening conspecifics' faces evoked heightened attention but threatening human faces instead an avoidance response. We propose that threatening signals carrying differential biological validity are processed via distinctive neurocognitive pathways. Both of these mechanisms may have an adaptive significance for domestic dogs. The findings provide a novel perspective on understanding the processing of emotional expressions and sensitivity to social threat in non-primates.Peer reviewe

Reactivity of dogs' brain oscillations to visual stimuli measured with non-invasive electroencephalography

Studying cognition of domestic dogs has gone through a renaissance within the last decades. However, although the behavioral studies of dogs are beginning to be common in the field of animal cognition, the neural events underlying cognition remain unknown. Here, we employed a non-invasive electroencephalography, with adhesive electrodes attached to the top of the skin, to measure brain activity of from 8 domestic dogs (Canis familiaris) while they stayed still to observe photos of dog and human faces. Spontaneous oscillatory activity of the dogs, peaking in the sensors over the parieto-occipital cortex, was suppressed statistically significantly during visual task compared with resting activity at the frequency of 15–30 Hz. Moreover, a stimulus-induced low-frequency (~2–6 Hz) suppression locked to the stimulus onset was evident at the frontal sensors, possibly reflecting a motor rhythm guiding the exploratory eye movements. The results suggest task-related reactivity of the macroscopic oscillatory activity in the dog brain. To our knowledge, the study is the first to reveal non-invasively measured reactivity of brain electrophysiological oscillations in healthy dogs, and it has been based purely on positive operant conditional training, without the need for movement restriction or medication.Peer reviewe

Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route.

Objective: To study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously administered detomidine. Study design: Randomised, prospective clinical study. Animals: Twenty dairy calves aged 12.4 ± 4.4 days (mean ± SD), weight 50.5 ± 9.0 kg. Methods: Detomidine at 80 μg kg-1 was administered to ten calves sublingually (GEL) and at 30 μg kg-1 to ten control calves intravenously (IV). Meloxicam (0.5 mg kg-1) and  local anaesthetic (lidocaine 3 mg kg-1) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over  240 minutes. Blood was collected during the same period for drug concentration  analysis. Pharmacokinetic variables were calculated from the plasma detomidine  concentration-time data using non-compartmental methods.  Results: The maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng  mL-1 (mean ± SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation  scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding. Conclusions and clinical relevance: Oromucosally administered detomidine is an  effective sedative agent for calves prior to disbudding.Peer reviewe

Effects of vatinoxan in dogs premedicated with medetomidine and butorphanol followed by sevoflurane anaesthesia : a randomized clinical study

Publisher Copyright: © 2022 The Author(s)Objective: To investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration. Study design: A randomized, controlled, blinded, clinical trial. Animals: A total of 28 client-owned dogs. Methods: Dogs were premedicated with medetomidine (0.125 mg m−2) and butorphanol (0.2 mg kg−1) (group MB; n = 14), or medetomidine (0.25 mg m−2), butorphanol (0.2 mg kg−1) and vatinoxan (5 mg m−2) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg−1) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg−1) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (fR), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (FE′Sevo) and carbon dioxide (PE′CO2) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations. Results: At the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute−1 (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in fR, PE′CO2, FE′Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups. Conclusions and clinical relevance: In group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups.Peer reviewe

Visual event-related potentials of dogs: a non-invasive electroencephalography study

Previously, social and cognitive abilities of dogs have been studied within behavioral experiments, but the neural processing underlying the cognitive events remains to be clarified. Here, we employed completely non-invasive scalp-electroencephalography in studying the neural correlates of the visual cognition of dogs. We measured visual event-related potentials (ERPs) of eight dogs while they observed images of dog and human faces presented on a computer screen. The dogs were trained to lie still with positive operant conditioning, and they were neither mechanically restrained nor sedated during the measurements. The ERPs corresponding to early visual processing of dogs were detectable at 75–100 ms from the stimulus onset in individual dogs, and the group-level data of the 8 dogs differed significantly from zero bilaterally at around 75 ms at the most posterior sensors. Additionally, we detected differences between the responses to human and dog faces in the posterior sensors at 75–100 ms and in the anterior sensors at 350–400 ms. To our knowledge, this is the first illustration of completely non-invasively mea- sured visual brain responses both in individual dogs and within a group-level study, using ecologically valid visual stimuli. The results of the present study validate the fea- sibility of non-invasive ERP measurements in studies with dogs, and the study is expected to pave the way for further neurocognitive studies in dogs.Previously, social and cognitive abilities of dogs have been studied within behavioral experiments, but the neural processing underlying the cognitive events remains to be clarified. Here, we employed completely non-invasive scalp-electroencephalography in studying the neural correlates of the visual cognition of dogs. We measured visual event-related potentials (ERPs) of eight dogs while they observed images of dog and human faces presented on a computer screen. The dogs were trained to lie still with positive operant conditioning, and they were neither mechanically restrained nor sedated during the measurements. The ERPs corresponding to early visual processing of dogs were detectable at 75–100 ms from the stimulus onset in individual dogs, and the group-level data of the 8 dogs differed significantly from zero bilaterally at around 75 ms at the most posterior sensors. Additionally, we detected differences between the responses to human and dog faces in the posterior sensors at 75–100 ms and in the anterior sensors at 350–400 ms. To our knowledge, this is the first illustration of completely non-invasively mea- sured visual brain responses both in individual dogs and within a group-level study, using ecologically valid visual stimuli. The results of the present study validate the fea- sibility of non-invasive ERP measurements in studies with dogs, and the study is expected to pave the way for further neurocognitive studies in dogs.Peer reviewe

New national and regional biological records for Finland 11. Contributions to Bryophyta and Marchantiophyta 10

Ten species of mosses (Bryophyta: Entosthodon obtusus, Entosthodon ulvinenii, Eurhynchiastrum diversifolium, Hedwigia emodica, Hedwigia mollis, Hygrohypnum styriacum, Plagiothecium rossicum, Polytrichum perigoniale, Tortella alpicola and Ulota intermedia) are presented as new for Finland. Cephalozia lacinulata, previously considered to be regionally extinct from Finland, is reported to being found again. New records in biogeographical provinces for 67 species of mosses and 34 species of liverworts are listed. Finally, 6 occurrences in provinces are removed due to misidentifications or missing specimens

Nasal Oxytocin Treatment Biases Dogs' Visual Attention and Emotional Response toward Positive Human Facial Expressions

The neuropeptide oxytocin plays a critical role in social behavior and emotion regulation in mammals. The aim of this study was to explore how nasal oxytocin administration affects gazing behavior during emotional perception in domestic dogs. Looking patterns of dogs, as a measure of voluntary attention, were recorded during the viewing of human facial expression photographs. The pupil diameters of dogs were also measured as a physiological index of emotional arousal. In a placebo-controlled within-subjects experimental design, 43 dogs, after having received either oxytocin or placebo (saline) nasal spray treatment, were presented with pictures of unfamiliar male human faces displaying either a happy or an angry expression. We found that, depending on the facial expression, the dogs' gaze patterns were affected selectively by oxytocin treatment. After receiving oxytocin, dogs fixated less often on the eye regions of angry faces and revisited (glanced back at) more often the eye regions of smiling (happy) faces than after the placebo treatment. Furthermore, following the oxytocin treatment dogs fixated and revisited the eyes of happy faces significantly more often than the eyes of angry faces. The analysis of dogs' pupil diameters during viewing of human facial expressions indicated that oxytocin may also have a modulatory effect on dogs' emotional arousal. While subjects' pupil sizes were significantly larger when viewing angry faces than happy faces in the control (placebo treatment) condition, oxytocin treatment not only eliminated this effect but caused an opposite pupil response. Overall, these findings suggest that nasal oxytocin administration selectively changes the allocation of attention and emotional arousal in domestic dogs. Oxytocin has the potential to decrease vigilance toward threatening social stimuli and increase the salience of positive social stimuli thus making eye gaze of friendly human faces more salient for dogs. Our study provides further support for the role of the oxytocinergic system in the social perception abilities of domestic dogs. We propose that oxytocin modulates fundamental emotional processing in dogs through a mechanism that may facilitate communication between humans and dogs.Peer reviewe

Investigation of the effects of vatinoxan on somatic and visceral antinociceptive efficacy of medetomidine in dogs

OBJECTIVE To determine whether concurrent vatinoxan administration affects the antinociceptive efficacy of medetomidine in dogs at doses that provide circulating dexmedetomidine concentrations similar to those produced by medetomidine alone. ANIMALS 8 healthy Beagles. PROCEDURES Dogs received 3 IV treatments in a randomized crossover-design trial with a 2-week washout period between experiments (medetomidine [20 mu g/kg], medetomidine [20 mu g/kg] and vatinoxan [400 mu g/kg], and medetomidine [40 mu g/kg] and vatinoxan [800 mu g/kg]; M20, M20V400, and M40V800, respectively). Sedation, visceral and somatic nociception, and plasma drug concentrations were assessed. Somatic and visceral nociception measurements and sedation scores were compared among treatments and over time. Sedation, visceral antinociception, and somatic antinociception effects of M20V400 and M40V800 were analyzed for noninferiority to effects of M20, and plasma drug concentration data were assessed for equivalence between treatments. RESULTS Plasma dexmedetomidine concentrations after administration of M20 and M40V800 were equivalent. Sedation scores, visceral nociception measurements, and somatic nociception measurements did not differ significantly among treatments within time points. Overall sedative effects of M20V400 and M40V800 and visceral antinociceptive effects of M40V800 were non inferior to those produced by M20. Somatic antinociception effects of M20V400 at 10 minutes and M40V800 at 10 and 55 minutes after injection were noninferior to those produced by M20. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested coadministration with vatinoxan did not substantially diminish visceral antinociceptive effects of medetomidine when plasma dexmedetomidine concentrations were equivalent to those produced by medetomidine alone. For somatic antinociception, noninferiority of treatments was detected at some time points.Peer reviewe