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.

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.

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia.

The lateral parabrachial nucleus (PBL) is implicated in the regulation of respiratory activity. Sodium leak channel (NALCN) mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and humans. Here, we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general anesthesia. Our results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency (RF) in mice; whereas chemogenetic inhibition suppressed RF. NALCN knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane anesthesia. NALCN knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or morphine. Under sevoflurane anesthesia, painful stimuli rapidly increased the RF, which was not affected by NALCN knockdown in PBL glutamatergic neurons. This study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.

Respiratory Responses to Single Oral Administration of Taurine in Sprague-Dawley Rats.

Taurine is a nonessential amino acid that has been increasingly consumed due to its various beneficial biological effects. Excessive taurine intake has been linked to the positive regulation of inflammatory responses and endoplasmic reticulum stress through the modulation of intracellular calcium levels. However, research on the potential adverse effects of taurine consumption on the respiratory system is limited. To address this, we investigated the respiratory responses of 6-week-old male Sprague-Dawley rats to taurine administered orally at 0, 100, 200, and 400 mg/kg. Respiratory rate, tidal volume, and minute volume were monitored in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Harmonized Tripartite Guideline S7A for Safety Pharmacology Studies for Human Pharmaceuticals. We found that taurine administration did not significantly alter respiratory rate or tidal volume; however, a significant increase in minute volume was observed 6 h after administration of 200 mg/kg taurine.

A Comparison of Three Anesthetic Drug Combinations for Use in Inducing Surgical Anesthesia in Female Guinea Pigs (Cavia porcellus).

Guinea pigs are often used in translational research, but providing them with safe and effective anesthesia is a challenge. Common methods like inhalant anesthesia and injectable ketamine/xylazine induce surgical anesthesia but can negatively affect cardiovascular, respiratory, and thermoregulatory systems and complicate the interpretation of research outcomes. Several alternative anesthetic regimens have been investigated, but none have consistently achieved a surgical plane of anesthesia. Therefore, identifying an anesthetic regimen that achieves a stable state of the surgical plane of anesthesia while preserving cardiorespiratory function would be a valuable contribution. To address this issue, we compared the efficacy of 3 anesthetic combinations in female Dunkin-Hartley guinea pigs: 1) alfaxalone, dexmedetomidine, and fentanyl (ADF); 2) alfaxalone, midazolam, and fentanyl (AMF); and 3) alfaxalone, midazolam, fentanyl, and isoflurane (AMFIso). We monitored anesthetic depth, heart rate, oxygenation, respiratory rate, respiratory effort, blood pressure, and body temperature every 15 min from injection to recovery. We also recorded the time to loss of righting reflex, duration of anesthesia, and time to achieve a surgical plane. The results showed no statistically significant differences in induction and recovery times among the groups. In the AMFIso group, 100% of the animals achieved a surgical plane of anesthesia, whereas only 10% of the animals in the AMF group reached that level. None of the animals in ADF group reached a surgical plane of anesthesia. Respiratory rate was significantly lower in the AMFIso as compared with the ADF group (P < 0.001) but was not different between the AMF and ADF groups. Temperature was significantly lower in the AMFIso group as compared with both the ADF and AMF groups (P < 0.001). In conclusion, both combinations of solely injectable anesthetics assessed in this study can be used for short, nonpainful procedures without significant cardiorespiratory depression. However, for mildly to moderately painful surgical procedures, the addition of an inhalant anesthetic like isoflurane is necessary for female guinea pigs.

Ampakine CX614 increases respiratory rate in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra compacta (SNpc). In a mouse model of PD induced by the injection of 6-hydroxydopamine (6-OHDA) into the caudate putamen (CPu) dyspnea events are very common. Neuroanatomical and functional studies show that the number of glutamatergic neurons in the pre-Bötzinger Complex (preBötC) are reduced. We hypothesize that the neuronal loss, and consequently loss of glutamatergic connections in the respiratory network previously investigated, are responsible for the breathing impairment in PD. Here, we tested whether ampakines (CX614), a subgroup of AMPA receptor positive allosteric modulators, could stimulate the respiratory activity in PD-induced animals. CX614 (50 µM) injected intraperitoneally or directly into the preBötC region reduced the irregularity pattern and increased the respiratory rate by 37% or 82%, respectively, in PD-induced animals. CX614 also increased the respiratory frequency in healthy animals. These data suggest that ampakine CX614 could become a tool to restore breathing in PD.

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.

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.

Pharmacological antagonism of EP2 receptor does not modify basal cardiovascular and respiratory function, blood cell counts, and bone morphology in animal models.

The EP2 receptor has emerged as a therapeutic target with exacerbating role in disease pathology for a variety of peripheral and central nervous system disorders. We and others have recently demonstrated beneficial effects of EP2 antagonists in preclinical models of neuroinflammation and peripheral inflammation. However, it was earlier reported that mice with global EP2 knockout (KO) display adverse phenotypes on fertility and blood pressure. Other studies indicated that EP2 activation with an agonist has a beneficial effect of healing fractured bone in animal models. These results impeded the development of EP2 antagonists, and EP2 antagonism as therapeutic strategy. To determine whether treatment with EP2 antagonist mimics the adverse phenotypes of the EP2 global KO mouse, we tested two EP2 antagonists TG11-77. HCl and TG6-10-1 in mice and rats while they are on normal or high-salt diet, and by two different administration protocols (acute and chronic). There were no adverse effects of the antagonists on systolic and diastolic blood pressure, heart rate, respiratory function in mice and rats regardless of rodents being on a regular or high salt diet. Furthermore, chronic exposure to TG11-77. HCl produced no adverse effects on blood cell counts, bone-volume and bone-mineral density in mice. Our findings argue against adverse effects on cardiovascular and respiratory systems, blood counts and bone structure in healthy rodents from the use of small molecule reversible antagonists for EP2, in contrast to the genetic ablation model. This study paves the way for advancing therapeutic applications of EP2 antagonists against diseases involving EP2 dysfunction.

Noninvasive ventilation and high-flow nasal cannula in patients with acute hypoxemic respiratory failure by covid-19: A retrospective study of the feasibility, safety and outcomes.

BACKGROUND: Noninvasive ventilation (NIV) and High-flow nasal cannula (HFNC) are the main forms of treatment for acute respiratory failure. This study aimed to evaluate the effect, safety, and applicability of the NIV and HFNC in patients with acute hypoxemic respiratory failure (AHRF) caused by COVID-19. METHODS: In this retrospective study, we monitored the effect of NIV and HFNC on the SpO2 and respiratory rate before, during, and after treatment, length of stay, rates of endotracheal intubation, and mortality in patients with AHRF caused by COVID-19. Additionally, data regarding RT-PCR from physiotherapists who were directly involved in assisting COVID-19 patients and non-COVID-19. RESULTS: 62.2 % of patients were treated with HFNC. ROX index increased during and after NIV and HFNC treatment (P < 0.05). SpO2 increased during NIV treatment (P < 0.05), but was not maintained after treatment (P = 0.17). In addition, there was no difference in the respiratory rate during or after the NIV (P = 0.95) or HFNC (P = 0.60) treatment. The mortality rate was 35.7 % for NIV vs 21.4 % for HFNC (P = 0.45), while the total endotracheal intubation rate was 57.1 % for NIV vs 69.6 % for HFNC (P = 0.49). Two adverse events occurred during treatment with NIV and eight occurred during treatment with HFNC. There was no difference in the physiotherapists who tested positive for SARS-COV-2 directly involved in assisting COVID-19 patients and non-COVID-19 ones (P = 0.81). CONCLUSION: The application of NIV and HFNC in the critical care unit is feasible and associated with favorable outcomes. In addition, there was no increase in the infection of physiotherapists with SARS-CoV-2.

Buprenorphine differentially alters breathing among four congenic mouse lines as a function of dose, sex, and leptin status.

The opioid buprenorphine alters breathing and the cytokine leptin stimulates breathing. Obesity increases the risk for respiratory disorders and can lead to leptin resistance. This study tested the hypothesis that buprenorphine causes dose-dependent changes in breathing that vary as a function of obesity, leptin status, and sex. Breathing measures were acquired from four congenic mouse lines: female and male wild type C57BL/6J (B6) mice, obese db/db and ob/ob mice with leptin dysfunction, and male B6 mice with diet-induced obesity. Mice were injected intraperitoneally with saline (control) and five doses of buprenorphine (0.1, 0.3, 1.0, 3.0, 10 mg/kg). Buprenorphine caused dose-dependent decreases in respiratory frequency while increasing tidal volume, minute ventilation, and respiratory duty cycle. The effects of buprenorphine varied significantly with leptin status and sex. Buprenorphine decreased minute ventilation variability in all mice. The present findings highlight leptin status as an important modulator of respiration and encourage future studies aiming to elucidate the mechanisms through which leptin status alters breathing.

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.

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.

Paternal preconception exposure to chronic morphine alters respiratory pattern in response to morphine in male offspring.

The clinical use of opioids is restricted by its deleterious impacts on respiratory system. Gaining a better understanding of an individual's susceptibility to adverse opioid effects is important to recognize patients at risk. Ancestral drug addiction has been shown to be associated with alterations in drug responsiveness in the progenies. In the current study, we sought to evaluate the effects of preconception paternal morphine consumption on respiratory parameters in response to acute morphine in male offspring during adulthood, using plethysmography technique. Male Wistar rats administered 10 days of increasing doses of morphine in the period of adolescence. Thereafter, following a 30-day abstinence time, adult males copulated with naïve females. The adult male offspring were examined for breathing response to morphine. Our results indicated that sires who introduce chronic morphine during adolescence leads to increase irregularity of respiratory pattern and asynchronization between inter-breath interval (IBI) and respiratory volume (RV) time series in male offspring. These findings provide evidence that chronic morphine use by parents even before pregnancy can affect respiratory pattern and response to morphine in the offspring.

Differential effects of four intramuscular sedatives on cardiorespiratory stability in juvenile guinea pigs (Cavia porcellus).

BACKGROUND: Non-invasive physiological monitoring can induce stress in laboratory animals. Sedation reduces the level of restraint required, thereby improving the validity of physiological signals measured. However, sedatives may alter physiological equilibrium introducing unintended bias and/or, masking the experimental outcomes of interest. We aimed to investigate the cardiorespiratory effects of four short-acting sedatives in juvenile guinea pigs. METHOD: 12 healthy, 38 (26-46) day-old Dunkin Hartley guinea pigs were included in this blinded, randomised, crossover design study. Animals were sedated by intramuscular injection using pre-established minimum effective doses of either alfaxalone (5 mg/kg), diazepam (5 mg/kg), ketamine (30 mg/kg), or midazolam (2 mg/kg) administered in random order with a minimum washout period of 48 hours between agents. Sedative depth, a composite score comprised of five assessment criteria, was observed every 5-min from dosing until arousal. Physiological monitoring of cardiorespiratory status included measures of heart rate, blood pressure, respiratory rate, and peripheral microvascular perfusion. RESULTS: Ketamine and alfaxalone were most effective in inducing stable sedation suitable for physiological monitoring, and diazepam less-so. Midazolam was unsuitable due to excessive hypersensitivity. All sedatives significantly increased heart rate above non-sedated control rates (P<0.0001), without altering blood pressure or microvascular perfusion. Alfaxalone and ketamine reduced respiratory rate relative to their control condition (P<0.0001, P = 0.05, respectively), but within normative ranges. CONCLUSION: Ketamine and alfaxalone are the most effective sedatives for inducing short duration, stable sedation with minimal cardiorespiratory depression in guinea pigs, while diazepam is less-so. However, alfaxalone is the most appropriate sedative for longitudinal studies requiring multiple physiological timepoints.

Long-term stability of physiological signals within fluctuations of brain state under urethane anesthesia.

Urethane, an acute laboratory anesthetic, produces distinct neurophysiological and physiological effects creating an effective model of the dynamics of natural sleep. As a model of both sleep-like neurophysiological activity and the downstream peripheral function urethane is used to model a variety of physiological and pathophysiological processes. As urethane is typically administered as a single-bolus dose, it is unclear the stability of peripheral physiological functions both within and between brain-states under urethane anesthesia. In this present study, we recorded respiration rate and heart rate concurrently with local field potentials from the neocortex and hippocampus to determine the stability of peripheral physiological functions within and between brain-states under urethane anesthesia. Our data shows electroencephalographic characteristics and breathing rate are remarkable stable over long-term recordings within minor reductions in heart rate on the same time scale. Our findings indicate that the use of urethane to model peripheral physiological functions associated with changing brain states are stable during long duration experiments.

Effects of Controlled Generator Fume Emissions on the Levels of Troponin I, C-Reactive Protein and Oxidative Stress Markers in Dogs: Exploring Air Pollution-Induced Cardiovascular Disease in a Low-Resource Country.

Exhaust fumes from petrol/diesel-powered electric generators contribute significantly to air pollution in many developing countries, constituting health hazards to both humans and animals. This study evaluated the serum concentrations of Troponin I (TnI), C-reactive protein (CRP) and serum levels/activities of oxidative stress markers: catalase (CAT), reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD) in dogs experimentally exposed to graded levels of petrol generator exhaust fume (PGEF). Sixteen (16) healthy and adult male Basenji dogs were randomly assigned into four groups (A-D). Group A was the unexposed control while groups B, C and D were exposed to PGEF for 1, 2 and 3 h per day, respectively, for 90 days. Repeated analysis were performed at the baseline, and every thirty days, for a total of 90 days. There was a significant interaction (p < 0.05) between the effects of PGEF exposure level (in h/day) and duration of exposure (in months) on all the tested serum parameters. There was a significant main effect (p < 0.05) for PGEF exposure level on the serum parameters. As the level of PGEF exposure was increased, the serum concentrations of TnI, CRP, CAT, MDA and NO increased, GSH decreased, whereas SOD activity increased by day 30 but declined at the end. Moreover, there was a significant simple main effect (p < 0.05) for duration of PGEF exposure. All the parameters increased as the duration of PGEF exposure was increased to 90 days except GSH concentration which decreased, whereas SOD activity increased initially but declined at the end of the study. Thus, there was increased serum concentrations of TnI, CRP and increased oxidative stress in the PGEF-exposed dogs. These findings are instructive and could be grounds for further studies on air pollutants-induced cardiovascular disease given the widespread use of electricity generators in many low-resource countries.

The involvement of the central cholinergic system in the hyperventilation effect of centrally injected nesfatin-1 in rats.

We recently demonstrated that peripheral and central administration of nesfatin-1 in fasting and satiety states generate hyperventilation activity by increasing tidal volume (TV), respiratory rate (RR), and respiratory minute ventilation (RVM). The present study aimed to investigate the mediation of central cholinergic receptors effective in respiratory control in the hyperventilation activity of nesfatin-1. Besides this, we intended to determine possible changes in blood gases due to hyperventilation activity caused by nesfatin-1 and investigate the mediation of central cholinergic receptors in these changes. Intracerebroventricular (ICV) administration of nesfatin-1 revealed a hyperventilation response with an increase in TV, RR, RMV, and pO2 and a decrease in pCO2 in saturated Sprague Dawley rats. ICV pretreatment with the muscarinic receptor antagonist atropine partially blocked the RR, RMV, pO2, and pCO2 responses produced by nesfatin-1 while completely blocking the TV response. However, central pretreatment with nicotinic receptor antagonist mecamylamine blocked the respiratory and blood gas responses induced by nesfatin-1. The study's conclusion demonstrated that nesfatin-1 had active hyperventilation effects resulting in an increase in pO2 and a decrease in pCO2. The critical finding of the study was that activation of central cholinergic receptors was involved in nesfatin-1-evoked hyperventilation and blood gas responses.

Effects of fadolmidine, an α2 -adrenoceptor agonist, as an adjuvant to spinal bupivacaine on antinociception and motor function in rats and dogs.

α2 -Adrenoceptor agonists such as clonidine and dexmedetomidine are used as adjuvants to local anesthetics in regional anesthesia. Fadolmidine is an α2 -adrenoceptor agonist developed especially as a spinal analgesic. The current studies investigate the effects of intrathecally administered fadolmidine with a local anesthetic, bupivacaine, on antinociception and motor block in conscious rats and dogs. The antinociceptive effects of intrathecal fadolmidine and bupivacaine alone or in combination were tested in the rat tail-flick and the dog's skin twitch models. The durations of motor block in rats and in dogs were also assessed. In addition, the effects on sedation, mean arterial blood pressure, heart rate, respiratory rate and body temperature were evaluated in telemetrized dogs. Concentrations of fadolmidine in plasma and spinal cord were determined after intrathecal and intravenous administration in rats. Co-administration of intrathecal fadolmidine with bupivacaine increased the magnitude and duration of the antinociceptive effects and prolonged motor block without hypotension. The interaction of the antinociceptive effect was synergistic in its nature in rats. Concentration of fadolmidine in plasma was very low after intrathecal dosing. Taken together, these studies show that fadolmidine as an adjuvant to intrathecal bupivacaine provides enhanced sensory-motor block and enables a reduction of the doses of both drugs. The results indicate that co-administration of fadolmidine with intrathecal bupivacaine was able to achieve an enhanced antinociceptive effect without hypotension and could thus represent a suitable combination for spinal anesthesia.