Cardiotoxicity of Cadmium and Its Effects on Heart Efficiency During Early and Late Chick Embryogenesis.

Cadmium (Cd) is a dangerous heavy metal that is non-degradable in the environment. Many organs can accumulate Cd and adversely affect organ function and health. Cd is considered as a teratogenic and embryotoxic agent. This study aims to evaluate the teratogenicity of Cd at concentrations lesser than the permissible and its effects on the heart during chick embryogenesis. Fertilized eggs of the chick Gallus domesticus were divided into; control, saline injected and four experimental groups injected with single doses of 5, 25, 50 or 75 µM of CdCl2. Histological observations of the heart before hatching and the cardiomyocytes after hatching were recorded. Morphometric measurements of heart chambers were achieved at 3, 4 and 6 days of incubation. Electrocardiograph and respiratory rate were recorded at tenth day. Different cardiac problems had been brought on by Cd. In comparison to controls, the heart looked much larger, and in certain cases, growth retardation was seen. Degeneration in heart walls and malformations of dorsal aorta were noticed. Morphometrically, the width and wall thickness of heart chambers showed significant changes. Heart beats and respiratory rate significantly decreased compared to control. The cardiotoxic effect of Cd on heart compartments structure and function was dose dependent. One of Cd toxicity is its ability to induce cellular oxidative stress. The heart in particular is sensitive to oxidative stress. Cardiac oxidative stress might intensify heart failure and promote disease progression. Calcium is one of the components that is needed for normal heart work. Cd might interfere with calcium metabolism by removing it from the body.

Effect of oral administration of pregabalin on physiological and echocardiographic variables in healthy cats.

OBJECTIVES: The aim of this study was to evaluate the efficacy of a single dose of oral pregabalin (PGB) for sedation and its impact on physiological and echocardiographic variables in healthy cats. METHODS: This study was a randomised, blinded, crossover trial. Eight cats were randomly assigned to receive PGB or placebo, with a 1-week washout period between each administration. Cats in the treatment group received oral PGB at varying doses (low dose: 2.5 mg/kg, medium dose: 5 mg/kg, high dose: 10 mg/kg). Systolic blood pressure (SBP), pulse rate (PR), respiratory rate (RR) and sedation score were measured at intervals of 30 mins after administration. Echocardiography was performed 120 mins after administration. RESULTS: Oral administration of PGB 2.5 mg/kg and 5 mg/kg significantly increased sedation scores starting at 150 mins, while 10 mg/kg PGB showed a significant increase in sedation scores starting at 120 mins compared with placebo. PGB 5 mg/kg and 10 mg/kg resulted in a significant reduction in SBP compared with placebo, with minimal impact on PR and RR. In addition, PGB 10 mg/kg resulted in significant changes in the peak velocity of late diastolic transmitral flow (A) and the ratio of peak velocity of early diastolic transmitral flow and A; however, these changes were of marginal clinical significance. CONCLUSIONS AND RELEVANCE: A single dose of oral PGB could cause mild to moderate sedation. Hypotension was more prevalent in the PGB 5 mg/kg and 10 mg/kg groups among the majority of cats, but it was less frequently observed in the PGB 2.5 mg/kg group.

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.

Potentiation of the depressant effect of alcohol by flunitrazepam in rats: an electrocorticographic, respiratory and electrocardiographic study.

Alcohol, a widely commercialized psychotropic drug, and the benzodiazepine Flunitrazepam, an anxiolytic widely prescribed for patients with anxiety and insomnia problems, are well known drugs and both act on the central nervous system. The misuse and the association of these two drugs are public health concerns in several countries and could cause momentary, long-lasting and even lethal neurophysiological problems due to the potentiation of their adverse effects in synergy. The present study observed the result of the association of these drugs on electrophysiological responses in the brain, heart, and respiratory rate in Wistar rats. 8 experimental groups were determined: control, one alcohol group (20% at a dose of 1 ml/100 g VO), three Flunitrazepam groups (doses 0.1; 0.2 and 0.3 mg/kg) and three alcohol-Flunitrazepam groups (20% at a dose of 1 ml/100 g VO of alcohol, combined with 0.1; 0.2 and 0.3 mg/kg of Flunitrazepam, respectively). The results showed that there was a more pronounced reduction in alpha and theta wave power in the alcohol-Flunitrazepam groups, a decrease in the power of beta oscillations and greater sedation. There was a progressive decrease in respiratory rate linked to the increase of Flunitrazepam dose in the alcohol-Flunitrazepam associated administration. It was observed alteration in heart rate and Q-T interval in high doses of Flunitrazepam. Therefore, we conclude that the association alcohol-Flunitrazepam presented deepening of depressant synergistic effects according to the increase in the dose of the benzodiazepine, and this could cause alterations in low frequency brain oscillations, breathing, and hemodynamics of the patient.

Identification of tolerance levels on the cold-water coral Desmophyllum pertusum (Lophelia pertusa) from realistic exposure conditions to suspended bentonite, barite and drill cutting particles.

Cold-water coral (CWC) reefs are numerous and widespread along the Norwegian continental shelf where oil and gas industry operate. Uncertainties exist regarding their impacts from operational discharges to drilling. Effect thresholds obtained from near-realistic exposure of suspended particle concentrations for use in coral risk modeling are particularly needed. Here, nubbins of Desmophyllum pertusum (Lophelia pertusa) were exposed shortly (5 days, 4h repeated pulses) to suspended particles (bentonite BE; barite BA, and drill cuttings DC) in the range of ~ 4 to ~ 60 mg.l-1 (actual concentration). Physiological responses (respiration rate, growth rate, mucus-related particulate organic carbon OC and particulate organic nitrogen ON) and polyp mortality were then measured 2 and 6 weeks post-exposure to assess long-term effects. Respiration and growth rates were not significantly different in any of the treatments tested compared to control. OC production was not affected in any treatment, but a significant increase of OC:ON in mucus produced by BE-exposed (23 and 48 mg.l-1) corals was revealed 2 weeks after exposure. Polyp mortality increased significantly at the two highest DC doses (19 and 49 mg.l-1) 2 and 6 weeks post-exposure but no significant difference was observed in any of the other treatments compared to the control. These findings are adding new knowledge on coral resilience to short realistic exposure of suspended drill particles and indicate overall a risk for long-term effects at a threshold of ~20 mg.l-1.

The therapeutic efficacy of quercetin in combination with antiviral drugs in hospitalized COVID-19 patients: A randomized controlled trial.

In this study, the therapeutic efficacy of quercetin in combination with remdesivir and favipiravir, were evaluated in severe hospitalized COVID-19 patients. Our main objective was to assess the ability of quercetin for preventing the progression of the disease into critical phase, and reducing the levels of inflammatory markers related to SARS-Cov-2 pathogenesis. Through an open-label clinical trial, 60 severe cases were randomly divided into control and intervention groups. During a 7-day period, patients in the control group received antivirals, i.e., remdesivir or favipiravir, while the intervention group was treated with 1000 mg of quercetin daily in addition to the antiviral drugs. According to the results, taking quercetin was significantly associated with partial earlier discharge and reduced serum levels of ALP, q-CRP, and LDH in the intervention group. Furthermore, although the values were in normal range, the statistical outputs showed significant increase in hemoglobin level and respiratory rate in patients who were taking quercetin. Based on our observations, quercetin is safe and effective in lowering the serum levels of ALP, q-CRP, and LDH as critical markers involved in COVID-19 severity. However, according to the non-significant borderline results in comparing the mortality, the ICU-admission rate, and the duration of ICU-admission, further studies can be helpful to compensate the limitations of our study and clarify the therapeutic potential of quercetin in COVID-19 treatments.

Evaluation of acute cardiorespiratory and hemodynamic changes in perioperative intravenous antimicrobial applications in cats / [Avaliação das alterações cardiorespiratórias e hemodinâmicas agudas em aplicações pré-operatórias de antimicrobianos, pela via intravenosa, em gatos]

The metabolic peculiarities of felines favor an intoxication. Fifty healthy female cats were divided into five groups: PG (placebo group), G2 (cefazolin), G3 (ceftriaxone), G4 (enrofloxacin) and G5 (ampicillin) were used. The parameters evaluated were: total expired carbon dioxide (ETCO2), oxygen saturation in hemoglobin (SpO2), heart rate (HR), respiratory rate (RR), body temperature (BT), systolic, mean and diastolic blood pressure (SBP, mBP and DBP) by invasive method, at T0, 5 (T5), 10 (T10), 15 (T15), 20 (T20), 25 (T25) and 30 (T30) minutes after administration of the treatments. HR presented reduction in G2 compared to PG at all times, except T20, and in G4, T25 and T30 were lower than the T0 values (P<0.05). BT showed increase in the G3 at T0 and T5 and all groups showed reduction in the values of BT relative to T0 (P<0.05). ETCO2 increased in G2 and G5 at all times compared to PG (P<0.05) and there were no differences among the times within each group. It was concluded that ceftriaxone is safer for the prophylactic antimicrobial use in cats, however the other antimicrobials are also indicated, because all the parameters, in all groups, basically did not change over the study and when this occurs it remains in reference interval.(AU)

As peculiaridades metabólicas dos felinos favorecem quadro de intoxicação. Foram utilizadas 50 gatas saudáveis, que foram divididas em cinco grupos: GP (grupo placebo), G2 (grupo cefazolina), G3 (grupo ceftriaxona), G4 (grupo enrofloxacina) e G5 (grupo ampicilina). Os seguintes parâmetros foram avaliados: dióxido de carbono expirado (ETCO2), saturação de oxigênio na hemoglobina (SpO2), frequência cardíaca (FC), frequência respiratória (FR), temperatura corporal (T°C), pressão arterial sistólica,média e diastólica (PAS, PAM e PAD), pelo método invasivo, em 0 (T0), 5 (T5), 10 (T10), 15 (T15), 20 (T20), 25 (T25) e 30 (T30) minutos após a administração dos tratamentos. A FC apresentou redução no G2 em relação ao GP em todos os momentos, exceto no T20, e, no G4, o T25 e o T30 foram inferiores aos valores do T0 (P<0,05). A T°C apresentou aumento no G3 no T0 e no T5, e todos os grupos apresentaram redução nos valores da T°C em relação ao T0 (P<0,05). O ETCO2 apresentou aumento no G2 e no G5, em todos os momentos, em relação ao GP (P<0,05). Concluiu-se que a ceftriaxona é mais segura para uso profilático em gatos, entretanto os outros antibióticos também são recomendados, pois todos os parâmetros praticamente não se modificaram e, quando alterados, mantiveram-se dentro dos padrões de referência.(AU)

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.

Caffeine reverses the unconsciousness produced by light anesthesia in the continued presence of isoflurane in rats.

Currently no drugs are employed clinically to reverse the unconsciousness induced by general anesthetics. Our previous studies showed that caffeine, when given near the end of an anesthesia session, accelerated emergence from isoflurane anesthesia, likely caused by caffeine's ability to elevate intracellular cAMP levels and to block adenosine receptors. These earlier studies showed that caffeine did not rouse either rats or humans from deep anesthesia (≥ 1 minimum alveolar concentration, MAC). In this current crossover study, we examined whether caffeine reversed the unconsciousness produced by light anesthesia (< 1 MAC) in the continued presence of isoflurane. The primary endpoint of this study was to measure isoflurane levels at the time of recovery of righting reflex, which was a proxy for consciousness. Rats were deeply anesthetized with 2% isoflurane (~1.5 MAC) for 20 minutes. Subsequently, isoflurane was reduced to 1.2% for 10 minutes, then by 0.2% every 10 min; animals were monitored until the recovery of righting reflex occurred, in the continued presence of isoflurane. Respiration rate, heart rate and electroencephalogram (EEG) were monitored. Our results show that caffeine-treated rats recovered their righting reflex at a significantly higher inspired isoflurane concentration, corresponding to light anesthesia, than the same rats treated with saline (control). Respiration rate and heart rate increased initially after caffeine injection but were then unchanged for the rest of the anesthesia session. Deep anesthesia is correlated with burst suppression in EEG recordings. Our data showed that caffeine transiently reduced the burst suppression time produced by deep anesthesia, suggesting that caffeine altered neuronal circuit function but not to a point where it caused arousal. In contrast, under light anesthesia, caffeine shifted the EEG power to high frequency beta and gamma bands. These data suggest that caffeine may represent a clinically viable drug to reverse the unconsciousness produced by light anesthesia.

Modulation of mitochondrial respiration rate and calcium-induced swelling by new cromakalim analogues.

A cellular model of cardiomyocytes (H9c2 cell line) and mitochondria isolated from mouse liver were used to understand the drug action of BPDZ490 and BPDZ711, two benzopyran analogues of the reference potassium channel opener cromakalim, on mitochondrial respiratory parameters and swelling, by comparing their effects with those of the parent compound cromakalim. For these three compounds, the oxygen consumption rate (OCR) was determined by high-resolution respirometry (HRR) and their impact on adenosine triphosphate (ATP) production and calcium-induced mitochondrial swelling was investigated. Cromakalim did not modify neither the OCR of H9c2 cells and the ATP production nor the Ca-induced swelling. By contrast, the cromakalim analogue BPDZ490 (1) induced a strong increase of OCR, while the other benzopyran analogue BPDZ711 (2) caused a marked slowdown. For both compounds, 1 displayed a biphasic behavior while 2 still showed an inhibitory effect. Both compounds 1 and 2 were also found to decrease the ATP synthesis, with pronounced effect for 2, while cromakalim remained without effect. Overall, these results indicate that cromakalim, as parent molecule, does not induce per se any direct effect on mitochondrial respiratory function neither on whole cells nor on isolated mitochondria whereas both benzopyran analogues 1 and 2 display totally opposite behavior profiles, suggesting that compound 1, by increasing the maximal respiration capacity, might behave as a mild uncoupling agent and compound 2 is taken as an inhibitor of the mitochondrial electron-transfer chain.

Effects of maternal protein restriction on central and peripheral renin-angiotensin systems in male rat offspring.

AIMS: We investigated the involvement of the renin angiotensin system (RAS) on the cardiorespiratory control in rats from dams fed with a low-protein diet. MAIN METHODS: Male offspring were obtained from dams fed a normoprotein diet (NP, 17% casein) and low-protein diet (LP, 8% casein) during pregnancy and lactation. Direct measurements of arterial pressure (AP), heart rate (HR) and respiratory frequency (RF) were recorded in awake 90-day-old at resting and after losartan potassium through either intracerebroventricular (ICV) microinjections or intravenous (IV) administration. Cardiovascular variability was evaluated by spectral analysis. Peripheral chemoreflex sensitivity was assessed through the potassium cyanide (KCN; 40 µg/0.1 ml/rat, IV). Gene expression was evaluated by qPCR, and MAPK (Mitogen Activated Protein Kinase) expression was evaluated by western blot. KEY FINDINGS: The LP offspring had higher mean AP (MAP) and RF than NP offspring. In the spectral analysis, the LP rats also showed higher low frequency of systolic AP (NP: 2.7 ± 0.3 vs. LP: 5.0 ± 1.0 mmHg). After ICV losartan, MAP and RF in LP rats remained higher than those in NP rats, but without changes in HR. The peripheral chemoreflex was similar between the groups. LP group had lower gene expression of Rac1 (Ras-related C3 botulinum toxin substrate 1) (NP: 1.13 ± 0.06 vs. LP: 0.88 ± 0.08). Peripherally, LP rats had larger delta of MAP after IV losartan (NP: -9.8 ± 2 vs. LP: -23 ± 6 mmHg), without changes in HR and RF. SIGNIFICANCE: In rats, the RAS participates peripherally, but not centrally, in the maintenance of arterial hypertension in male offspring induced by maternal protein restriction.

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.

Pharmacokinetics, sedation and hemodynamic changes following the administration of oral transmucosal detomidine gel in cats.

OBJECTIVES: The aim of this study was to describe the pharmacokinetics of oral transmucosal (OTM) detomidine gel in healthy cats and assess its effects on sedation and hemodynamic variables. METHODS: Eight adult cats weighing 4.12 kg ± 0.72 received 4 mg/m2 detomidine gel onto the buccal mucosa. Level of sedation, heart rate (HR), blood pressure (BP) and respiratory rate (f R) were assessed at predetermined intervals following administration. Blood samples for plasma detomidine concentrations and venous blood gas variables were collected from a medial saphenous catheter. Plasma detomidine concentrations were analyzed using ultra-high-pressure liquid chromatography with mass spectrometry detection, and pharmacokinetic estimates were obtained with compartmental methods. Data were analyzed using ANOVA and paired t-test or appropriate non-parametric tests. RESULTS: Sedation occurred in all cats, and was increased from baseline at 30 mins (P <0.001). Decreases in HR occurred from 15-60 mins, ranging from 140 to 165 beats per min (P <0.001). Blood glucose increased from 101 ± 12 mg/dl to 168 ± 27.3 mg/dl at 60 mins (P = 0.004). Systolic blood pressure decreased from baseline (139 ± 14.8 mmHg) to 103 ± 23.0 mmHg at 60 mins (P = 0.023). All changes abated by 120 mins. Emesis occurred in 7/7 cats within 2 mins of gel administration. Geometric mean (coefficient of variation) for clearance was 220.7 ml/min/kg (35.3 ml/min/kg), volume of distribution was 14.9 l/kg (39.9 l/kg) (both a function of bioavailability) and elimination half-life was 46.9 mins (16.0 mins). Maximum plasma concentrations of 10.5 ng/ml (35.5 ng/ml) detomidine occurred at 36.9 mins (21.5 mins). CONCLUSIONS AND RELEVANCE: OTM detomidine gel produced moderate sedation with minimal undesirable side effects in healthy cats, although emesis occurred in all cats. The pharmacokinetic profile supports short-term, minimally invasive sedation in this species. Further studies are warranted to assess its safety and feasibility for use in debilitated cats, or prior to general anesthesia.

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.

Dietary supplementation of artificial sweetener and capsicum oleoresin as a strategy to mitigate the negative consequences of heat stress on pig performance.

Pigs exposed to elevated ambient temperatures exhibit reduced daily gain, alterations in muscle and fat deposition, and decreased health. Negative aspects of gastrointestinal (GI) function, integrity, and permeability also occur. High-intensity sweeteners can ameliorate the negative effects of heat stress (HS) by increasing GI glucagon-like peptide-2 production while capsicum oleoresin has been shown to reduce inflammatory response. The effects of an artificial high-intensity sweetener and capsicum oleoresin (CAPS-SUC; TakTik X-Hit, Pancosma, Switzerland) on growth performance of pigs were examined. Forty-eight pigs (12 wk of age, 43.2 ± 4.3 kg) were assigned to six treatments: thermoneutral conditions (21 ± 1.1 °C; 40% to 70% relative humidity) fed ad libitum with (TN+) or without supplement (TN-), heat stress (35 ± 1 °C; 20% to 40% relative humidity) fed ad libitum with (HS+) or without supplement (HS-), and thermoneutral conditions pair-fed to HS intake with (PFTN+) or without supplement (PFTN-). Supplementation (0.1 g/kg feed) began 2 d prior to the 3-d environmental treatment period. Body weights (BWs) and blood samples were collected on days -1 and 3. Rectal temperature (RT) and respiration rate (RR) were measured thrice daily and the feed intake (FI) was recorded daily. Intestinal sections were collected for histology. Pigs in HS conditions exhibited increased RT (~1.2 °C) and RR (~2.7-fold) compared with TN and PFTN groups (P < 0.01). HS+ animals had increased RR when compared with HS- animals (P < 0.02). Heat stress decreased FI compared with TN. HS and PFTN decreased (P < 0.05) average daily gain compared with TN. Supplement did not alter the BW gain. HS and PFTN decreased (P < 0.05) Gain:Feed compared with TN during environmental treatment. Supplementation with CAPS-SUC increased Gain:Feed by 0.12 (P < 0.05). Circulating glucose concentrations tended to decrease in CAPS-SUC vs. non-supplemented HS and PFTN animals (P ≤ 0.1). Circulating insulin concentrations as well as monocyte count increased in HS compared with PFTN (P < 0.04) but did not differ from TN and likely linked to altered FI. CAPS-SUC increased basophil count (P < 0.02), irrespective of environment. Ileal villus height tended to decrease during HS and PFTN compared with TN (P < 0.08), indicating an effect of intake. Overall, CAPS-SUC supplementation increased pig feed efficiency and may improve immune response.

Effects of Standard and Sustained-release Buprenorphine on the Minimum Alveolar Concentration of Isoflurane in C57BL/6 Mice.

Both standard and sustained-release injectable formulations of buprenorphine (Bup and BupSR, respectively) are used as preemptive analgesics, potentially affecting gas anesthetic requirements. This study tested the effects of Bup and BupSR on isoflurane requirements and confirmed that buprenorphine could reduce isoflurane requirements during a laparotomy in mice. We hypothesized that both Bup and BupSR would significantly decrease the required minimum alveolar concentration (MAC) of isoflurane. C57BL/6 mice received either isotonic crystalloid fluid (control), Bup (0.1 mg/kg), or BupSR (1.2 mg/kg) subcutaneously 10 min prior to the induction of anesthesia. Each anesthetized mouse was tested at 2 isoflurane concentrations. A 300-g noxious stimulus was applied at each isoflurane concentration, alternating between hindfeet. In addition, a subset of mice underwent terminal laparotomy or 60 min of anesthesia after injection with Bup, BupSR, or saline to ensure an appropriate surgical plane of anesthesia. Mice were maintained at the lowest isoflurane concentration that resulted in 100% of mice at a surgical plane from the aforementioned MAC experiments (control, 2.0%; Bup and BupSR, 1.7%). Analysis showed that both Bup and BupSR significantly decreased isoflurane requirements by 25.5% and 14.4%, respectively. The isoflurane MAC for the control injection was 1.80% ± 0.09%; whereas Bup and BupSR decreased MAC to 1.34% ± 0.08% and 1.54% ± 0.09%, respectively. Sex was not a significantly different between the injection groups during MAC determination. All of the mice that underwent surgery achieved a surgical plane of anesthesia on the prescribed regimen and recovered normally after discontinuation of isoflurane. Lastly, heart and respiratory rates did not differ between mice that underwent surgery and those that were anesthetized only. Bup and BupSR are MAC-sparing in male and female C57BL/6 mice and can be used for effective multimodal anesthesia.

Metabolic Basis for Nonlinearity in 1,3-Dichloropropene Toxicokinetics and Use in Setting a Kinetically-derived Maximum Inhalation Exposure Concentration in Mice.

1,3-Dichloropropene (1,3-D) showed a statistically increased incidence of bronchioloalveolar adenomas in male B6C3F1 mice at 60 ppm air concentration during previous chronic inhalation testing. No tumors were observed in female mice, nor in either sex of F344 rats up to 60 ppm, the highest dose tested. Therefore, to understand if lung tumors observed in high dose male mice are due to saturation of metabolic clearance, the linearity of 1,3-D concentrations in mouse blood was investigated on day 15 of repeated nose-only inhalation exposure to 0, 10, 20, 40, 60, 90, and 120 ppm (6 h/d, 7 d/week). Additional groups were included at 20, 60, and 120 ppm for blood collection at 1.5 and 3 h of exposure and up to 25 or 40 min post-exposure to determine area-under-the-curve. The data provide multiple lines of evidence that systemic exposures to 1,3-D in the mouse become nonlinear at inhalation exposure levels of 30 ppm or above. A reduction in minute volume occurred at the highest exposure concentration. The glutathione (GSH)-dependent metabolism of 1,3-D results in significant depletion of GSH at repeated exposure levels of 30 ppm and above. This loss of GSH results in decreased metabolic clearance of this test material, with a concomitant increase of the 1,3-D isomers in circulating blood at exposure concentrations ≥30 ppm. Shifts in the ratio of cis- and trans-1,3-D also support nonlinear toxicokinetics well below 60 ppm. Based on this data, a kinetically derived maximum dose for 1,3-D in mice for repeated exposures should be at or below 30 ppm. These results support non-relevance of 1,3-D-induced benign pulmonary tumorigenicity in mice for human health risk assessment.

Sedative and physiologic effects of tiletamine-zolazepam following buccal administration in cats.

OBJECTIVES: The aim of this study was to describe the sedative and some physiological effects of tiletamine-zolazepam following buccal administration (BA) in cats. METHODS: Seven healthy spayed European shorthair cats (three males, four females) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine-zolazepam by BA: the low-dose (LD) group consisted of 5 mg/kg of each drug, and the high-dose (HD) group consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO2) were recorded at predefined intervals for the next 2 h. RESULTS: All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD groups, respectively (P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for the HD than for the LD group. No values for hemoglobin saturation <95% were observed. CONCLUSIONS AND RELEVANCE: BA of tiletamine-zolazepam at the doses studied here is a simple and effective method for chemical restraint in cats, where the LD group had a lower impact on SAP and RR than the HD group.

Instillation of 5% Povidone-Iodine Ophthalmic Drops Decreases the Respiratory Rate in Children Undergoing Strabismus Surgery: A Randomized Controlled Trial.

PURPOSE: To investigate the effects of topical application of ophthalmic 5% povidone-iodine eye drops, which has been reported to cause apnea in spontaneously breathing children during general anesthesia. METHODS: The authors conducted a randomized, controlled, single-blinded study comparing the effect of balanced salt solution eye drops and povidone-iodine eye drops on respiration in spontaneously breathing children during general anesthesia with sevoflurane via a laryngeal mask airway. Fifty patients received balanced salt solution eye drops and 50 patients received 5% povidone-iodine eye drops. RESULTS: None of the control patients had a significant change in respiration. Thirty of the 50 (60%) povidone-iodine patients had a slowing of respiration within the first 6 breaths after eye drop instillation (P < .001). The median time of respiratory pause in those 30 patients was 18.5 seconds (range: 4.36 to 96.2 seconds). Among the povidone-iodine patients, children with a history of a prior tonsillectomy and adenoidectomy and/or bilateral myringotomy had a 7.2 times greater chance of experiencing a change in respiration after instillation of the povidone-iodine eye drops. CONCLUSIONS: Topical application of 5% povidone-iodine eye drops causes a slowing and pause in spontaneous ventilation in a majority of children prior to strabismus surgery. This may represent activation of the diving reflex. [J Pediatr Ophthalmol Strabismus. 2019;56(6):378-382.].

Influence of lavender oil inhalation on vital signs and anxiety: A randomized clinical trial.

OBJECTIVE: To investigate the effectiveness of lavender oil (Lavandula angustifolia Mill) inhalation on anxiety, mood, and vital signs (blood pressure, respiratory rate, heart rate, and saturation) of patients undergoing oral surgery. Vital signs were considered as primary outcome measures. Paired anxiety tests were used as secondary outcome measures. METHODS: Patients who had dental anxiety according to the Dental Anxiety Questionnaire (DAQ) were enrolled in the study. One hundred twenty-six patients who were undergoing wisdom tooth removal under local anaesthesia were randomly assigned to the lavender oil and control groups. Paired anxiety tests (Modified Dental Anxiety Scale and State-Trait Anxiety Inventory-State Scale were performed. Vital signs were noted pre-, intra-, and post-operatively. Visual analogue scale (VAS) results were assessed. The patients' degree of satisfaction was noted. RESULTS: Pre-operative anxiety levels were similar in both groups. Significant changes in blood pressure were observed in the lavender oil group post-operatively (p < .05). Most (79.4%) of the patients in the lavender oil group enjoyed the scent, 89.68% were satisfied with their experience, and 97.62% of the patients stated that they would prefer the same protocol when needed. CONCLUSION: Inhalation of lavender oil, which is one of the most powerful anxiolytic essential oils, reduces peri-operative anxiety and can be prospectively considered in future studies for its potential sedative characteristics in patients undergoing surgical procedures under local anaesthesia. TRIAL REGISTRATION NUMBER: NCT03722771 (Influence of Lavender Oil on Vital Signs in Oral Surgery Patients) https://clinicaltrials.gov/ct2/show/NCT03722771.