SB-258585 reduces food motivation while blocking 5-HT6 receptors in the non-human primate striatum.

The interest in new 5-HT6 agents stems from their ability to modulate cognition processing, food motivation and anxiety-like behaviors. While these findings come primarily from rodent studies, no studies on primates have been published. Furthermore, our understanding of where and how they act in the brain remains limited. Although the striatum is involved in all of these processes and expresses the highest levels of 5-HT6 receptors, few studies have focused on it. We thus hypothesized that 5-HT6 receptor blockade would influence food motivation and modulate behavioral expression in non-human primates through striatal 5-HT6 receptors. This study thus aimed to determine the effects of acute administration of the SB-258585 selective 5-HT6 receptor antagonist on the feeding motivation and behaviors of six male macaques. Additionally, we investigated potential 5-HT6 targets using PET imaging to measure 5-HT6 receptor occupancy throughout the brain and striatal subregions. We used a food-choice task paired with spontaneous behavioral observations, checking 5-HT6 receptor occupancy with the specific PET imaging [18F]2FNQ1P radioligand. We demonstrated, for the first time in non-human primates, that modulation of 5-HT6 transmission, most likely through the striatum (the putamen and caudate nucleus), significantly reduces food motivation while exhibiting variable, weaker effects on behavior. While these results are consistent with the literature showing a decrease in food intake in rodents and proposing that 5-HT6 receptor antagonists can be used in obesity treatment, they question the antagonists' anxiolytic potential.

Location of Trigger Points in a Group of Police Working Dogs: A Preliminary Study.

This study examined the percentage and location of trigger points in police working dogs. Twelve dogs housed at a military police kennel were selected through convenience sampling. Only active dogs with no comorbidities or radiographic changes doing 6 hours of intense physical activity per day were included. After orthopedic and neurological examination, dogs were palpated for the detection of trigger points (TPs), carried out by two independent examiners, with criteria of palpations previously standardized. TPs were recorded using an anatomy reference image according to the corresponding anatomical location. The percentage of TPs was highest in the lumbar portion of the longissimus dorsi muscle (42%), followed by the latissimus dorsi, pectineus, quadriceps femoris, and sartorius (33%) muscles. Most TPs were located on the right side of the body. This study's percentage of TPs in police working dogs was higher in spinal and hind limb muscles, especially on the right side. The major criteria for identifying TPs in dogs were the pain responses to palpation and contractile local response. The findings of this study could be used to refine myofascial pain prevention to reduce early retirement due to musculoskeletal pain and draw attention to this kind of problem that can also affect dogs.

Comparison of intramuscular alfaxalone with medetomidine-ketamine for inducing anaesthesia in Trachemys scripta spp. undergoing sterilization.

OBJECTIVE: To compare the effect of two anaesthetic protocols on heart rate (HR), time to muscle relaxation and tracheal intubation and time to surgical plane of anaesthesia, in Trachemys scripta spp. undergoing oophorectomy. STUDY DESIGN: Prospective randomized clinical study. ANIMALS: A total of 43 healthy female turtles. METHODS: Morphine (1.5 mg kg-1) was injected subcutaneously 2 hours before anaesthesia induction. The turtles were randomly administered either medetomidine (0.2 mg kg-1) and ketamine (10 mg kg-1) (group MK; n = 23) or alfaxalone (20 mg kg-1) (group A; n = 20) intramuscularly followed by bupivacaine (2 mg kg-1) administered subcutaneously along the incision site. Anaesthesia was maintained with isoflurane delivered in oxygen (100%). HR and the anaesthetic depth score (ADS) were recorded every 5 minutes from induction to recovery. A Friedman test followed by Wilcoxon tests with Bonferroni adjustment were used to compare these non-parametric data (HR and ADS) between groups and over time. Time to muscle relaxation of neck and limbs (TMR), tracheal tube insertion (TTTI) and stage of surgical anaesthesia (TADS≤3) were recorded and compared between groups using a Welch's t test after logarithmic transformation. RESULTS: Median values of TMR, TTTI and TADS≤3 were 4, 9.5 and 25 minutes in group A, respectively, and 14, 20 and 35 minutes in group MK (TMR, TTTIp ≤ 0.0001; TADS≤3p = 0.001). Plane of anaesthesia was significantly deeper in group A than in group MK for the first 20 minutes (p < 0.01). HR at 10 and 15 minutes post injection was significantly lower in group MK (28 beats minute-1) than in group A (36 and 34 beats minute-1) (p < 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: After intramuscular injection in Trachemys scripta spp., tracheal intubation, muscle relaxation and a surgical plane of anaesthesia developed faster with alfaxalone than medetomidine-ketamine.

Evaluation of the practical clinical use of the Horse Grimace Scale translated into French.

OBJECTIVE: To assess the reliability of a French version of the Horse Grimace Scale (HGSfv). STUDY DESIGN: Prospective, randomized, clinical study. ANIMALS: The operated (OP) group included 13 horses undergoing elective surgery. The positive (PC) and negative control (NC) groups included seven colicking horses and eight exercising sport horses, respectively. METHODS: Photographs were extracted from videos of the horses' heads. Videos were taken before and immediately after surgery in OP, on arrival of the horse in PC, and at rest in their stalls in NC. Pictures were evaluated by three anaesthetists [Diplomates (DIPs)] and four riders (RIDs) using Horse Grimace Scale translated into French (HGSfv) at two points, 2 weeks apart (E1 and E2). Each evaluator gave each image a score (1-3) for six identified facial action units. The scores given by DIPs and RIDs were compared using a Wilcoxon test. Intra- and inter-evaluator reliability were assessed using Spearman correlation tests (rs) and intra-class coefficients (ICCs), respectively. RESULTS: RIDs and DIPs gave significantly higher scores in the PC group than in the NC group [RIDsE1PC 5.0 (4.2-9.8) versus RIDsE1NC 2.2 (0.0-6.5), p = 0.02; RIDsE2PC 5.2 (3.2-9.5) versus RIDsE2NC 2.0 (0.2-5.8), p < 0.01; DIPsE1PC 4.0 (1.3-6.3) versus DIPsE1NC 2.2 (1.0-4.7), p = 0.04; DIPsE2PC 2.7 (1.0-6.0) versus DIPsE2NC 1.0 (0.0-2.3), p = 0.03]. Scores given by RID or DIPs 2 weeks apart were highly correlated [rs (RIDsE1, RIDsE2) r = 0.86, p < 0.0001] and [rs (DIPsE1, DIPsE2) r = 0.81 p < 0.0001]. The ICC between RIDs and DIPs in E1 and E2 was 0.94 (0.92-0.95) and 0.91 (0.89-0.93), respectively. The specificity and sensitivity of the HGSfv was 94% and 43%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Using the HGSfv, knowledge of horses rather than specialization in veterinary anaesthesia and analgesia appears to differentiate horses with visceral pain from those assumed to be pain free.

A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs.

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.

Effects of dobutamine on cardiovascular function and oxygen delivery in standing horses.

Dobutamine is routinely used to improve cardiovascular function in anaesthetized horses. However, dobutamine in conscious horses is insufficiently investigated. Ten research horses that were already instrumented for a preceding trial were included into the study. Cardiovascular variables were recorded and blood samples taken after instrumentation (Baseline), before starting dobutamine and after 10 min of dobutamine infusion (2 µg kg-1  min-1 ). A significant increase in systemic blood pressure, mean pulmonary artery pressure and right atrial pressure, and a decrease in heart rate were observed with dobutamine compared with baseline measurements. Arterial and mixed venous haemoglobin and oxygen content, as well as mixed venous partial pressure of oxygen increased. No significant changes in cardiac output, stroke volume, systemic vascular resistance, arterial partial pressure of oxygen, or oxygen consumption, delivery and extraction ratio were detected. Concluding, dobutamine increased systemic blood pressure without detectable changes in stroke volume, cardiac output or systemic vascular resistance in conscious horses.

Risk Factors of Anesthesia-Related Mortality and Morbidity in One Equine Hospital: A Retrospective Study on 1,161 Cases Undergoing Elective or Emergency Surgeries.

A retrospective analysis was performed to determine mortality and morbidity rates for elective and emergency cases in an equine university teaching hospital. It investigated the effect of horse-, anesthetic-, timing, and clinician experience-related variables on anesthetic complications. In total, 1,161 horses undergoing general anesthesia between January 2012 and December 2016 were included in the study. Patient information and details of the anesthetic, recovery period and immediate complications were retrieved from an archival database. Statistical analysis of qualitative and quantitative factors affecting anesthetic complications was performed using an univariable and multivariable ordinal logistic regression. Odds ratio of variables primarily affecting mortality and complications were calculated. Statistical significance was set at p < 0.05. General anesthesia-related global mortality rate was 1.4% (95% CI [7.1-10.4]) but was only 0.96% (95% CI [0.44-1.82]) for non-colic cases. The complication rate was 17.5% (n = 204; 95% CI [15.2-20.0]) of which 46.9% [39.4-54.5] were neuromuscular, 22.6% [16.7-29.5] were respiratory, 15.8% [10.8-22.0] were systemic, 13.6% [8.9-19.5] were cardiovascular, 1.1% [0.1-4.0] were other complications. Ninety two percent of complications occurred during recovery. Major risk factors for mortality and complications included high weight, surgeon experience, increasing age, high ASA score, long duration of anesthesia, quality of induction, lateral recumbency, orthopedic surgery, and hypotension. In these models, colic surgery did not influence the rate of any complications.

The ASA Physical Status Classification: What Is the Evidence for Recommending Its Use in Veterinary Anesthesia?-A Systematic Review.

Background: The effectiveness of the American Society of Anesthesiologists (ASA) Physical Status (PS) classification to identify the animals at a greater risk of anesthesia-related death and complications is controversial. In this systematic review, we aimed to analyze studies associating the ASA PS scores with the outcome of anesthesia and to verify whether there was any evidence for recommending the use of the ASA PS in veterinary patients. Methods: Research articles found through a systematic literature search were assessed for eligibility, and data were extracted and analyzed using random-effects analysis. Results: A total of 15 observational prospective and retrospective studies including 258,298 dogs, cats, rabbits, and pigs were included. The analysis found consistency between the studies showing that dogs, cats and rabbits with an ASA-PS ≥III had 3.26 times (95% CI = 3.04-3.49), 4.83 times (95% CI = 3.10-7.53), and 11.31 times (95% CI = 2.70-47.39), respectively, the risk of anesthesia-related death within 24 h (dogs) and 72 h (cats and rabbits) after anesthesia compared with those with an ASA PS

Pharmacokinetics of intramuscular alfaxalone and its echocardiographic, cardiopulmonary and sedative effects in healthy dogs.

The pharmacokinetics and the effects of a single intramuscular (IM) dose of alfaxalone on sedation and cardiopulmonary and echocardiographic variables was studied in dogs. Twelve healthy adult Beagles (3 females, 9 males) were used in this prospective controlled cross-over trial. Echocardiography was performed with and without 4 mg kg-1 alfaxalone IM with a week wash-out interval. Sedation (19-point scale; 0 = no sedation), cardiopulmonary parameters, blood gas analysis and plasma concentration of alfaxalone were assessed every 5 minutes following the injection (T0). The influence of the alfaxalone plasma concentration and time on physiological variables was tested using a linear model whereas echocardiographic measurements were compared between conscious and alfaxalone-administered dogs using paired t-tests. Compared to baseline, alfaxalone administration was followed by an increase in heart rate (HR) from T5 to T30 and a decrease in mean arterial pressure (MAP) at T10, T25 and T30, in stroke volume (SV; 15 ± 5 to 11 ± 3 ml; P<0.0001), and end-diastolic volume (EDV; 24.7 ± 5.7 to 19.4 ± 4.9 ml). Cardiac output (CO) and blood gas analysis did not change significantly throughout. Mean plasma half-life was 29 ± 8 minutes, volume of distribution was 1.94 ± 0.63 L kg-1, and plasma clearance was 47.7 ± 14.1 ml kg-1 minute-1. Moderate to deep sedation was observed from T5 to T35. Ten dogs showed paddling, trembling, nystagmus and strong reaction to sound during the procedure. Although there were no significant changes in CO and oxygenation, the impact of HR, MAP, SV, EDV alterations requires further investigations in dogs with cardiac disease.

The Modification and Performance of a Large Animal Anesthesia Machine (Tafonius®) in Order to Deliver Xenon to a Horse.

INTRODUCTION: Xenon, due to its interesting anesthetic properties, could improve the quality of anesthesia protocols in horses despite its high price. This study aimed to modify and test an anesthesia machine capable of delivering xenon to a horse. MATERIALS AND METHODS: An equine anesthesia machine (Tafonius, Vetronic Services Ltd., UK) was modified by including a T-connector in the valve block to introduce xenon, so that the xenon was pushed into the machine cylinder by the expired gases. A xenon analyzer was connected to the expiratory limb of the patient circuit. The operation of the machine was modeled and experimentally tested for denitrogenation, wash-in, and maintenance phases. The system was considered to consist of two compartments, one being the horse's lungs, the other being the machine cylinder and circuit. A 15-year-old, 514-kg, healthy gelding horse was anesthetized for 70 min using acepromazine, romifidine, morphine, diazepam, and ketamine. Anesthesia was maintained with xenon and oxygen, co-administered with lidocaine. Ventilation was controlled. Cardiorespiratory variables, expired fraction of xenon (FeXe), blood gases were measured and xenon was detected in plasma. Recovery was unassisted and recorded. RESULTS: FeXe remained around 65%, using a xenon total volume of 250 L. Five additional boli of ketamine were required to maintain anesthesia. PaO2 was 45 ± 1 mmHg. The recovery was calm. Xenon was detected in blood during the entire administration time. CONCLUSION: This pilot study describes how to deliver xenon to a horse. Although many technical problems were encountered, their correction could guide future endeavors to study the use of xenon in horses.

Sedative and cardiovascular effects of intranasal or intramuscular dexmedetomidine in healthy dogs.

OBJECTIVE: To compare the clinical effects and sedation scores following either intranasal (IN) or intramuscular (IM) administration of dexmedetomidine in dogs. STUDY DESIGN: Prospective, blinded, randomized, clinical study. ANIMALS: A total of 20 client-owned dogs scheduled for noninvasive diagnostic procedures. METHODS: Dogs were allocated to be administered dexmedetomidine 0.02 mg kg-1 IN (IN group) or IM (IM group). Sedation was scored before and at 5 minute intervals (for 45 minutes) after drug administration using a composite simple descriptive sedation scale giving a score of 0 (not sedated) to 13 (well sedated). Respiratory frequency (fR), heart rate, haemoglobin oxygen saturation (SpO2) and noninvasive arterial blood pressure were recorded every 5 minutes for 45 minutes. Normally distributed data were analyzed using two-way ANOVA and post hoc Sidak's multiple comparison test. Non-normally distributed data were compared using the Scheier Ray Hare test and post hoc Mann-Whitney U test. Statistical significance was set at p<0.05. RESULTS: Weight, age and sex were not different between groups. Dexmedetomidine onset of action after IN administration was not shorter compared to IM administration (6.3±3.3 versus 9.4±4.6 minutes, p=0.120). Sedation score in the IN group was higher [10 (0-11)] compared to the IM group [6 (0-8)] (p<0.001). At time of peak sedation, heart rate decreased 56% from baseline values in the IM group, and 18% in the IN group. No significant differences in SpO2 and fR were found between the two groups at any time point. No undesirable effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal dexmedetomidine 0.02 mg kg-1 produced effective sedation with less bradycardia and more profound sedation compared to IM administration in healthy dogs and may be considered as an alternative route for dexmedetomidine administration in dogs.

Comparison of the effects of an intravenous lidocaine infusion combined with 1% isoflurane versus 2% isoflurane alone on selected cardiovascular variables and recovery characteristics during equine general anaesthesia.

OBJECTIVES: To compare the effects of a lidocaine constant rate infusion (CRI) combined with 1% isoflurane versus those of 2% isoflurane alone on cardiovascular variables in anaesthetized horses, and to estimate the sample size required to detect a difference in recovery quality. STUDY DESIGN: Prospective, randomized, blinded, crossover study. ANIMALS: Twelve healthy experimental horses. METHODS: Horses were anaesthetized twice using an intravenous (IV) administration of acepromazine, romifidine, diazepam and ketamine. Horses were placed in dorsal recumbency and ventilated mechanically. During the first 10 minutes (P1), anaesthesia was maintained with a 2% inspired isoflurane fraction (FIIso). During the following 20 minutes (P2), horses received IV lidocaine (1.5 mg kg-1) (group IL) or saline (group I). During the last 60 minutes (P3), group IL received a lidocaine CRI (50 µg kg-1 minute-1 IV) and FIIso 1%, whereas group I received a saline CRI and FIIso 2%. Three weeks later, the horses received the alternative treatment. Painful stimuli were induced by introducing an 18 gauge needle intramuscularly. Ketamine and dobutamine requirements and physiological variables were recorded. Recoveries were assessed by two anaesthetists unaware of the treatment. Lidocaine plasma concentrations were measured during recovery. Data were analysed with anova. RESULTS: During P3, group IL had a lower heart rate (p = 0.002), higher mean arterial pressure (p < 0.001) and lower dobutamine requirement (p < 0.001) than group I. One horse had lidocaine plasma concentrations above toxic levels. Recoveries did not differ significantly between groups. Sample sizes of 208 horses in each group would be necessary to detect a statistically significant difference (85% statistical power) in recovery quality. CONCLUSIONS AND CLINICAL RELEVANCE: A lidocaine CRI combined with FIIso 1% rather than FIIso 2% alone may improve cardiovascular variables in healthy anaesthetized horses.

Alfaxalone for total intravenous anaesthesia in bitches undergoing elective caesarean section and its effects on puppies: a randomized clinical trial.

OBJECTIVE: To evaluate the effects and reliability of alfaxalone constant rate infusion (CRI) in comparison to isoflurane to maintain anaesthesia in bitches undergoing elective caesarean section. STUDY DESIGN: Prospective, randomized, 'blinded' clinical trial. ANIMALS: Twenty-two client-owned bitches and 94 puppies. METHODS: Bitches were randomly assigned to receive an alfaxalone CRI [0.2 mg kg(-1)  minute(-1) intravenously (IV), and once the last puppy was delivered, the dose was halved; n = 11] or 2% (vaporizer dial setting) isoflurane (n = 11) for maintenance of anaesthesia. All dogs were induced with alfaxalone (3 mg kg(-1) ) IV. Additional alfaxalone (0.3 mg kg(-1) IV) was administered if the depth of anaesthesia was inadequate and the total dose was calculated. Bitches were mechanically ventilated. Analgesia was administered after the delivery of puppies. Physiological variables were recorded every 5 minutes. The bitches' recovery times were also recorded. Quality of induction and recovery were evaluated. Puppies' vigour was evaluated with a modified Apgar score at 5 and 60 minutes after birth. Puppies' survival rates at 24 and 48 hours and at 15 days were recorded. Data were analysed using an anova, Student's t-test or Wilcoxon rank-sum test. RESULTS: The rescue dose of alfaxalone was higher (p = 0.01); bitches' recoveries were longer (p < 0.001) and puppies' Apgar scores were significantly lower at 5 and 60 minutes (p < 0.001 and p = 0.003, respectively) with alfaxalone than with isoflurane. However, no significant differences were found for puppies' survival between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone CRI seems to be a possible protocol for puppies and bitches undergoing elective caesarean sections. However, bitches recovered more slowly and puppy Apgar scores were lower in comparison to isoflurane.

Evaluation of the non-calibrated pulse contour cardiac output monitor FloTrac/Vigileo against thermodilution in standing horses.

OBJECTIVE: To evaluate the non-calibrated, minimally invasive cardiac output (CO) monitor FloTrac/Vigileo (FloTrac) against thermodilution (TD) CO in standing horses. STUDY DESIGN: Prospective, experimental trial. ANIMALS: Nine adult horses weighing a median (range) of 535 (470-602) kg. METHODS: Catheters were placed in the right atrium, pulmonary artery and carotid artery under local anaesthesia. CO was measured 147 times by TD and FloTrac and indexed to body weight. Changes in CO were achieved with romifidine or xylazine and dobutamine constant rate infusions. Bland-Altman analysis, concordance and polar plot analysis were used to assess agreement and ability to track changes in CO. RESULTS: Mean ± standard deviation COTD of 48 ± 16 mL kg(-1) minute(-1) (range: 19-93 mL kg(-1) minute(-1) ) and mean COF loTrac of 9 ± 3 mL kg(-1) minute(-1) (range: 5-21 mL kg(-1) minute(-1) ) were measured. Low agreement with a large mean bias of 39 mL kg(-1) minute(-1) and wide limits of agreement of 8-70 mL kg(-1) minute(-1) were found. The percentage error of 108% and precision of TD of ± 18% resulted in an estimated precision of FloTrac of ± 106%. Comparison of changes in COF loTrac with changes in COTD gave a concordance rate of 52% in the four-quadrant plot, and a mean polar angle of -11° with radial limits of agreement of ± 61 ° in the polar plot. Mean arterial pressure (MAP) and COF loTrac were positively correlated (r = 0.5, p < 0.0001). No correlation of MAP with COTD was observed. CONCLUSIONS AND CLINICAL RELEVANCE: The FloTrac system, originally designed for use in humans, neither measured absolute CO in standing horses accurately nor tracked relative changes in CO measured by TD correctly. The false dependence of COF loTrac on arterial blood pressure further discourages the use of this technique in horses.

Effect of Pre- and Postoperative Phenylbutazone and Morphine Administration on the Breathing Response to Skin Incision, Recovery Quality, Behavior, and Cardiorespiratory Variables in Horses Undergoing Fetlock Arthroscopy: A Pilot Study.

This prospective blinded randomized study aimed to determine whether the timing of morphine and phenylbutazone administration affects the breathing response to skin incision, recovery quality, behavior, and cardiorespiratory variables in horses undergoing fetlock arthroscopy. Ten Standardbred horses were premedicated with acepromazine (0.04 mg kg(-1) IM) and romifidine (0.04 mg kg(-1) IV). Anesthesia was induced with diazepam (0.05 mg kg(-1)) and ketamine (2.2 mg kg(-1)) IV at T0. Horses in group PRE (n = 5) received morphine (0.1 mg kg(-1)) and phenylbutazone (2.2 mg kg(-1)) IV after induction and an equivalent amount of saline after surgery. Horses in group POST (n = 5) received the inversed treatment. Anesthesia was maintained with isoflurane 2% in 100% oxygen. Hypotension (mean arterial pressure <60 mmHg) was treated with dobutamine. All horses breathed spontaneously. Dobutamine requirements, respiratory rate (f R), heart rate (HR), mean arterial blood pressure, end-tidal CO2, inspired (i) and expired (e) tidal and minute volume (V T and [Formula: see text]), inspiratory time (IT), and the inspiratory gas flow (V Ti/IT) were measured every 5 min. Data were averaged during four 15 min periods before (P1 and P2) and after the incision (P3 and P4). Serial blood-gas analyses were also performed. Recoveries were unassisted, video recorded, and scored by three anesthetists blinded to the treatment. The postoperative behavior of the horses (25 demeanors), HR, and f R were recorded at three time points before induction (T0-24 h, T0-12 h, and T0-2 h) and six time points after recovery (TR) (TR + 2, 4, 6, 12, 24, 48 h). Data were compared between groups using a Wilcoxon test and within groups using a Friedman test or a Kruskal-Wallis signed-rank test when applicable. Tidal volumes (V Te and V Ti) were higher in PRE than in POST during all the considered periods but the difference between groups was only significant during P2 (V Te in mL kg(-1) in PRE: 13 [9, 15], in POST: 9 [8, 9], p = 0.01). None of the other variables were significantly different between and within groups. Under our experimental conditions, skin incision did not affect respiratory variables. Administration of pre- versus postoperative phenylbutazone and morphine did not influence recovery quality, HR, f R, or animal behavior.

Synergistic protective effect of cyclosporin A and rotenone against hypoxia-reoxygenation in cardiomyocytes.

Reperfusion of the heart after an ischemic event leads to the opening of a nonspecific pore in the inner mitochondrial membrane, the mitochondrial permeability transition pore (mPTP). Inhibition of mPTP opening is an effective strategy to prevent cardiomyocyte death. The matrix protein cyclophilin-D (CypD) is the best-known regulator of mPTP opening. In this study we confirmed that preconditioning and postconditioning with CypD inhibitor cyclosporin-A (CsA) reduced cell death after hypoxia-reoxygenation (H/R) in wild-type (WT) cardiomyocytes and HL-1 mouse cardiac cell line as measured by nuclear staining with propidium iodide. The complex I inhibitor rotenone (Rot), alone, had no effect on HL-1 and WT cardiomyocyte death after H/R, but enhanced the native protection of CypD-knocked-out (CypD KO) cardiomyocytes. Reduction of cell death was associated with a delay of mPTP opening challenged by H/R and observed by the calcein loading CoCl(2)-quenching technique. Simultaneous inhibition of complex I and CypD increased in a synergistic manner the calcium retention capacity in permeabilized cardiomyocytes and cardiac mitochondria. These results demonstrated that protection by complex I inhibition was CypD dependent.

Effects on cardiopulmonary function and oxygen delivery of doses of romifidine and xylazine followed by constant rate infusions in standing horses.

The objective of this study was to compare the cardiopulmonary effects of a xylazine or romifidine loading-dose, followed by a constant rate infusion (CRI) of the same α(2)-agonist. Nine research horses were treated in a randomized, blinded, crossover design with xylazine or romifidine. After instrumentation, a loading dose of intravenous xylazine (1mg/kg) or romifidine (80µg/kg) was administered, immediately followed by a CRI of xylazine (0.69mg/kg/h) or romifidine (30µg/kg/h) for a duration of 2h. Cardiopulmonary variables were recorded before bolus administration, during CRI, and for 1h after discontinuing drug administration. A significant decrease in haemoglobin concentration (tHb), arterial oxygen content (CaO(2)), oxygen delivery (D˙O(2)), mixed venous partial pressure of oxygen, heart rate, and cardiac output (Q˙t) followed the loading dose with both treatments. Carotid arterial blood pressure (ABP), systemic vascular resistance, and right atrial pressure (RAP) increased significantly. The increased ABP was followed by a significant decrease compared to baseline. Mean pulmonary arterial pressure increased significantly with romifidine only. No significant changes in stroke volume, arterial partial pressure of oxygen, and oxygen consumption were observed. Changes in Q˙t and RAP were more pronounced with romifidine. During CRI, tHb, and CaO(2) were significantly higher with romifidine, whereas D˙O(2) did not differ between treatments. Overall, cardiopulmonary effects were more pronounced and lasted longer with romifidine compared to xylazine. However, during CRI, there was no difference in D˙O(2) between drugs. With both α(2)-agonists, cardiovascular effects were most pronounced after loading dose administration and tended to stabilize during CRI.