The use of ultrasound for noninvasive monitoring of anesthetic effects in renal ischemia-reperfusion injury.

OBJECTIVE: Compared with the use of ultrasound for noninvasive monitoring of the anesthetic sodium pentobarbital versus tribromoethanol in an animal model of renal ischemia-reperfusion injury in rats. METHODS: Adult rats were randomly assigned to a renal ischemia-reperfusion injury model, and preoperative anesthetics were administered as either sodium pentobarbital or tribromoethanol. Color Doppler ultrasound and spectral Doppler ultrasound were used to detect changes in respiratory rate and heart rate during and after the surgery, as well as measure renal hemodynamic parameters including peak systolic velocity, end-diastolic velocity, and resistance index. RESULTS: The frequency of changes in respiration and heart rate was significantly higher in the sodium pentobarbital anesthesia group compared to the tribromoethanol anesthesia group. The peak systolic velocity and end-diastolic velocity values in the sodium pentobarbital anesthesia group were significantly lower than those in the tribromoethanol group. However, the resistance index in the sodium pentobarbital group was higher than that in the tribromoethanol group. CONCLUSION: Ultrasound can be used to dynamically monitor the effects of anesthesia during the experiment, including changes in respiratory rate and heart rate, as well as semi-quantitatively monitor hemodynamic changes in the kidneys, which indirectly reflects whole-body hemodynamic changes in rats.

Comparison of cardiopulmonary effects of propofol, ketamine-propofol and isoflurane anesthesia in the domestic chicken (Gallus gallus domesticus).

OBJECTIVE: To compare the effects of propofol, ketamine-propofol and isoflurane, at similar anesthetic depth, on cardiopulmonary variables in unpremedictated chickens. STUDY DESIGN: Prospective, randomized, crossover experimental trial. ANIMALS: A total of 10 male Leghorn domestic chickens, aged 3 months and body mass 1.4-2.0 kg. METHODS: Birds were randomly assigned to each of three anesthetic protocols, 7 days apart: intravenous propofol, intravenous ketamine-propofol or isoflurane. Anesthesia was induced (indicated by loss of righting reflex and tracheal intubation) and maintained with propofol (10 mg kg-1 minute-1, then 1.1 mg kg-1 minute-1), ketamine-propofol (5 mg mL-1 ketamine and 5 mg mL-1 propofol combined; 10 mg kg-1 minute-1, then 1.1 mg kg-1 minute-1) or isoflurane [5% vaporizer setting initially, then end-tidal concentration (Fe'Iso) of 2%] for 65 minutes. Anesthesia was maintained at a similar anesthetic depth based upon positive or negative responses to toe pinch. Heart rate (HR), respiratory rate (fR), noninvasive arterial blood pressure and arterial blood gases were measured during anesthesia. Propofol or ketamine-propofol infusion rates and Fe'Iso required to prevent movement in response to a noxious stimulus and recovery times were recorded. RESULTS: Anesthesia induction dose was 9.0 ± 0.8 (mean ± SD) and 12.2 ± 0.3 mg kg-1 for propofol and ketamine-propofol, respectively. Propofol and ketamine-propofol infusion rates and Fe'Iso required to prevent movement in response to the noxious stimulus were 0.88 ± 0.14 mg kg-1 minute-1, 0.92 ± 0.14 mg kg-1 minute-1 and 1.45 ± 0.28%, respectively. Cardiopulmonary variables remained clinically acceptable, but ketamine-propofol was associated with a significantly higher HR (p = 0.0001) and lower fR (p = 0.0001). Time to extubation did not differ among treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Cardiovascular and respiratory variables were maintained within normal ranges in all treatments. Coadministration of ketamine with propofol significantly reduced the induction and maintenance dose of propofol.

The role of neuronal excitation and inhibition in the pre-Bötzinger complex on the cough reflex in the cat.

Brainstem respiratory neuronal network significantly contributes to cough motor pattern generation. Neuronal populations in the pre-Bötzinger complex (PreBötC) represent a substantial component for respiratory rhythmogenesis. We studied the role of PreBötC neuronal excitation and inhibition on mechanically induced tracheobronchial cough in 15 spontaneously breathing, pentobarbital anesthetized adult cats (35 mg/kg, iv initially). Neuronal excitation by unilateral microinjection of glutamate analog d,l-homocysteic acid resulted in mild reduction of cough abdominal electromyogram (EMG) amplitudes and very limited temporal changes of cough compared with effects on breathing (very high respiratory rate, high amplitude inspiratory bursts with a short inspiratory phase, and tonic inspiratory motor component). Mean arterial blood pressure temporarily decreased. Blocking glutamate-related neuronal excitation by bilateral microinjections of nonspecific glutamate receptor antagonist kynurenic acid reduced cough inspiratory and expiratory EMG amplitude and shortened most cough temporal characteristics similarly to breathing temporal characteristics. Respiratory rate decreased and blood pressure temporarily increased. Limiting active neuronal inhibition by unilateral and bilateral microinjections of GABAA receptor antagonist gabazine resulted in lower cough number, reduced expiratory cough efforts, and prolongation of cough temporal features and breathing phases (with lower respiratory rate). The PreBötC is important for cough motor pattern generation. Excitatory glutamatergic neurotransmission in the PreBötC is involved in control of cough intensity and patterning. GABAA receptor-related inhibition in the PreBötC strongly affects breathing and coughing phase durations in the same manner, as well as cough expiratory efforts. In conclusion, differences in effects on cough and breathing are consistent with separate control of these behaviors.NEW & NOTEWORTHY This study is the first to explore the role of the inspiratory rhythm and pattern generator, the pre-Bötzinger complex (PreBötC), in cough motor pattern formation. In the PreBötC, excitatory glutamatergic neurotransmission affects cough intensity and patterning but not rhythm, and GABAA receptor-related inhibition affects coughing and breathing phase durations similarly to each other. Our data show that the PreBötC is important for cough motor pattern generation, but cough rhythmogenesis appears to be controlled elsewhere.

Patterns of cardio-respiratory motor outputs during acute and subacute exposure to chlorpyrifos in an ex-vivo in situ preparation in rats.

While a considerable body of literature has characterized the clinical features induced by organophosphate pesticides, the field lacks scrutiny into cardio-respiratory changes in different phases of poisoning. Herein, we evaluated the impact of chlorpyrifos (CPF) and its active metabolite chlorpyrifos-oxon (CPO) on the cardiorespiratory system during acute and subacute phases of poisoning using an in situ experimental rodent model. CPF (30 mg/kg) was injected intraperitoneally to rats beforehand (24 h) whereas CPO (15 mg/kg) was added into the perfusate reservoir to evaluate the effects on the motor outputs throughout the three phases of the respiratory cycle: inspiration, post-inspiration and late expiration. Phrenic, recurrent laryngeal (RLN) and thoracic sympathetic nerve activity (tSNA) were recorded. Heart rate was derived from the electrocardiogram (ECG) and the baro- and chemo-reflexes tested. CPF and CPO led to a time-dependent change in cardiorespiratory motor outputs. In the acute phase, the CPO induced bradypnea, transiently reduced the inspiratory time (TI), and increased the amplitude of phrenic. Post-inspiratory (PI) discharge recorded from the RLN was progressively reduced while tSNA was increased. CPO significantly depressed the chemoreflex but had no effect on baroreflex. During subacute phase, CPF prolongated TI with no effect on respiratory rate. Both the RLN PI discharge, the chemoreflex and the baroreflex sympathetic gain were reduced. In addition, both CPF and CPO shifted the cardiac sympatho-vagal balance towards sympathetic dominance. Our data show that different phases of poisoning are associated with specific changes in the cardio-respiratory system and might therefore demand distinct approaches by health care providers.

Eupnea and gasping in vivo are facilitated by the activation of 5-HT2A receptors.

Eupnea and gasping in infancy depend on central nervous system (CNS) serotonin (5-hydroxytryptamine; 5-HT). Although previous in vitro preparations have provided some evidence that 5-HT acts through type 2 A receptors (5-HT2A) to facilitate eupnea and gasping, here the hypothesis addressed is that 5-HT2A receptor activation is necessary for eupnea and the proper generation of gasping in vivo. To test this, we administered 2,5-dimethoxy-4-iodoamphetamine (DOI; 0.25 mg/kg i.p.), a 5-HT2A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.25 mg/kg i.p.), a 5-HT1A agonist, or vehicle (saline) to 7-9-day-old tryptophan hydroxylase 2 knockout (TPH2-/-) mice. A second experiment assessed the effect of MDL-11,939 (MDL; 10 mg/kg i.p.), the specific 5-HT2A antagonist, or vehicle (DMSO) on the gasping of wild-type (TPH2+/+) animals. Drugs were given 15 min prior to five episodes of severe hypoxia that elicited gasping. TPH2-/- breathed more slowly but had the same V̇e and V̇e/V̇o2 compared with TPH2+/+. As previously reported, the gasping of TPH2-/- was significantly delayed (P < 0.001) and occurred at a significantly lower frequency compared with TPH2+/+ (P = 0.04). For both genotypes, DOI hastened eupneic frequency but had no effect on V̇e or V̇e/V̇o2. The gasping of TPH2-/-, although unaffected by 8-OH-DPAT, was indistinguishable from the gasping of TPH2+/+ following DOI. In TPH2+/+, application of MDL led to hypoventilation (P = 0.01), a delay in the appearance of gasping (P = 0.005), and reduced gasp frequency (P = 0.05). These data show that, in vivo, 5-HT2A receptors facilitate both eupnea and gasping. As has been shown in vitro, 5-HT2A probably promotes gasping by exciting hypoxia-resistant pacemaker neurons.NEW & NOTEWORTHY Previous in vitro studies suggest that 5-HT2A receptors contribute to eupnea and are necessary for fictive gasping. The current study shows that the impaired gasping displayed by neonatal TPH2-/- mice, deficient in CNS serotonin, is restored by 5-HT2A receptor activation. Following 5-HT2A blockade, wild-type mice hypoventilated and their gasping resembled that of TPH2-/- mice. This study shows that both eupnea and gasping in vivo rely on the activation of 5-HT2A receptors.

Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study.

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-ß (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.

The 14-day repeated-dose toxicity study of a fixed-dose combination, QXOH/levobupivacaine, via subcutaneous injection in beagle dogs.

QXOH-Levobupivacaine (LB) is a fixed-dose combination of 35-mM QXOH and 10-mM LB. It was developed for perioperative analgesia because of its long-acting analgesic effect. The purpose of this study was to evaluate the potential toxicity of QXOH-LB in beagle dogs in accordance with the Guidance on the repeated-dose toxicity published by the China Food and Drug Administration. Groups of five male and five female beagle dogs received normal saline, QXOH-LB (2, 4, and 8 mg/kg, calculated as QXOH), QXOH (2, 4, and 8 mg/kg), or LB (2 mg/kg, equals the concentration of LB in 8-mg/kg QXOH-LB group) at the volume of 1 mL/kg once per day for 14 days through subcutaneous injection. No mortality was observed. Dogs in the control group as well as animals treated with 2-mg/kg QXOH or QXOH-LB exhibited normal behaviors. Clinical signs of toxicity in dogs treated with 4 and 8 mg/kg of QXOH or QXOH-LB included decreased activity, unsteady gait, jerks, tremors, vocalization, emesis, ataxia, lateral/sternal recumbency, deep/rapid respiration, and gasping. Additionally, neurological function was found to be affected by QXOH and QXOH-LB at the doses of 4 and 8 mg/kg. All clinical signs were recovered within 24 h. The no-observed-adverse-effect level of QXOH and QXOH-LB was considered to be 2 mg/kg. Toxicokinetic data showed that exposure to QXOH and LB increased as QXOH-LB doses were increased from 4 to 8 mg/kg. There was no evidence of drug accumulation or any effect of gender.

The effects of zinc amino acid complex on biomarkers of gut integrity, inflammation, and metabolism in heat-stressed ruminants.

Study objectives were to evaluate the effects of replacing 40 mg/kg of dietary Zn from Zn sulfate (ZS) with Zn amino acid complex (ZA; Zinpro Corporation, Eden Prairie, MN) on inflammation and intestinal integrity in heat-stressed and pair-fed (PF) ruminants. Forty Holstein steers (173.6 ± 4.9 kg) were randomly assigned to 1 of 5 dietary-environmental treatments: (1) thermoneutral (TN) ad libitum with 75 mg/kg of dry matter (DM) ZS (ZSCON); (2) TN pair-fed with 75 mg/kg DM ZS (ZSPF); (3) TN pair-fed with 40 mg/kg DM ZA and 35 mg/kg DM ZS (ZAPF); (4) heat stress (HS) ad libitum with 75 mg/kg DM ZS (ZSHS); and (5) HS ad libitum 40 mg/kg DM ZA and 35 mg/kg DM ZS (ZAHS). Before study initiation, calves were fed their respective diets for 21 d. Following the pre-feeding phase, steers were transferred into environmental chambers and were subjected to 2 successive experimental periods. During period 1 (5 d), all steers were fed their respective diets ad libitum and housed in TN conditions (20.2 ± 1.4°C, 30.4 ± 4.3% relative humidity). During period 2 (6 d), ZSHS and ZAHS steers were exposed to cyclical HS conditions (27.1 ± 1.5°C to 35.0 ± 2.9°C, 19.3 ± 3.5% relative humidity), whereas the ZSCON, ZSPF, and ZAPF steers remained in TN conditions and were fed ad libitum or pair-fed relative to their ZSHS and ZAHS counterparts. Overall, steers exposed to HS had markedly increased rectal temperature (0.83°C), respiration rate (26 breaths per min), and skin temperature (8.00°C) relative to TN treatments. Rectal temperature from ZAHS steers was decreased (0.24°C) on d 4 to 6 of HS relative to ZSHS steers. Regardless of diet, HS decreased DMI (18%) relative to ZSCON steers. Circulating glucose from HS and PF steers decreased (16%) relative to ZSCON steers. Heat stress and nutrient restriction increased circulating nonesterified fatty acids 2- and 3-fold, respectively, compared with ZSCON steers. Serum amyloid A increased ~2-fold in PF relative to ZSCON and HS steers. We detected no treatment effect on blood pH; however, ZAHS steers had increased HCO3 relative to ZSHS. Relative to ZSHS, ZAHS steers had increased jejunum villi height (25%), a tendency for increased ileum villi height (9%), and decreased duodenal villi width (16%). In summary, ZA supplementation has some beneficial effects on thermal indices, intestinal architecture characteristics, and biomarkers of leaky gut in heat-stressed steers, indicative of an ameliorated heat load, and thus may be a nutritional strategy to minimize negative consequences of HS.

Short- and long-term dynamics of the physiological and behavioral response to heat stress and thymol supplementation in Japanese quail.

Organisms have evolved endogenous timing systems that enable them to predict temporal changes and to coordinate complex internal processes. However, temporal dynamics of biological responses are most often ignored in fields such as dietary supplementation of farm animals exposed to artificial environmental challenges. Herein, we hypothesized that the potential for thymol (2-isopropyl-5-methylphenol) to alleviate physiological and behavioral consequences of heat stress is time-dependent on both long-term (i.e. weeks) and short-term (i.e. within day) time scales. First, during 3-weeks adult female Japanese quail (Coturnix japonica) were exposed daily to 9h of increased environmental temperature (34.2 ± 0.1 °C). Controls remained at standard temperatures (23.6 ± 0.1 °C). Simultaneously, half received thymol dietary supplementation and the other half a control basal diet. On day 4, both thymol and heat stress decreased body weight and feed intake respect to controls (basal, standard temperature). After three weeks, feed intake recovered for thymol groups. Therefore, we performed a second experiment focused on the critical first week of treatment, sampling variables three times a day. The beneficial effects of thymol supplementation were mainly observed during the morning, including prevention of high respiratory rates and reduction in the weight of droppings induced by heat stress, and increased walking under both temperatures. In summary, thymol's potential for alleviating heat stress consequences is time-dependent, and can be conceived as an emergent property resulting from the complex interplay between the dynamics of the biological response to thymol and heat stress. Findings highlight the importance of considering time-related factors when developing supplementation protocols to mitigate environmental challenges.

Thrombin action on astrocytes in the hindbrain of the rat disrupts glycemic and respiratory control.

Severe trauma can produce a postinjury "metabolic self-destruction" characterized by catabolic metabolism and hyperglycemia. The severity of the hyperglycemia is highly correlated with posttrauma morbidity and mortality. Although no mechanism has been posited to connect severe trauma with a loss of autonomic control over metabolism, traumatic injury causes other failures of autonomic function, notably, gastric stasis and ulceration ("Cushing's ulcer"), which has been connected with the generation of thrombin. Our previous studies established that proteinase-activated receptors (PAR1; "thrombin receptors") located on astrocytes in the autonomically critical nucleus of the solitary tract (NST) can modulate gastric control circuit neurons to cause gastric stasis. Hindbrain astrocytes have also been implicated as important detectors of low glucose or glucose utilization. When activated, these astrocytes communicate with hindbrain catecholamine neurons that, in turn, trigger counterregulatory responses (CRR). There may be a convergence between the effects of thrombin to derange hindbrain gastrointestinal control and the hindbrain circuitry that initiates CRR to increase glycemia in reaction to critical hypoglycemia. Our results suggest that thrombin acts within the NST to increase glycemia through an astrocyte-dependent mechanism. Blockade of purinergic gliotransmission pathways interrupted the effect of thrombin to increase glycemia. Our studies also revealed that thrombin, acting in the NST, produced a rapid, dramatic, and potentially lethal suppression of respiratory rhythm that was also a function of purinergic gliotransmission. These results suggest that the critical connection between traumatic injury and a general collapse of autonomic regulation involves thrombin action on astrocytes.

Progressive cardiorespiratory dysfunction in Kv1.1 knockout mice may provide temporal biomarkers of pending sudden unexpected death in epilepsy (SUDEP): The contribution of orexin.

OBJECTIVE: Immediately preceding sudden unexpected death in epilepsy (SUDEP), patients experienced a final generalized tonic-clonic seizure (GTCS), rapid ventilation, apnea, bradycardia, terminal apnea, and asystole. Whether a progressive pathophysiology develops and increases risk of SUDEP remains unknown. Here, we determined (a) heart rate, respiratory rate, and blood oxygen saturation (SaO2 ) in low-risk and high-risk knockout (KO) mice; and (b) whether blocking receptors for orexin, a cardiorespiratory neuromodulator, influences cardiorespiratory function mice or longevity in high-risk KO mice. METHODS: Heart rate and SaO2 were determined noninvasively with ECGenie and pulse oximetry. Respiration was determined with noninvasive airway mechanics technology. The role of orexin was determined within subject following acute treatment with a dual orexin receptor antagonist (DORA, 100 mg/kg). The number of orexin neurons in the lateral hypothalamus was determined with immunohistochemistry. RESULTS: Intermittent bradycardia was more prevalent in high-risk KO mice, an effect that may be the result of increased parasympathetic drive. High-risk KO mice had more orexin neurons in the lateral hypothalamus. Blocking of orexin receptors differentially influenced heart rate in KO, but not wild-type (WT) mice. When DORA administration increased heart rate, it also decreased heart rate variability, breathing frequency, and/or hypopnea-apnea. Blocking orexin receptors prevented the methacholine (MCh)-induced increase in breathing frequency in KO mice and reduced MCh-induced seizures, via a direct or indirect mechanism. DORA improved oxygen saturation in KO mice with intermittent hypoxia. Daily administration of DORA to high-risk KO mice increased longevity. SIGNIFICANCE: High-risk KO mice have a unique cardiorespiratory phenotype that is characterized by progressive changes in five interdependent endpoints. Blocking of orexin receptors attenuates some of these endpoints and increases longevity, supporting the notion that windows of opportunity for intervention exist in this preclinical SUDEP model.

An Automated Algorithm Incorporating Poincaré Analysis Can Quantify the Severity of Opioid-Induced Ataxic Breathing.

BACKGROUND: Opioid-induced respiratory depression (OIRD) is traditionally recognized by assessment of respiratory rate, arterial oxygen saturation, end-tidal CO2, and mental status. Although an irregular or ataxic breathing pattern is widely recognized as a manifestation of opioid effects, there is no standardized method for assessing ataxic breathing severity. The purpose of this study was to explore using a machine-learning algorithm for quantifying the severity of opioid-induced ataxic breathing. We hypothesized that domain experts would have high interrater agreement with each other and that a machine-learning algorithm would have high interrater agreement with the domain experts for ataxic breathing severity assessment. METHODS: We administered target-controlled infusions of propofol and remifentanil to 26 healthy volunteers to simulate light sleep and OIRD. Respiration data were collected from respiratory inductance plethysmography (RIP) bands and an intranasal pressure transducer. Three domain experts quantified the severity of ataxic breathing in accordance with a visual scoring template. The Krippendorff alpha, which reports the extent of interrater agreement among N raters, was used to assess agreement among the 3 domain experts. A multiclass support vector machine (SVM) was trained on a subset of the domain expert-labeled data and then used to quantify ataxic breathing severity on the remaining data. The Vanbelle kappa was used to assess the interrater agreement of the machine-learning algorithm with the grouped domain experts. The Vanbelle kappa expands on the Krippendorff alpha by isolating a single rater-in this case, the machine-learning algorithm-and comparing it to a group of raters. Acceptance criteria for both statistical measures were set at >0.8. The SVM was trained and tested using 2 sensor inputs for the breath marks: RIP and intranasal pressure. RESULTS: Krippendorff alpha was 0.93 (95% confidence interval [CI], 0.91-0.95) for the 3 domain experts. Vanbelle kappa was 0.98 (95% CI, 0.96-0.99) for the RIP SVM and 0.96 (0.92-0.98) for the intranasal pressure SVM compared to the domain experts. CONCLUSIONS: We concluded it may be feasible for a machine-learning algorithm to quantify ataxic breathing severity in a manner consistent with a panel of domain experts. This methodology may be helpful in conjunction with traditional measures to identify patients experiencing OIRD.

Phasic inhibition as a mechanism for generation of rapid respiratory rhythms.

Central neural networks operate continuously throughout life to control respiration, yet mechanisms regulating ventilatory frequency are poorly understood. Inspiration is generated by the pre-Bötzinger complex of the ventrolateral medulla, where it is thought that excitation increases inspiratory frequency and inhibition causes apnea. To test this model, we used an in vitro optogenetic approach to stimulate select populations of hindbrain neurons and characterize how they modulate frequency. Unexpectedly, we found that inhibition was required for increases in frequency caused by stimulation of Phox2b-lineage, putative CO2-chemosensitive neurons. As a mechanistic explanation for inhibition-dependent increases in frequency, we found that phasic stimulation of inhibitory neurons can increase inspiratory frequency via postinhibitory rebound. We present evidence that Phox2b-mediated increases in frequency are caused by rebound excitation following an inhibitory synaptic volley relayed by expiration. Thus, although it is widely thought that inhibition between inspiration and expiration simply prevents activity in the antagonistic phase, we instead propose a model whereby inhibitory coupling via postinhibitory rebound excitation actually generates fast modes of inspiration.

Ameliorative effects of L-glutamine on haematological parameters in heat-stressed Red Sokoto goats.

The aim of the study was to evaluate haematological responses in Red Sokoto goats (RSGs) administered with L-glutamine during the hot-dry season. Experimental animals included 28 clinically healthy RSGs divided into treated group (n = 14); each administered L-glutamine at 0.2 g/kg body weight, dissolved in 10 mL distilled water, and control group (n = 14); each administered 10 mL distilled water, per os once daily for 21 days. The ambient temperature and relative humidity recorded daily for 4 weeks were used to calculate the temperature-humidity index. Three millilitres of blood sample was collected from each goat by jugular venipuncture for haematology, while rectal temperature (RT), heart rate (HR) and respiratory rate (RR) were also measured once weekly at weeks 0 (before), 1, 2, 3 (during) and 4 (after L-glutamine administration). The haematological, RT, HR and RR data obtained weekly were analysed using repeated-measures one-way ANOVA, followed by Tukey's post-hoc test to evaluate differences between periods, and between treated and control groups. The PCV, haemoglobin concentration and RBC count were higher (P < 0.05) in the treated group compared to the control group during the period of L-glutamine administration. These differences were sustained till week 4. Beginning from week 1 of the study, the total leucocyte count in treated group (10.10 ± 0.25 × 103/µL) was higher (P < 0.05) than the count in control group (7.23 ± 0.41 × 103/µL), this trend was also maintained throughout the study. The neutrophil:lymphocyte ratio during weeks 3 and 4 of the experiment was lower (P < 0.05) in the treated compared to the control group. RT was lower (P < 0.05) in treated group than the control group. In conclusion, L-glutamine administration ameliorated the adverse effects of heat stress on the haematological parameters in RSGs during the hot-dry season.

Immobilization quality and cardiopulmonary effects of etorphine alone compared with etorphine-azaperone in blesbok (Damaliscus pygargus phillipsi).

OBJECTIVE: To evaluate the immobilization quality and cardiopulmonary effects of etorphine alone compared with etorphine-azaperone in blesbok (Damaliscus pygargus phillipsi). STUDY DESIGN: Blinded, randomized, crossover design. ANIMALS: A total of 12 boma-habituated female blesbok weighing [mean ± standard deviation (SD)] 57.5 ± 2.5 kg. METHODS: Each animal was administered etorphine (0.09 mg kg-1) or etorphine-azaperone (0.09 mg kg-1; 0.35 mg kg-1) intramuscularly with 1-week intertreatment washout period. Time to first sign of altered state of consciousness and immobilization time were recorded. Physiological variables were recorded, arterial blood samples were taken during a 40-minute immobilization period, and naltrexone (mean ± SD: 1.83 ± 0.06 mg kg-1) was intravenously administered. Recovery times were documented, and induction, immobilization and recovery were subjectively scored. Statistical analyses were performed; p < 0.05 was significant. RESULTS: No difference was observed in time to first sign, immobilization time and recovery times between treatments. Time to head up was longer with etorphine-azaperone (0.5 ± 0.2 versus 0.4 ± 0.2 minutes; p = 0.015). Etorphine caused higher arterial blood pressures (mean: 131 ± 17 versus 110 ± 11 mmHg, p < 0.0001), pH, rectal temperature and arterial oxygen partial pressure (59.2 ± 7.7 versus 42.2 ± 9.8 mmHg), but lower heart (p = 0.002) and respiratory rates (p = 0.01). Etorphine-azaperone combination led to greater impairment of ventilatory function, with higher end-tidal carbon dioxide (p < 0.0001) and arterial partial pressure of carbon dioxide (58.0 ± 4.5 versus 48.1 ± 5.1 mmHg). Immobilization quality was greater with etorphine-azaperone than with etorphine alone (median scores: 4 versus 3; p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: Both treatments provided satisfactory immobilization of blesbok; however, in addition to a deeper level of immobilization, etorphine-azaperone caused greater ventilatory impairment. Oxygen supplementation is recommended with both treatments.

Comparison of sedative and some cardiopulmonary effects of intramuscular medetomidine or medetomidine-tramadol in dogs.

OBJECTIVE: To evaluate the clinical and physiologic effects of intramuscular (IM) administration of medetomidine with and without tramadol in dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: A group of eight mixed breed dogs of both sexes, aged 1-2 years, weighing 16.0 ± 0.6 kg. METHODS: Each dog was studied twice at ≥1 week interval. Medetomidine (5 µg kg-1; treatment M) was administered IM alone or with tramadol (4 mg kg-1; treatment MT). Sedation was scored by a system that included vocalization, posture, appearance, interactive behaviors, resistance to restraint and response to noise. Times from drug administration to ataxia, impaired walking, head drop, sternal and lateral position and standing were recorded. Sedation score, heart rate, respiratory rate, rectal temperature, end-tidal carbon dioxide (Pe'CO2), hemoglobin oxygen saturation and mean noninvasive blood pressure were recorded and compared 15 minutes before and 15, 30 and 45 minutes after drug administration. RESULTS: Dogs administered MT had higher sedation scores than dogs administered M at 30 and 45 minutes after drug administration (p < 0.05). Times to ataxia, impaired walking, head drop and sternal recumbency were not different between the treatments. Time to lateral recumbency was longer in M than in MT (21.1 ± 1.0 versus 17.6 ± 0.7 minutes, respectively; p < 0.05). Time to standing was longer in MT than in M (67.9 ± 1.4 versus 54.5 ± 1.9 minutes, respectively; p < 0.001). Measured physiological variables did not differ between the treatments, with the exception of Pe'CO2, which was higher in MT than in M at all post-treatment evaluation times (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Tramadol combined with medetomidine resulted in greater sedation scores (deeper sedation) than medetomidine alone in dogs, and minimal adverse changes in the physiologic variables were measured.

Evaluation of the sedative and clinical effects of xylazine, detomidine, medetomidine and dexmedetomidine in miniature donkeys.

Aim: To evaluate the sedative and clinical effects of I/V xylazine, detomidine, medetomidine and dexmedetomidine in miniature donkeys.Methods: Seven clinically healthy, male adult miniature donkeys with a mean age of 6 years and weight of 105 kg, were assigned to five I/V treatments in a randomised, cross-over design. They received either 1.1 mg/kg xylazine, 20 µg/kg detomidine, 10 µg/kg medetomidine, 5 µg/kg dexmedetomidine or saline, with a washout period of ≥7 days. The degree of sedation was scored using a 4-point scale by three observers, and heart rate (HR), respiration rate (RR), rectal temperature and capillary refill time (CRT) were recorded immediately before and 5, 10, 15, 30, 60, 90 and 120 minutes after drug administration.Results: All saline-treated donkeys showed no sedation at any time, whereas the donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine had mild or moderate sedation between 5 and 60 minutes after treatment, and no sedation after 90 minutes. All animals recovered from sedation without complication within 2 hours. The mean HR and RR of saline-treated donkeys did not change between 0 and 120 minutes after administration, but the mean HR and RR of donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine declined between 5 and 60 minutes after drug administration. The mean rectal temperature of all treated donkeys did not change between 0 and 120 minutes after administration. The CRT for all donkeys was ≤2 seconds at all times following each treatment.Conclusions and clinical relevance: Administration of xylazine at 1.1 mg/kg, detomidine at 20 µg/kg, medetomidine at 10 µg/kg and dexmedetomidine at 5 µg/kg resulted in similar sedation in miniature donkeys. Therefore any of the studied drugs could be used for sedation in healthy miniature donkeys.

Anesthetic effects of AQUI-S 20E® (eugenol) on the afferent neural activity of the oyster toadfish (Opsanus tau).

Anesthesia is used to sedate aquatic animals during transportation or to immobilize them for surgery. However, most studies have focused on the behavioral effects of induction and recovery, without addressing the effect of anesthetic on neural activity. This study investigated the neural response of anterior lateral line afferent fibers in the oyster toadfish, Opsanus tau, during exposure to incremental increases of AQUI-S 20E (0.001-0.006%), to determine if eugenol (the active ingredient of AQUI-S 20E) influences neural activity of the fish lateral line system. Ventilation rate significantly decreased following AQUI-S 20E exposure with the surgical plane of anesthesia reached at 0.003%, characterized by shallow ventilation, equilibrium loss, and no response to tactile stimuli. Spontaneous and evoked firing rates of anterior lateral line fibers also significantly decreased following exposure, although the effect was transitory as neural activity recovered in the majority of fibers (70%) within 30 min of anesthetic withdrawal. While AQUI-S 20E proved effective in inducing the surgical plane of anesthesia without compromising survival, it is not recommended for acute neural preparations due to its depression of neural activity. However, the depression of lateral line sensitivity at low concentrations could play a role in reducing the stress response during fish transport.

Chromium supplementation improves glucose metabolism and vaginal temperature regulation in Girolando cows under heat stress conditions in a climatic chamber.

This study aimed to evaluate chromium supplementation on productive, reproductive, and metabolic parameters at lactating Girolando cows subjected to heat stress conditions in a climatic chamber. Thirty-six lactating Girolando cows were subjected to two sequential trials. In trial 1 (thermoneutral environment), the effect of chromium supplementation was evaluated (0 vs. 0.50 mg/kg of dry matter). In trial 2, the cows were fed the same diets, but they were divided into three environmental conditions: heat stress conditions in climatic chamber, fed ad libitum (HS); thermoneutral environment, fed ad libitum (TN); and thermoneutral environment, pair-fed (PF). In thermoneutral conditions, chromium supplementation did not affect productive or metabolic parameters, although supplemented cows had lower viability of oocytes (65.11 ± 0.08% vs. 76.86 ± 0.08%). During heat stress, chromium supplementation lowered plasma glucose levels (61.17 ± 1.90 vs. 67.11 ± 1.90 mg/dL), and increased the insulin:glucose ratio (0.39 ± 0.04 vs. 0.27 ± 0.04). Cows fed the control diet in the HS group had higher vaginal temperature values (39.40 ± 0.10 °C) than the cows in the TN group and PF group (38.89 ± 0.10 °C and 38.85 ± 0.11 °C, respectively). However, supplemented cows heat-stressed maintained the same vaginal temperature as cows in thermoneutral conditions. In conclusion, chromium supplementation improved glucose metabolism and prevented body temperature increases under heat stress conditions.

SEDATIVE, CARDIORESPIRATORY, AND THERMOREGULATORY EFFECTS OF ALFAXALONE ON BUDGERIGARS (MELOPSITTACUS UNDULATUS).

Alfaxalone is a neurosteroid anesthetic agent that has been extensively used in both human and veterinary medicine for more than 50 yr. Previous studies involving avian species demonstrated various dose ranges and multiple routes of administration. The aim of this study was to evaluate the short-term sedative, cardiorespiratory, and thermoregulatory effects of an intramuscular injection of alfaxalone on budgerigars (Melopsittacus undulatus). A crossover study was performed with a sample size of 10 male budgerigars, previously determined to be healthy based on physical examination. Alfaxalone was administered intramuscularly at two doses: 15 and 20 mg/kg. The lower dose resulted in mild to moderate sedation for 29 ± 5 min, whereas the higher dose resulted in moderate to profound sedation for 29 ± 7 min. A statistically significant decrease in heart rate was observed 2 min after administration of alfaxalone at 15 mg/kg; however, this finding was noted to be transient. A statistically significant decrease in respiratory rate was observed at 6 and 10 min after injection in both groups. Cloacal temperature measurement with a digital thermometer and eye temperature calculated from thermographic images demonstrated a decrease in body temperature over time but was not found to be statistically significant. Intramuscular use of alfaxalone proved to provide short-term sedation in budgerigars, with statistically significant but clinically mild cardiorespiratory effects. Due to a significant decrease in body temperature, active warming is recommended when using alfaxalone in budgerigars.