A randomized clinical trial comparing the efficacy of lidocaine administered intravenously, intranasally or as infraorbital nerve block in dogs undergoing rostral rhinosocopy.

OBJECTIVE: To compare the efficacy of lidocaine administered intravenously, intranasally or as an infraorbital nerve block in dogs undergoing rostral rhinoscopy. STUDY DESIGN: Randomized clinical trial. ANIMALS: A total of 43 client-owned dogs. METHODS: After premedication with medetomidine 0.01 mg kg-1 and methadone 0.2 mg kg-1 intramuscularly, anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Dogs were randomly allocated to receive 2 mg kg-1 of 2% lidocaine as a bilateral infraorbital nerve block (INB) via the caudal intraoral approach, via bilateral topical intranasal administration (TIA) or as an intravenous bolus (IVB). At 5 minutes following lidocaine administration, responses to rhinoscopy (RR) and biopsies (RB) were evaluated using a simple scoring system (0: no reaction; 1: reaction). Response to the rhinoscopy in the recovery period (RE) was recorded. Recovery quality was scored using a simple descriptive score. Heart rate, respiratory rate and noninvasive arterial blood pressure were recorded. Intravenous (IV) fentanyl 0.001 mg kg-1 was administered if an increase > 20% in any variable occurred. Gross movement was attenuated using propofol 0.5 mg kg-1 IV. Scores were analysed using the Chi-square test with Monte Carlo method. Cardiorespiratory changes among and overtime between groups were compared using one-way anova and one-way anova for repeated measures, respectively, or the correspondent non-parametric tests; p < 0.05. RESULT: Of the 43 dogs, 42 completed the study. No statistically significant differences were detected in either physical reactions or changes in cardiorespiratory variables for RR, RB, RE or recovery quality, although RB tended to be higher in group TIA (7/10 versus 1/10 INB and 3/13 IVB).Various cardiorespiratory variables changed overtime within groups. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, all three investigated techniques attenuated responses during rostral rhinoscopy in dogs, although INB and IVB were more efficacious when biopsies were taken.

Development and translation of thiometallate sulfide donors using a porcine model of coronary occlusion and reperfusion.

Sulfide-releasing compounds reduce reperfusion injury by decreasing mitochondria-derived reactive oxygen species production. We previously characterised ammonium tetrathiomolybdate (ATTM), a clinically used copper chelator, as a sulfide donor in rodents. Here we assessed translation to large mammals prior to clinical testing. In healthy pigs an intravenous ATTM dose escalation revealed a reproducible pharmacokinetic/pharmacodynamic (PK/PD) relationship with minimal adverse clinical or biochemical events. In a myocardial infarction (1-h occlusion of the left anterior descending coronary artery)-reperfusion model, intravenous ATTM or saline was commenced just prior to reperfusion. ATTM protected the heart (24-h histological examination) in a drug-exposure-dependent manner (r2 = 0.58, p < 0.05). Blood troponin T levels were significantly (p < 0.05) lower in ATTM-treated animals while myocardial glutathione peroxidase activity, an antioxidant selenoprotein, was elevated (p < 0.05). Overall, our study represents a significant advance in the development of sulfides as therapeutics and underlines the potential of ATTM as a novel adjunct therapy for reperfusion injury. Mechanistically, our study suggests that modulating selenoprotein activity could represent an additional mode of action of sulfide-releasing drugs.

Growth capacity of a Wharton's Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets.

Background: Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton's Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy. Methods: Sixteen four-week-old Landrace pigs were randomized to undergo supravalvar Main Pulmonary Artery (MPA) replacement with either unseeded or WJ-MSCs-seeded Small Intestinal Submucosa-derived grafts. Animals were followed up for 6 months by clinical examinations and cardiac imaging. At termination, sections of MPAs were assessed by macroscopic inspection, histology and fluorescent immunohistochemistry. Results: Data collected at 6 months follow up showed no sign of graft thrombosis or calcification. The explanted main pulmonary arteries demonstrated a significantly higher degree of cellular organization and elastin content in the WJ-MSCs seeded grafts compared to the acellular counterparts. Transthoracic echocardiography and cardiovascular magnetic resonance confirmed the superior growth and remodelling of the WJ-MSCs seeded conduit compared to the unseeded. Conclusion: Our findings indicate that the addition of WJ-MSCs to the acellular scaffold can upgrade the material, converting it into a biologically active tissue, with the potential to grow, repair and remodel the RVOT.

Intramuscular injection of alfaxalone in combination with butorphanol for sedation in cats.

OBJECTIVE: To assess quality of sedation following intramuscular (IM) injection of two doses of alfaxalone in combination with butorphanol in cats. STUDY DESIGN: Prospective, randomized, 'blinded' clinical study. ANIMALS: A total of 38 cats undergoing diagnostic imaging or noninvasive procedures. METHODS: Cats were allocated randomly to be administered butorphanol 0.2 mg kg-1 combined with alfaxalone 2 mg kg-1 (group AB2) or 5 mg kg-1 (group AB5) IM. If sedation was inadequate, alfaxalone 2 mg kg-1 IM was administered and cats were excluded from further analysis. Temperament [1 (friendly) to 5 (aggressive)], response to injection, sedation score at 2, 6, 8, 15, 20, 30, 40, 50 and 60 minutes, overall sedation quality scored after data collection [1 (excellent) to 4 (inadequate)] and recovery quality were assessed. Heart rate (HR), respiratory rate (fR) and arterial haemoglobin saturation (SpO2) were recorded every 5 minutes. Groups were compared using t tests and Mann-Whitney U tests. Sedation was analysed using two-way anova, and additional alfaxalone using Fisher's exact test (p < 0.05). RESULTS: Groups were similar for sex, age, body mass and response to injection. Temperament score was lower in group AB2 [2 (1-3)] compared to AB5 [3 (1-5)] (p = 0.006). Group AB5 had better sedation at 6, 8, 20 and 30 minutes and overall sedation quality was better in AB5 [1 (1-3)], compared to AB2 [3 (1-4)] (p = 0.0001). Additional alfaxalone was required for 11 cats in AB2 and two in AB5 (p = 0.005). Recovery quality, HR, fR and SpO2 were similar. Seven cats required oxygen supplementation. Complete recovery times were shorter in AB2 (81.8 ± 24.3 versus 126.6 ± 33.3 minutes; p = 0.009). Twitching was the most common adverse event. CONCLUSIONS AND CLINICAL RELEVANCE: In combination with butorphanol, IM alfaxalone at 5 mg kg-1 provided better quality sedation than 2 mg kg-1. Monitoring of SpO2 is recommended.

Alfaxalone for maintenance of anaesthesia in ponies undergoing field castration: continuous infusion compared with intravenous boluses.

OBJECTIVE: To compare alfaxalone as continuous intravenous (IV) infusion with intermittent IV injections for maintenance of anaesthesia in ponies undergoing castration. STUDY DESIGN: Prospective, randomized, 'blinded' clinical study. ANIMALS: A group of 33 entire male Welsh ponies undergoing field castration. METHODS: After preanaesthetic medication with IV detomidine (10 µg kg-1) and butorphanol (0.05 mg kg-1), anaesthesia was induced with IV diazepam (0.05 mg kg-1) followed by alfaxalone (1 mg kg-1). After random allocation, anaesthesia was maintained with either IV alfaxalone 2 mg kg-1 hour-1 (group A; n = 16) or saline administered at equal volume (group S; n = 17). When necessary, additional alfaxalone (0.2 mg kg-1) was administered IV. Ponies were breathing room air. Using simple descriptive scales, surgical conditions and anaesthesia recovery were scored. Total amount of alfaxalone, ponies requiring additional alfaxalone and time to administration, time from induction to end of infusion and end of infusion to standing were noted. Indirect arterial blood pressure, pulse and respiratory rates, end-expiratory carbon dioxide partial pressure and arterial haemoglobin oxygen saturation were recorded every 5 minutes. Data were analysed using Student t, Mann-Whitney U and chi-square tests, where appropriate (p < 0.05). RESULTS: Total amount of alfaxalone administered after induction of anaesthesia (0.75 ± 0.27 versus 0.17 ± 0.23 mg kg-1; p < 0.0001) and time to standing (14.8 ± 4 versus 11.6 ± 4 minutes; p = 0.044) were higher in group A compared to group S. Ponies requiring additional alfaxalone boluses [four (group A) versus seven (group S)] and other measured variables were similar between groups; five ponies required oxygen supplementation [three (group A) versus two (group S)]. CONCLUSION AND CLINICAL RELEVANCE: Continuous IV infusion and intermittent administration of alfaxalone provided similar anaesthesia quality and surgical conditions in ponies undergoing field castration. Less alfaxalone is required when used intermittently.

Molecular characterization of swine leukocyte antigen gene diversity in purebred Pietrain pigs.

The porcine major histocompatibility complex (MHC) harbors the highly polymorphic swine leukocyte antigen (SLA) class I and II gene clusters encoding glycoproteins that present antigenic peptides to T cells in the adaptive immune response. In Austria, the majority of commercial pigs are F 2 descendants of F 1 Large White/Landrace hybrids paired with Pietrain boars. Therefore, the repertoire of SLA alleles and haplotypes present in Pietrain pigs has an important influence on that of their descendants. In this study, we characterized the SLA class I ( SLA-1 , SLA-2 , SLA-3 ) and class II ( SLA-DRB1 , SLA-DQB1 , SLA-DQA ) genes of 27 purebred Pietrain pigs using a combination of the high-resolution sequence-based typing (SBT) method and a low-resolution (Lr) PCR-based method using allele-group, sequence-specific primers (PCR-SSP). A total of 15 class I and 13 class II haplotypes were identified in the studied cohort. The most common SLA class I haplotype Lr-43.0 ( SLA-1 *11XX- SLA-3 *04XX- SLA-2 *04XX) was identified in 11 animals with a frequency of 20%. For SLA class II, the most prevalent haplotype, Lr-0.14 [ SLA-DRB1 *0901- SLA-DQB1 *0801- SLA-DQA *03XX], was found in 14 animals with a frequency of 26%. Two class II haplotypes, tentatively designated as Lr-Pie-0.1 [ SLA-DRB1 *01XX/be01/ha04- SLA-DQB1 *05XX- SLA - DQA*blank] and Lr-Pie-0.2 [ SLA-DRB1 *06XX- SLA-DQB1 *03XX- SLA-DQA *03XX], appeared to be novel and have never been reported so far in other pig populations. We showed that SLA genotyping using PCR-SSP-based assays represents a rapid and cost-effective way to study SLA diversity in outbred commercial pigs and may facilitate the development of more effective vaccines or identification of disease-resistant pigs in the context of SLA antigens to improve overall swine health.