Repeated Administration of the Cannabinoid WIN Alters the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine.

The impacts of morphine and dexmedetomidine on the MAC of isoflurane were studied in rats constantly medicated with the cannabinoid WIN 55,212-2. METHODS: Prior to the administration of morphine, the MAC was measured in both untreated rats (MAC (ISO)) and those treated with a cannabinoid (MAC (ISO + CANN)). The effects of morphine (MAC (ISO + MOR)) and dexmedetomidine (MAC (ISO + DEX)) on untreated rats and rats treated for 21 days with the cannabinoids (MAC (ISO + CANN + MOR)) and (MAC (ISO + CANN + DEX) were also studied. RESULTS: MAC (ISO) was 1.32 ± 0.06, and MAC (ISO + CANN) was 1.69 ± 0.09. MAC (ISO + MOR) was 0.97 ± 0.02 (26% less than MAC (ISO)). MAC (ISO + CANN + MOR) was 1.55 ± 0.08 (8% less than MAC (ISO + CANN)), MAC (ISO + DEX) was 0.68 ± 0.10 (48% less than MAC (ISO)), and MAC (ISO + CANN + DEX) was 0.67 ± 0.08 (60% less than MAC (ISO + CANN)). CONCLUSIONS: Medication with a cannabinoid for 21 days augmented the MAC of isoflurane. The sparing effect of morphine on isoflurane is lower in rats constantly medicated with a cannabinoid. The sparing effect of dexmedetomidine on the minimum alveolar concentration of isoflurane is greater in rats repeatedly medicated with a cannabinoid.

Effects of Microencapsulated Essential Oils on Equine Health: Nutrition, Metabolism and Methane Emission.

This review examines the available data regarding the positive effects of microencapsulated essential oils (EOs) on the nutrition, metabolism, and possibly the methane emission of horses. A literature review was conducted on the effect of microencapsulated (EOs) on the health of horses. The information comprises articles published in recent years in indexed journals. The results indicate that mixtures of microencapsulated EOs may be beneficial to equine health due to their antimicrobial and antioxidant activity, as well as their effects on enteric methane production, nutrient absorption, and immune system enhancement. Moreover, encapsulation stabilizes substances such as EOs in small doses, primarily by combining them with other ingredients.

Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review.

The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19. The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms. A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a. The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood-nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.

Minimum Alveolar Concentration of Isoflurane in Rats Chronically Treated with the Synthetic Cannabinoid WIN 55,212-2.

The minimum alveolar concentration MAC of isoflurane was measured in rats chronically treated with WIN 55,212-2. METHODS: The MAC of isoflurane was determined in 24 male rats from expiratory samples at time of tail clamping under the following conditions: without treatment MAC(ISO), in rats treated for 21 days with WIN 55,212-2 MAC(ISO + WIN55), and in rats 8 days after stopping treatment with WIN 55,212-2 (MACISO + WIN55 + 8D). RESULTS: The MAC(ISO) was 1.32 ± 0.06. In the MAC(ISO + WIN55) group, the MAC increased to 1.69 ± 0.09 (28%, p-value ≤ (0.0001). Eight days after stopping treatment with WIN55, the MAC did not decrease significantly, 1.67 ± 0.07 (26%, p-value ≤ 0.0001). CONCLUSIONS: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. This effect does not disappear 8 days after discontinuation of treatment with the synthetic cannabinoid.

Lower ΔFosB expression in the dopaminergic system after stevia consumption in rats housed under environmental enrichment conditions.

Environmental enrichment (EE) has been proven to reduce drug seeking and the development of addiction-related behaviors in rodent models, but the effects of EE on natural reward acquisition in the form of sweet beverages are poorly understood. Accumulating evidence shows that the intake of sugar, the main ingredient of sweet beverages, alters the dopaminergic system, leading to addiction-related physiological and molecular changes. Sugar in sweet beverages has been replaced with natural sweeteners, such as stevia extract, which has greater sweetener potential but no energy content. Our research group found that sucralose consumption increased the expression of ΔFosB in reward-related nuclei, suggesting activation of the dopaminergic system. The present study assessed the effects of EE on stevia consumption and the expression of ΔFosB in the nucleus accumbens, caudate putamen, and prefrontal cortex. Sixteen male Wistar rats, 21 days old, were randomly assigned to an EE group (n = 8) or standard environment (SE) group (n = 8) and reared for 30 days. On postnatal day 52 (PND52), the brains of four animals in each housing condition were extracted to determine basal ΔFosB levels. Stevia consumption with intermittent access and ΔFosB immunoreactivity were measured for 21 days in the remainder of the rats. Compared with SE animals, EE animals exhibited a reduction of stevia consumption and alterations of ΔFosB immunoreactivity in the reward system. These results indicate that EE reduces stevia consumption and the stevia-induced ΔFosB expression, suggesting addiction-related changes in dopaminergic nuclei, which may be interpreted as a neuroprotective effect.

Clinical Use of The Parasympathetic Tone Activity Index As a Measurement of Postoperative Analgaesia in Dogs Undergoing Ovariohysterectomy.

INTRODUCTION: While the current tools to assess canine postoperative pain using physiological and behavioural parameters are reliable, an objective method such as the parasympathetic tone activity (PTA) index could improve postoperative care. The aim of the study was to determine the utility of the PTA index in assessing postoperative analgaesia. MATERIAL AND METHODS: Thirty healthy bitches of different breeds were randomly allocated into three groups for analgaesic treatment: the paracetamol group (GPARAC, n = 10) received 15 mg/kg b.w., the carprofen group (GCARP, n = 10) 4 mg/kg b.w., and the meloxicam group (GMELOX, n = 10) 0.2 mg/kg b.w. for 48 h after surgery. GPARAC was medicated orally every 8 h, while GCARP and GMELOX were medicated intravenously every 24 h. The PTA index was used to measure the analgaesia-nociception balance 1 h before surgery (baseline), and at 1, 2, 4, 6, 8, 12, 16, 20, 24, 36, and 48 h after, at which times evaluation on the University of Melbourne Pain Scale (UMPS) was made. RESULTS: The baseline PTA index was 65 ± 8 for GPARAC, 65 ± 7 for GCARP, and 62 ± 5 for GMELOX. Postoperatively, it was 65 ± 9 for GPARAC, 63 ± 8 for GCARP, and 65 ± 8 for GMELOX. No statistically significant difference existed between baseline values or between values directly after treatments (P = 0.99 and P = 0.97, respectively). The PTA index showed a sensitivity of 40%, specificity of 98.46% and a negative predictive value of 99.07%. CONCLUSION: Our findings suggest that the PTA index measures comfort and postoperative analgaesia objectively, since it showed a clinical relationship with the UMPS.

Clinical evaluation of postoperative analgesia, cardiorespiratory parameters and changes in liver and renal function tests of paracetamol compared to meloxicam and carprofen in dogs undergoing ovariohysterectomy.

BACKGROUND: In veterinary medicine, the administration of nonsteroidal anti-inflammatory analgesics (NSAIDs) for the control of postsurgical pain in dogs and cats is common given the anti-inflammatory, analgesic, and antipyretic effects of these drugs. This study compared the serum biochemical changes and postoperative analgesic effects of paracetamol, meloxicam, and carprofen in bitches submitted to an ovariohysterectomy using the Dynamic Interactive Visual Analog Scale (DIVAS) and Pain Scale of the University of Melbourne (UMPS) scoring systems. METHODS: Thirty bitches of different breeds underwent elective ovariohysterectomies and were randomly assigned to one of three treatment groups: a paracetamol group [15 mg kg-1 intravenous (IV)], a carprofen group (4 mg kg-1 IV), and a meloxicam group (0.2 mg kg-1 IV). All treatments were administered 30 minutes prior to surgery. Paracetamol was administered every 8 hours postoperatively for 48 hours total, while carprofen and meloxicam were intravenously administered every 24 hours. An evaluation of post-surgical pain was done with the DIVAS and the UMPS. The first post-surgical pain measurement was performed 1 hour after surgery and then 2, 4, 6, 8, 12, 16, 20, 24, 36, and 48 hours after surgery. RESULTS: All groups exhibited a gradual reduction in pain throughout the postoperative period in both scales; however, neither scale significantly differed between the three treatment groups (P > 0.05) during the 48 postoperative hours. CONCLUSIONS: Paracetamol was as effective as meloxicam and carprofen for post-surgical analgesia in bitches subjected to elective ovariohysterectomy. The present study demonstrates that paracetamol may be considered a tool for the effective treatment of acute perioperative pain in dogs. Furthermore, this drug led to no adverse reactions or changes in the parameters assessed in the present study, indicating its safety.

Cannabinoids CB2 Receptors, One New Promising Drug Target for Chronic and Degenerative Pain Conditions in Equine Veterinary Patients.

Osteoarticular equine disease is a common cause of malady; in general, its therapy is supported on steroids and nonsteroidal anti-inflammatories. Nevertheless, many side effects may develop when these drugs are administered. Nowadays, the use of new alternatives for this pathology attention is demanded; in that sense, cannabinoid CB2 agonists may represent a novel alternative. Cannabinoid belongs to a group of molecules known by their psychoactive properties; they are synthetized by the Cannabis sativa plant, better known as marijuana. The aim of this study was to contribute to understand the pharmacology of cannabinoid CB2 receptors and its potential utilization on equine veterinary patients with a chronic degenerative painful condition. In animals, two main receptors for cannabinoids are recognized, the cannabinoid receptor type 1 and the cannabinoid receptor type 2. Once they are activated, both receptors exert a wide range of physiological responses, as nociception modulation. Recently, it has been proposed the use of synthetic cannabinoid type 2 receptor agonists; those receptors looks to confer antinociceptive properties but without the undesired psychoactive side effects; for that reason, veterinary patients, whit chronical degenerative diseases as osteoarthritis may alleviate one of the most common symptom, the pain, which in some cases for several reasons, as patient individualities, or side effects produced for more conventional treatments cannot be attended in the best way.

Anandamide and sucralose change ΔFosB expression in the reward system.

Food reward has been studied with highly palatable stimuli that come from natural additives such as sucrose. The most common food additive is sucralose, a noncaloric sweetener present in many food products of daily intake. The role of anandamide [N-arachidonylethanolamide (AEA)], an endogenous cannabinoid, has been widely studied in food behavior. Studies have shown that cannabinoids, such as AEA, 2-Arachidonilglycerol, and Tetrahydrocannabinol, can provoke hyperphagia, because they enhance the preference and intake of sweet and high-fat food. Taste perception is mediated by receptors taste type 1 receptor 3 (T1R3); therefore, there could be a synergistic effect between receptors CB1 and T1R3. This could explain why cannabinoids could change sweet taste perception and therefore the activity of neural nuclei involved in taste and reward. In this study, we evaluated the activity of dopaminergic nuclei implicated in food reward after the chronic administration of AEA (0.5 mg/kg bw) and sucralose intake (0.02%). We analyzed the expression of ΔFosB by immunohistochemistry. Our results show that the chronic administration of AEA and sucralose intake induces an overexpression of ΔFosB in the infralimbic cortex (Cx), nucleus accumbens (NAc) core, shell, and central nucleus of amygdala (Amy). These results suggest that the possible interaction between receptors CB1 and T1R3 has consequences not only in taste perception but also that AEA intervenes in the activity of dopaminergic nuclei such as the NAc, and that the chronic administration AEA and sucralose intake induce long-term changes in the reward system.

Pharmacological Regulation in the USA and Pharmacokinetics Parameters of Firocoxib, a Highly Selective Cox-2, by Pain Management in Horses.

The objective of the study was to conduct a review of the pharmacological regulation and pharmacokinetic parameters of firocoxib when administered orally or intravenously in horses. A search for literature was done in SCOPUS and PubMed for studies that had to evaluate the pharmacological regulation as well as the pharmacokinetic parameters of firocoxib when administered in horses. The nonsteroidal anti-inflammatory drugs have analgesic, anti-inflammatory, antipyretics, and antiendotoxic effects. The newly developed is selective to COX2 characterized by less adverse effects in veterinary patients when administered at the recommended doses and do not exceed the established prescribed time. Firocoxib is authorized by the Food and Drug Administration for the treatment of pain in horses, whereas for humans, there is still no approval. Controversy has arisen because the administration of the same pharmaceutical presentation in horses and dogs has pharmacokinetic differences between animal species. However, special attention must be paid to pharmacokinetic differences between species like in horses and dogs. In the case of the horse, the dosage is 0.1 mg/kg in single dose or up to 14 days in oral paste formulation and can keep maintained on the same concentration for a period of 7-14 days in oral tablet formulation. Thorough knowledge of pharmacological regulations and pharmacokinetic parameters, it allows the posology and effective application of firocoxib in pathologies associated with chronic pain, avoiding the indiscriminate use by owners and in some cases veterinarians, thus reducing the negative impacts on horse's health.

c-Fos immunoreactivity in the hypothalamus and reward system of young rats after social novelty exposure.

Socialization is an adaptive behavior during the early stages of life because it helps young animals become independent and determines healthy adult social behavior. Therefore, it is probable that the brain areas involved in the processing of social stimuli are more sensitive to social novelty during early life stages. To test this hypothesis, four groups of young male rats were exposed to different socioenvironmental stimuli; nonsocial physical novelty, social familiarity, social novelty, and a control group which received no stimulation. After stimuli exposure, brains were fixed and cut in coronal sections for c-Fos immunohistochemistry. The number of c-Fos-immunoreactive (c-Fos-ir) neurons in the paraventricular nucleus and supraoptic nucleus, the main producers of oxytocin and vasopressin, was compared, as well as in the nucleus accumbens and ventral pallidum, the main areas involved in reinforced behavior. A significantly higher number of c-Fos-ir neurons were found in animals exposed to social novelty in all areas, except in the supraoptic nucleus. In particular, the increase in c-Fos-ir in the paraventricular nucleus seems to be selective in response to social novelty, while the increase of c-Fos-ir in the nucleus accumbens and ventral pallidum suggests that social novelty during youth is a highly rewarding stimulus compared with social familiarity and nonsocial physical novelty.

Effects of Sodium Selenite, L-Selenomethionine, and Selenium Nanoparticles During Late Pregnancy on Selenium, Zinc, Copper, and Iron Concentrations in Khalkhali Goats and Their Kids.

The objective of this study was to evaluate the effect of organic, inorganic, and selenium nanoparticle supplements at the final stage of pregnancy on selenium, zinc, copper, and iron concentrations of goats and placental, colostrum, and milk transfer of these trace minerals from goats to their kids. Forty pregnant Khalkhali goats (30 ± 5 kg) were randomly allocated to four treatments including (1) no supplement (control), 0.6 mg Se head-1 day-1 of selenomethionine (SM), 0.6 mg Se head-1 day-1 of selenium nanoparticles (SN), and 0.6 mg Se head-1 day-1 of sodium selenite (SS), from 4 weeks before the expected day of delivery to delivery day. Blood samples were taken from the goats 4 weeks before the expected day of delivery and on the kidding day. Colostrum samples were collected from the goats immediately after kidding. Instantly after delivery, newborn kids were taken apart from their dams and their blood samples were collected from the jugular vein, before they drank their first colostrums and at 7, 14, 21, and 28 after birthday. The results demonstrated that the whole blood and serum Se concentration was greater in Se-supplemented goats compared with the control (P < 0.05). The total Se content of the whole blood and serum was higher in SN than in SM (P < 0.05) and SS goats (P < 0.05). At birth, the whole blood and serum concentration of Se was decreased (P < 0.05) in kids of SN-treated goats contrasted with the control ones (P < 0.05). The copper content of goats and their kids in treated goats was greater compared with control goats except for SN treated, which was decreased (P < 0.05). It was totally vice versa with Zn content trend in the whole blood, serum, and colostrum (P < 0.05), which was also concomitant with an increase in Fe content of kids of supplemented goats at birth and first week of life (P < 0.05). These results seem to indicate a higher efficacy of placental and colostral transfer of Se into kids of SM-treated goats when contrasted with either receiving comparable doses of SN or SS. It could be concluded that Se supplementation can affect and correlate with Cu, Zn, and Fe levels, and this effect depends a lot on the chemical or physical variety of Se supplementation.

Outbreak of Zika virus pathogenesis and quest of its vaccine development: Where do we stand now?

Zika virus (ZIKV) infection is a life-threatening tropical infection, mainly caused by mosquito bite. After a very long period of quietness, ZIKV infections have become a problematic issue again. Previously, the virus was limited to Africa and Asia only but later it emerged in Brazil, South America, and other parts of the world in 2015. In 2016, there are emerging new cases of sexually transmitted ZIKV infection as well. At present, there is no proper treatment and available pronounced vaccines for the treatment of ZIKV infection. The prime focal point of this review is not only to provide imperative epidemiological information on ZIKV infection in brief but also the current situation of vaccines testing on animal model as well as in clinical trial phases. Currently there is no human vaccine for this pestiferous viral infection. Therefore, prevention, proper management, and up-to-date recommendation are crucial to mitigate the possible risk of vector and non-vector transmission of ZIKV.

Antimicrobial and bactericidal impacts of Bacillus amyloliquefaciens CECT 5940 on fecal shedding of pathogenic bacteria in dairy calves and adult dogs.

Two experiments were carried out to evaluate the bactericidal impacts of Bacillus amyloliquefaciens CECT 5940 on the shedding of faecal pathogenic bacteria in dairy calves (Experiment 1) and in adults dogs (experiment 2). In the calves experiment, a completely randomized design was used to investigate the faecal bacteria profile of Holstein dairy calves fed with either pasteurized waste milk (PWM; n = 9) or a formulated non-medicated milk replacer (NMR; n = 9) for 60 d. The NMR containing sodium-butyrate and the active probiotic B. amyloliquefaciens CECT 5940. In the dogs experiment, addition of same probiotic (i.e., B. amyloliquefaciens CECT 5940) was carried out in two stages. The first stage started from day 7-37, and the second from day 44-71. The assessment of faecal score measured on day 22, 37, 42, 57, 71 and 77 to determine the texture of the stools. Calves received PWM consumed (P < 0.05) more starter feed between day 16 and day 45. The calves fed NMR had more moisture faeces and less cough reflux than the PWM-calves. Feeding NMR to calves increased faecal Klebsiella oxytoca and Proteus vulgaris counts in comparison to PWM-calves. The administration of B. amyloliquefaciens CECT 5940 to the dog diet has no significant effect on the hardness of the stool. Meanwhile, the bacillus count increases while the coliforms count decreases upon B. amyloliquefaciens CECT 5940 administration. This reveals that B. amyloliquefaciens CECT 5940 survived the gastrointestinal passage and rapidly colonized the dog intestine, which could positively affect the metabolism and composition of the intestinal microflora. These results show that B. amyloliquefaciens are a promising probiotic with an antimicrobial and bactericidal activities against the intestinal pathogenic bacteria for dairy calves and adult dogs.

Cardiovascular effects of constant rate infusions of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized at equipotent doses of sevoflurane.

This study evaluated the cardiovascular effects of a constant rate infusion (CRI) of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized with sevoflurane at equipotent doses. Treatments consisted of T1-Lidocaine [loading dose 2 mg/kg body weight (BW), IV, and CRI of 100 µg/kg BW per min] at 1.4% end-tidal of sevoflurane (FESEV); T2-Dexmedetomidine (loading dose 2 µg/kg BW, IV, and CRI of 2 µg/kg BW per hour) and FESEV 1.1%; and T3-Lidocaine-Dexmedetomidine using the same doses of T1 and T2 and FESEV 0.8%. Constant rate infusion of lidocaine did not induce any cardiovascular changes; lidocaine and dexmedetomidine resulted in cardiovascular effects similar to dexmedetomidine alone. These effects were characterized by a significant (P < 0.001) decrease in heart rate, cardiac output, cardiac index, oxygen delivery, and pulmonary vascular resistance index, and a significant (P < 0.001) increase in mean and diastolic arterial pressure, systemic vascular resistance index, pulmonary arterial occlusion pressure and oxygen extraction ratio, compared with baseline values. In conclusion, a CRI of lidocaine combined with dexmedetomidine produces significant cardiovascular changes similar to those observed with dexmedetomidine alone.

Effets cardiovasculaires des infusions constante de taux de lidocaïne, lidocaïne et dexmédétomidine, et dexmédétomidine chez chiens anesthésier at équipotent doses de sevoflurane. L'objet de cette etude a été la evaluation des effets cardo-vasculaires de la perfusion à debit continue (CRI) de lidocaïne, lidocaïene et dexmédétomidine, et dexmédétomidine en chiens anesthésiés avec sévoflurane dans équipotentiel dose. Les traitemets consistèrent á T1-Lidocaïne [dose de charge de 2 mg/kg, IV, et perfusion à debit continue (CRI) de 100 µg/kg/min] en 1,4 % en fin d'expiration du sévoflurane (FESEV); T2-Déxmédetomidine (dose de charge de 2 µg/kg, IV, et perfusion à debit continue (CRI) de 2 µg/kg/h) et FESEV 1,1 % et T3-Lidocaïne-Dexmédétomidine en utilisant la même dose de T1 et T2 et FESEV 0,8 %. Perfusion à debit continue (CRI) de lidocaïne ne induit pas aucun échange cardio-vasculaire; lidocaïne et dexmédétomidine resulta dans effets cardio-vasculaires similaires a dexmédétomidine seule. Ces effets caracterices par significative décroissance (P < 0,001) en fréquence cardiaque, le débit cardiaque, index cardiaque, la libération de l'oxygène, pulmonaire indice de résistance vasculaire, et significative accroissement de la moyenne a la pression artériele diastolique (P < 0,001), indice de résistance vasculaire systémique, et l'extraction d'oxygène. En somme, la perfusion à debit continue (CRI) de lidocaïne produit significative échange cardio-vasculaire similaire à ceux observe en itilisant seulement dexmédétomidine.(Traduit par les auteurs).

Effect of Acetaminophen Alone and in Combination with Morphine and Tramadol on the Minimum Alveolar Concentration of Isoflurane in Rats.

BACKGROUND: It has been observed that acetaminophen potentiates the analgesic effect of morphine and tramadol in postoperative pain management. Its capacity as an analgesic drug or in combinations thereof to reduce the minimum alveolar concentration (MAC) of inhalational anesthetics represents an objective measure of this effect during general anesthesia. In this study, the effect of acetaminophen with and without morphine or tramadol was evaluated on the isoflurane MAC. METHODS: Forty-eight male Wistar rats were anesthetized with isoflurane in oxygen. MACISO was determined from alveolar gas samples at the time of tail clamping without the drug, after administering acetaminophen (300 mg/kg), morphine (3 mg/kg), tramadol (10 mg/kg), acetaminophen (300 mg/kg) + morphine (3 mg/kg), and acetaminophen (300 mg/kg) + tramadol (10 mg/kg). RESULTS: The control and acetaminophen groups did not present statistically significant differences (p = 0.98). The values determined for MACISO after treatment with acetaminophen + morphine, acetaminophen + tramadol, morphine, and tramadol were 0.98% ± 0.04%, 0.99% ± 0.009%, 0.97% ± 0.02%, and 0.99% ± 0.01%, respectively. CONCLUSIONS: The administration of acetaminophen did not reduce the MAC of isoflurane and did not potentiate the reduction in MACISO by morphine and tramadol in rats, and therefore does not present a sparing effect of morphine or tramadol in rats anesthetized with isoflurane.

Lidocaine, dexmedetomidine and their combination reduce isoflurane minimum alveolar concentration in dogs.

The effects of intravenous (i.v.) lidocaine, dexmedetomidine and their combination delivered as a bolus followed by a constant rate infusion (CRI) on the minimum alveolar concentration of isoflurane (MACISO) in dogs were evaluated. Seven healthy adult dogs were included. Anaesthesia was induced with propofol and maintained with isoflurane. For each dog, baseline MAC (MACISO/BASAL) was determined after a 90-minute equilibration period. Thereafter, each dog received one of the following treatments (loading dose, CRI): lidocaine 2 mg kg(-1), 100 µg kg(-1) minute(-1); dexmedetomidine 2 µg kg(-1), 2 µg kg(-1) hour(-1); or their combination. MAC was then determined again after 45- minutes of treatment by CRI. At the doses administered, lidocaine, dexmedetomidine and their combination significantly reduced MACISO by 27.3% (range: 12.5-39.2%), 43.4% (33.3-53.3%) and 60.9% (46.1-78.1%), respectively, when compared to MACISO/BASAL. The combination resulted in a greater MACISO reduction than the two drugs alone. Their use, at the doses studied, provides a clinically important reduction in the concentration of ISO during anaesthesia in dogs.

Effects of sildenafil on the fetal growth of guinea pigs and their ability to survive induced intrapartum asphyxia.

OBJECTIVE: Our goal was to determine whether sildenafil increased fetal weight and favored fetal tolerance to induced asphyxia at birth in guinea pigs. STUDY DESIGN: Twenty guinea pigs were randomly allocated to placebo (n = 10) or sildenafil 50 microg/kg (n = 5) or 500 microg/kg (n = 5), starting from day 35 of gestation to delivery. Fetuses were delivered by cesarean section. Fetal asphyxia was induced by clamping the umbilical cord at birth for 5 minutes. RESULTS: Sildenafil protected the pups against induced asphyxia at birth in a dose-dependent manner (eg, partial pressure (tension) of carbon dioxide levels were 75.9 +/- 19.3, 66.9 +/- 18.8, and 54.8 +/- 13.0 in the control and low- and high-dose sildenafil groups, respectively). The high-dose sildenafil group of piglets gained 1.5 times more body weight. CONCLUSION: In guinea pigs, low doses of sildenafil administered from day 35 to the end of gestation favored fetal tolerability to induced intrapartum asphyxia. High doses of sildenafil increased fetal weight.