Evaluation of cardiovascular effects of intramuscular medetomidine and a medetomidine-vatinoxan combination in Beagle dogs: A randomized blinded crossover laboratory study.

OBJECTIVE: To compare the cardiovascular effects of a combination of medetomidine and vatinoxan (MVX) versus medetomidine (MED) alone administered intramuscularly (IM) and to determine whether heart rate (HR) can be used as a surrogate for cardiac output (CO) after the use of medetomidine with or without vatinoxan. STUDY DESIGN: A randomized, blinded, experimental, crossover study. ANIMALS: A group of eight healthy Beagle dogs aged 4.6 (2.3-9.4) years and weighing 12.9 (9-14.7) kg, median (range). METHODS: Each dog was injected with 1 mg m-2 medetomidine with or without 20 mg m-2 vatinoxan IM with a washout period of 7 days. Cardiovascular data and arterial and mixed venous blood gas samples were collected at baseline, 5, 10, 15, 20, 35, 45, 60, 90 and 120 minutes after treatment administration. CO was measured at all time points via thermodilution. Differences between treatments, period and sequence were evaluated with repeated measures analysis of covariance and the relationship between HR and CO was assessed with a repeated measures analysis of variance; p values < 0.05 were deemed significant. RESULTS: The CO was 47-96% lower after MED than after MVX (p < 0.0001). Increases in systemic, pulmonary arterial and right atrial pressures and oxygen extraction ratio were significantly higher after MED than after MVX (all p < 0.0001). HR was significantly lower after MED and the linear relationship to CO was significant (p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: Overall, MED affected the cardiovascular system more negatively than MVX, and the difference in cardiovascular function between the treatments can be considered clinically relevant. HR was linearly related to CO, and decreases in HR reflected cardiac performance for dogs sedated with medetomidine with or without vatinoxan.

The impact of vatinoxan on microcirculation after intramuscular co-administration with medetomidine in Beagle dogs: a blinded crossover study.

OBJECTIVE: To measure the effects on microcirculation of medetomidine alone (MED) or combined with vatinoxan (MVX). STUDY DESIGN: Randomized, crossover, blinded, experimental study. ANIMALS: A group of eight healthy purpose-bred Beagle dogs. METHODS: Each dog was given 1 mg m-2 MED intramuscularly (IM) or combined with 20 mg m-2 vatinoxan IM (MVX) with a washout period of 7 days. A sidestream dark field (SDF) camera was placed on the buccal mucosa to assess the oral mucosal microcirculation for perfused DeBacker density, proportion of perfused vessels (PPV) (both for all vessels and vessels with a diameter < 20 µm), microvascular flow index (MFI) and heterogeneity index (HI). Videos were recorded at baseline (-5) and 10, 20, 30, 40, 60, 90 and 120 minutes after treatment administration. Linear mixed-effects models were used to assess if microvascular variables were significantly associated with treatment, baseline, and sequence. Results are presented as estimated effect (95% confidence interval), and a p value < 0.05 was considered significant. RESULTS: The interquartile range for baseline measurements was 91.49%-98.42% for PPV, 2.75-3 for MFI and 0-0.36 for HI. Significant effects of treatment and baseline were found. The estimated effect of MED against MVX was -1.98% (-3.53% to -0.42%) for PPV, -0.33 (-0.43 to -0.22) for MFI and 0.14 (0.05 to 0.22) for HI. There were no significant changes seen for perfused DeBacker density, perfused DeBacker density < 20 µm and PPV < 20 µm between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that MVX had significantly fewer effects on buccal mucosal microcirculation than MED. The SDF camera is a useful research tool to assess the microcirculatory status of heavily sedated dogs.

Ketamine administration in idiopathic epileptic and healthy control dogs: Can we detect differences in brain metabolite response with spectroscopy?

Introduction: In recent years ketamine has increasingly become the focus of multimodal emergency management for epileptic seizures. However, little is known about the effect of ketamine on brain metabolites in epileptic patients. Magnetic resonance spectroscopy (MRS) is a non-invasive technique to estimate brain metabolites in vivo. Our aim was to measure the effect of ketamine on thalamic metabolites in idiopathic epileptic (IE) dogs using 3 Tesla MRS. We hypothesized that ketamine would increase the glutamine-glutamate (GLX)/creatine ratio in epileptic dogs with and without antiseizure drug treatment, but not in control dogs. Furthermore, we hypothesized that no different responses after ketamine administration in other measured brain metabolite ratios between the different groups would be detected. Methods: In this controlled prospective experimental trial IE dogs with or without antiseizure drug treatment and healthy client-owned relatives of the breeds Border Collie and Greater Swiss Mountain Dog, were included. After sedation with butorphanol, induction with propofol and maintenance with sevoflurane in oxygen and air, a single voxel MRS at the level of the thalamus was performed before and 2 min after intravenous administration of 1 mg/kg ketamine. An automated data processing spectral fitting linear combination model algorithm was used to estimate all commonly measured metabolite ratios. A mixed ANOVA with the independent variables ketamine administration and group allocation was performed for all measured metabolites. A p < 0.05 was considered statistically significant. Results: Twelve healthy control dogs, 10 untreated IE and 12 treated IE dogs were included. No significant effects for GLX/creatine were found. However, increased glucose/creatine ratios were found (p < 0.001) with no effect of group allocation. Furthermore, increases in the GABA/creatine ratio were found in IEU dogs. Discussion: MRS was able to detect changes in metabolite/creatine ratios after intravenous administration of 1 mg/kg ketamine in dogs and no evidence was found that excitatory effects are induced in the thalamus. Although it is beyond the scope of this study to investigate the antiseizure potential of ketamine in dogs, results of this research suggest that the effect of ketamine on the brain metabolites could be dependent on the concentrations of brain metabolites before administration.

Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model.

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model.Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes.Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups.Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

Corrigendum: Development of a Routinely Applicable Imaging Protocol for Fast and Precise Middle Cerebral Artery Occlusion Assessment and Perfusion Deficit Measure in an Ovine Stroke Model: A Case Study.

[This corrects the article DOI: 10.3389/fneur.2019.01113.].

Development of a Routinely Applicable Imaging Protocol for Fast and Precise Middle Cerebral Artery Occlusion Assessment and Perfusion Deficit Measure in an Ovine Stroke Model: A Case Study.

Temporary middle cerebral artery occlusion (MCAO) in sheep allows modeling of acute large vessel occlusion stroke and subsequent vessel recanalization. However, rapid and precise imaging-based assessment of vessel occlusion and the resulting perfusion deficit during MCAO still represents an experimental challenge. Here, we tested feasibility and suitability of a strategy for MCAO verification and perfusion deficit assessment. We also compared the extent of the initial perfusion deficit and subsequent lesion size for different MCAO durations. The rete mirabile prevents reliable vascular imaging investigation of middle cerebral artery filling status. Hence, computed tomography perfusion imaging was chosen for indirect confirmation of MCAO. Follow-up infarct size evaluation by diffusion-weighted magnetic resonance imaging revealed fluctuating results, with no apparent relationship of lesion size with MCAO at occlusion times below 4 h, potentially related to the variable collateralization of the MCA territory. This underlines the need for intra-ischemic perfusion assessment and future studies focusing on the correlation between perfusion deficit, MCAO duration, and final infarct volume. Temporary MCAO and intra-ischemic perfusion imaging nevertheless has the potential to be applied for the simulation of novel recanalization therapies, particularly those that aim for a fast reperfusion effect in combination with mechanical thrombectomy in a clinically realistic scenario.