Isoflurane preconditioning protects against renal ischemia/reperfusion injury in diabetes via activation of the Brg1/Nrf2/HO-1 signaling pathway.

PURPOSE: To examine whether isoflurane preconditioning (IsoP) has a protective effect against renal ischemia/reperfusion injury (I/RI) in diabetic conditions and to further clarify the underlying mechanisms. METHODS: Control and streptozotocin-induced diabetic rats were randomly assigned to five groups, as follows: normal sham, normal I/R, diabetic sham, diabetic I/R, and diabetic I/R + isoflurane. Renal I/RI was induced by clamping renal pedicle for 45 min followed by reperfusion for 24 h. IsoP was achieved by exposing the rats to 2% isoflurane for 30 min before vascular occlusion. Kidneys and blood were collected after reperfusion for further analysis. Renal histology, blood urea nitrogen, serum creatinine, oxidative stress, inflammatory cytokines, and renal cell apoptosis were assessed. Furthermore, the expression of brahma related gene 1 (Brg1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) were determined. RESULTS: Compared with control, diabetic rats undergoing I/R presented more severe renal injury, oxidative stress, inflammatory reaction, and apoptosis with the impairment of Brg1/Nrf2/HO-1 signaling. All these alterations were significantly attenuated by pretreatment with isoflurane. CONCLUSIONS: These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.

Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy.

Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n=28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) versus 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.

Minimum anesthetic concentration of isoflurane and sevoflurane and cardiorespiratory effects of varying inspired oxygen fractions in Magellanic penguins (Spheniscus magellanicus).

The aim of this study was to determine the minimum anesthetic concentration of isoflurane (MACISO) and sevoflurane (MACSEVO) and evaluate the cardiorespiratory changes induced by varying fractions of inspired oxygen (FiO2) in Magellanic penguins (Spheniscus magellanicus). Twenty adult penguins (3.53 ± 0.44 kg) of undetermined sex were used. Both MACISO (n = 9) and MACSEVO (n = 13) were established using an up-and-down design. Next, twelve mechanically ventilated penguins were maintained at 1 MACISO or 1 MACSEVO (n = 6 per group) with the FiO2 initially set at 1.0. Three FiO2 values (0.6, 0.4 and 0.2) were then held constant during anesthesia for 20 minutes each. Arterial blood samples were collected for gas analysis after the 20-minute period for each FiO2. Mean ± SD MACISO was 1.93 ± 0.10% and MACSEVO was 3.53 ± 0.13%. Other than heart rate at 0.6 FiO2 (86 ± 11 beats/minute in MACISO and 132 ± 37 beats/minute in MACSEVO; p = 0.041), no significant cardiorespiratory differences were detected between groups. In both groups, decreasing the FiO2 produced increased pH values and reduced partial pressures of carbon dioxide and bicarbonate. Partial pressures of oxygen (PaO2) gradually lowered from 1.0 FiO2 through 0.2 FiO2, though hypoxemia (PaO2 < 80 mmHg) occurred only with the latter FiO2. The MACISO and the MACSEVO for the Magellanic penguin fell within the upper range of reported avian MAC estimates. To prevent hypoxemia in healthy, mechanically ventilated, either isoflurane- or sevoflurane-anesthetized Magellanic penguins, a minimum FiO2 of 0.4 should be used.

Histological Alterations in the Internal Organs of Wistar Han Rats (Rattus norvegicus) Euthanized by Five Different Methods.

Selecting a method of euthanasia is an important step in designing research studies that use animals; euthanasia methods must be humane, cause minimal pain and suffering to the animal, and preserve the tissue architecture of the organs of interest. In this study, we evaluated the histomorphology of the internal organs (lung, spleen, heart, kidney, liver, brain, and adrenal gland) of rats submitted to five different methods of euthanasia, with the goal of determining which protocol caused the least alteration of histomorphology. Twenty adult Wistar Han rats (Rattus norvegicus) were divided into 5 groups of 4 rats each (2 females and 2 males) and were euthanized by CO2 or isoflurane inhalation, sodium thiopental or xylazine plus ketamine overdose, or decapitation. All euthanasia was performed in accordance with published guidelines and local legal require- ments. Necropsy was performed immediately after euthanasia. Specific internal organs were removed and placed in formalin and submitted for routine histologic processing. Histomorphological examination of hematoxylin and eosin-stained tissues revealed circulatory alterations in multiple organs, predominantly congestion in multiple tissues, pulmonary hemorrhage, and hepatic degeneration. The euthanasia methods that induced the most severe alterations were exposure to CO2 and anesthetic overdose with xylazine plus ketamine or sodium thiopental. Euthanasia by overexposure to isoflurane caused less damage, and the alterations were of minimal severity. Decapitation resulted in the lowest incidence of lesions in multiple organs but due its traumatic nature, it caused the highest incidence of pulmonary hemorrhage. In selecting a method of euthanasia, factors to consider are the species of animal, the purpose of the research, and the practical ability to perform the procedure to achieve maximal animal welfare without iatrogenic changes that could compromise the outcome and reproducibility of the study.

Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide.

AIMS: Pregnancy hypertension-induced endothelial dysfunction associated with impairment of nitric oxide (NO) bioavailability and hemodynamic derangements is a challenging for urgent procedures requiring maternal anesthesia. The volatile anesthetic isoflurane has demonstrated NO-associated protective effects. However, this isoflurane-induced effect is still unclear in pregnancy hypertension. Therefore, the present study examined the potential protective effects of isoflurane anesthesia on endothelial dysfunction and hemodynamic changes induced by hypertensive pregnancy associated with fetal and placental growth restrictions. MATERIALS AND METHODS: Animals were distributed into four groups: normotensive pregnant rats (Preg), anesthetized pregnant rats (Preg+Iso), hypertensive pregnant rats (HTN-Preg), and anesthetized hypertensive pregnant rats (HTN-Preg+Iso). Systolic and diastolic pressures, mean arterial pressure (MAP), heart rate, fetal and placental weights, vascular contraction, endothelium-derived NO-dependent vasodilation, and NO levels were assessed. The vascular endothelial growth factor (VEGF) levels and endothelial NO synthase (eNOS) Serine (1177) phosphorylation (p-eNOS) expression were also examined. KEY FINDINGS: Isoflurane produced more expressive hypotensive effects in the HTN-Preg+Iso versus Preg+Iso group, with respective reductions in MAP by 50 ± 13 versus 25 ± 4 mmHg (P < 0.05). Also, HTN-Preg+Iso compared to the HTN-Preg group showed (respectively) preventions against the weight loss of the fetuses (4.0 ± 0.6 versus 2.8 ± 0.6 g, P < 0.05) and placentas (0.37 ± 0.06 versus 0.30 ± 0.06 mg, P < 0.05), hyper-reactive vasocontraction response (1.8 ± 0.4 versus 2.8 ± 0.6 g, P < 0.05), impaired endothelium-derived NO-dependent vasodilation (84 ± 8 versus 50 ± 17 %, P < 0.05), reduced VEGF levels (147 ± 46 versus 25 ± 13 pg/mL, P < 0.05), and decreased p-eNOS expression (0.24 ± 0.07 versus 0.09 ± 0.05 arbitrary units, P < 0.05). SIGNIFICANCE: Isoflurane anesthesia protects maternal endothelial function in pregnancy hypertension, and possibly endothelium-derived NO is involved.

Activation of 5-HT3 receptors in the medulla oblongata is involved in the phasic control of urinary bladder.

The control of micturition depends on reflex mechanisms, however, it undergoes modulation from cortex, pons and medullary areas. This study investigated if the activation of 5-HT3 receptors in the medulla influences the urinary bladder (UB) regulation in rats. Isoflurane female Wistar rats were submitted to catheterization of the femoral artery and vein for mean arterial pressure (MAP) and heart rate (HR) recordings and injection of drugs, respectively. The UB was cannulated for intravesical pressure (IP) measurement. The Doppler flow probe was placed around the left renal artery for renal conductance (RC) recordings. Phenylbiguanide (PB) and granisetron (GN) were injected into the 4th brain ventricle in rats with guide cannulas implanted 5 days prior to the experiments; or PB and GN were randomly injected intravenously or applied topically (in situ) on the UB. PB injection into 4th V significantly increased IP (68.67 ± 11.70%) and decreased MAP (-29 ± 6 mmHg) compared to saline (0.34 ± 0.64% and -2 ± 2 mmHg), with no changes in the HR and RC. GN injection into the 4th V did not significantly change the IP and RC compared to saline, nevertheless, significantly increased MAP (25 ± 4 mmHg) and heart rate (36 ± 9 bpm) compared to saline. Intravenous PB and GN only produced cardiovascular effects, whilst PB but not GN in situ on the UB evoked increase in IP (111.60 ± 30.36%). Therefore, the activation of 5HT-3 receptors in medullary areas increases the intravesical pressure and these receptors are involved in the phasic control of UB. In contrast, 5-HT3 receptors in the medulla oblongata are involved in the pathways of the tonic control of the cardiovascular system. The activation of 5-HT3 receptors in the bladder cause increase in intravesical pressure and this regulation seem to be under phasic control as the blockade of such receptors elicits no changes in baseline intravesical pressure.

Sedative and cardiopulmonary effects of intramuscular combinations of hydromorphone, acepromazine, dexmedetomidine, and glycopyrrolate followed by intravenous propofol and inhalant isoflurane anesthesia in healthy dogs.

OBJECTIVE: To evaluate the sedative and cardiopulmonary effects of various combinations of acepromazine, dexmedetomidine, hydromorphone, and glycopyrrolate, followed by anesthetic induction with propofol and maintenance with isoflurane in healthy dogs. ANIMALS: 6 healthy adult female Beagles. PROCEDURES: Dogs were instrumented for hemodynamic measurements while anesthetized with isoflurane. Two hours after recovery, dogs received 1 of 4 IM combinations in a crossover design with 1 week between treatments: hydromorphone (0.1 mg/kg) and acepromazine (0.005 mg/kg; HA); hydromorphone and dexmedetomidine (0.0025 mg/kg; HD); hydromorphone, acepromazine, and dexmedetomidine (HAD); and hydromorphone, acepromazine, dexmedetomidine, and glycopyrrolate (0.02 mg/kg; HADG). Sedation was scored after 30 minutes. Physiologic variables and cardiac index were measured after sedation, after anesthetic induction with propofol, and every 15 minutes during maintenance of anesthesia with isoflurane for 60 minutes (target expired concentration at 760 mm Hg, 1.3%). RESULTS: Sedation scores were not significantly different among treatments. Mean ± SD cardiac index was significantly higher for the HA (202 ± 45 mL/min/kg) and HADG (185 ± 59 mL/min/kg) treatments than for the HD (88 ± 31 mL/min/kg) and HAD (103 ± 25 mL/min/kg) treatments after sedation and through the first 15 minutes of isoflurane anesthesia. No ventricular arrhythmias were noted with any treatment. CLINICAL RELEVANCE: In healthy dogs, IM administration of HADG before propofol and isoflurane anesthesia provided acceptable cardiopulmonary function with no adverse effects. This combination should be considered for routine anesthetic premedication in healthy dogs.

Effects of 7.2% hypertonic saline solution on cardiovascular parameters and endogenous arginine vasopressin secretion in euvolemic isoflurane-anesthetized horses.

OBJECTIVE: To compare the effects of 7.2% hypertonic and 0.9% isotonic saline (sodium chloride) solutions on cardiovascular parameters and plasma arginine vasopressin (AVP) concentrations in healthy, isoflurane-anesthetized horses. ANIMALS: 8 healthy horses. PROCEDURES: In a prospective, randomized, crossover study, horses were anesthetized with isoflurane twice with a 14-day washout period between anesthetic episodes. While anesthetized, horses received a bolus (4 mL/kg) of 7.2% hypertonic saline solution (HS) or 0.9% isotonic saline solution (IS). Heart rate; systolic, mean, and diastolic arterial blood pressures; and central venous and pulmonary artery pressures were measured every 5 minutes; cardiac output was measured by means of thermodilution every 15 minutes. Systemic vascular resistance (SVR) was calculated. Blood samples were collected before and during anesthesia, and plasma AVP concentrations were determined with a validated ELISA. Data were analyzed with repeated-measures ANOVA and Pearson correlations. RESULTS: HS caused an increase in systolic (P = .003) and mean (P = .023) arterial blood pressures that lasted for 30 minutes. The SVR was increased (P < .001) for 45 minutes with HS compared with the SVR after IS administration. Mean plasma AVP concentration increased (P = .03) 15 minutes after HS administration, with the increase lasting 90 minutes. CLINICAL RELEVANCE: A bolus of HS resulted in a clinically relevant increase in blood pressure in healthy, isoflurane-anesthetized horses. This effect was attributed to volume recruitment and an increase in SVR. Administration of HS offers an option for improving arterial blood pressure in anesthetized horses.

EVALUATION OF A LARYNGEAL MASK AIRWAY AS AN ALTERNATIVE TO OROTRACHEAL INTUBATION FOR MAINTAINING AIRWAY PATENCY DURING INHALANT ANESTHESIA UNDER SPONTANEOUS VENTILATION IN CAPYBARAS (HYDROCHOERUS HYDROCHAERIS).

Orotracheal intubation carries greater difficulty in rodents than in most domestic species. The human laryngeal mask airway (LMA) was compared with an endotracheal tube (ETtube) for maintaining airway patency in anesthetized capybaras (Hydrochoerus hydrochaeris). Six capybaras (24-52 kg) were remotely darted with intramuscular ketamine, midazolam, and acepromazine on two occasions (≥7-day intervals). After isoflurane mask induction for random placement of an ETtube or a LMA during each episode, anesthesia was maintained with isoflurane in oxygen under spontaneous ventilation for 90-120 min. Computed tomography of the pharynx and larynx was performed in two of six animals and three of six animals with the ETtube and LMA, respectively. End-tidal isoflurane [median (range)] was not significantly different between ETtube [0.6% (0.5-1.5%)] and LMA [0.6% (0.4-0.9%)]. Heart rate [67 ± 11 beats/min (ETtube) and 67 ± 18 beats/min (LMA)], mean arterial pressure [74 ± 13 mm Hg (ETtube) and 74 ± 14 mm Hg (LMA)], arterial CO2 tension [41 ± 2 mm Hg (ETtube) and 43 ± 4 mm Hg (LMA)], and arterial O2 tension [360 ± 59 mm Hg (ETtube) and 360 ± 63 mm Hg (LMA)] were not significantly different between treatment groups. Computed tomography showed gas in the esophagus with the LMA (three of three animals); the fit of the LMA to the larynx was adequate in two of three animals and fair in one of three animals. Recovery from anesthesia was uneventful. The LMA is a feasible alternative to the ETtube for maintaining airway patency during inhalant anesthesia in spontaneously breathing capybaras. However, the LMA may be dislodged during movement of the animal.

Lasting effects of ketamine and isoflurane administration on anxiety- and panic-like behavioral responses in Wistar rats.

In clinical and laboratory practice, the use of anesthetics is essential in order to perform surgeries. Anesthetics, besides causing sedation and muscle relaxation, promote several physiological outcomes, such as psychotomimetic alterations, increased heart rate, and blood pressure. However, studies depicting the behavioral effect induced by ketamine and isoflurane are conflicting. In the present study, we assessed the behavioral effects precipitated by ketamine and isoflurane administration. We have also evaluated the ketamine effect on cell cytotoxicity and viability in an amygdalar neuronal primary cell culture. Ketamine (80 mg/kg) caused an anxiogenic effect in rats exposed to the elevated T-maze test (ETM) 2 and 7 days after ketamine administration. Ketamine (40 and 80 mg/kg) administration also decreased panic-like behavior in the ETM. In the light/dark test, ketamine had an anxiogenic effect. Isoflurane did not change animal behavior on the ETM. Neither ketamine nor isoflurane changed the spontaneous locomotor activity in the open field test. However, isoflurane-treated animals explored less frequently the OF central area seven days after treatment. Neither anesthetic caused oxidative damage in the liver. Ketamine also reduced cellular metabolism and led to neuronal death in amygdalar primary cell cultures. Thus, our work provides evidence that ketamine and isoflurane induce pronounced long lasting anxiety-related behaviors in male rats.

Short or moderate-time exposure to the inhalational anesthetics isoflurane and sevoflurane does not alter the marble-burying behavior in mice.

Several studies suggest the involvement of glutamatergic neurotransmission in obsessive-compulsive disorder (OCD). Some NMDA glutamatergic receptor antagonists, such as the general anesthetic ketamine, have shown anti-OCD effects in preclinical and clinical studies. Therefore, we investigated whether the inhalational anesthetics isoflurane and sevoflurane, which are general anesthetics acting as NMDA receptor antagonists, would induce the same effects. To test our hypothesis, adult male Swiss mice were exposed to different concentrations of isoflurane (0.5, 1.5 or 3 %) or sevoflurane (0.8, 2.5 or 4 %) for 20 min (short-time exposure) or 1 h (moderate-time exposure) and submitted to the open field test (OFT) and the marble-burying test (MBT) in the same day (acute effect) or 7 days (long-lasting effect) after anesthetics administration. We found that single short or moderate-time exposure to isoflurane or sevoflurane, at sub-anesthetic or anesthetic concentrations, did not affect marble-burying behavior acutely or even 7 days after their administration. The same treatment schedules with isoflurane or sevoflurane did not impair total distance travelled in the OFT. A single moderate-time exposure to isoflurane (3 %) reduced, acutely, the central exploration of the open field, suggesting an anxiogenic-like effect of isoflurane in mice. Our results suggest that isoflurane and sevoflurane may not be promising anti-compulsive drugs.

New evidence for refinement of anesthetic choice in procedures preceding the forced swimming test and the elevated plus-maze.

Previous studies indicated that some general anesthetics induce long-term antidepressant and/or anxiolytic-like effects. This raises the concern about the use of anesthesia in surgeries that precede psychopharmacological tests, since it may be a potential bias on results depending on the experimental design used. Thus, we evaluated whether general anesthetics used in surgeries preceding psychopharmacological tests would affect rats behavior in tests predictive of antidepressant or anxiolytic-like effects. We tested if a single exposure to sub-anesthetic or anesthetic doses of tribromoethanol, chloral hydrate, thiopental or isoflurane would change rats behavior in the forced swimming test (FST) or in the elevated plus-maze (EPM) test, at 2 h or 7 days after their administration. We also evaluated whether prior anesthesia would interfere in the detection of the antidepressant-like effect of imipramine or the anxiolytic-like effect of diazepam. Previous anesthesia with the aforementioned anesthetics did not change rats behaviors in FST per se nor it changed the antidepressant-like effect induced by imipramine treatment. Rats previously anesthetized with tribromoethanol or chloral hydrate exhibited, respectively, anxiogenic-like and anxiolytic-like behaviors in the EPM. Prior anesthesia with thiopental or isoflurane did not produce any per se effect in rats behaviors in the EPM nor disturbed the anxiolytic-like effect of diazepam. Our results suggest that, in our experimental conditions, tribromoethanol and chloral hydrate are improper anesthetics for surgeries that precede behavioral analysis in the EPM. Isoflurane or thiopental may be suitable for anesthesia before evaluation in the EPM or in the FST.

Large Intracellular Domain-Dependent Effects of Positive Allosteric Modulators on Glycine Receptors.

Glycine receptors (GlyRs) are members of the pentameric ligand-gated ionic channel family (pLGICs) and mediate fast inhibitory neurotransmission in the brain stem and spinal cord. The function of GlyRs can be modulated by positive allosteric modulators (PAMs). So far, it is largely accepted that both the extracellular (ECD) and transmembrane (TMD) domains constitute the primary target for many of these PAMs. On the other hand, the contribution of the intracellular domain (ICD) to the PAM effects on GlyRs remains poorly understood. To gain insight about the role of the ICD in the pharmacology of GlyRs, we examined the contribution of each domain using a chimeric receptor. Two chimeras were generated, one consisting of the ECD of the prokaryotic homologue Gloeobacter violaceus ligand-gated ion channel (GLIC) fused to the TMD of the human α1GlyR lacking the ICD (Lily) and a second with the ICD (Lily-ICD). The sensitivity to PAMs of both chimeric receptors was studied using electrophysiological techniques. The Lily receptor showed a significant decrease in the sensitivity to four recognized PAMs. Remarkably, the incorporation of the ICD into the Lily background was sufficient to restore the wild-type α1GlyR sensitivity to these PAMs. Based on these data, we can suggest that the ICD is necessary to form a pLGIC having full sensitivity to positive allosteric modulators.

Effects of ketamine/xylazine and isoflurane on rat brain glucose metabolism measured by 18 F-fluorodeoxyglucose-positron emission tomography.

The aim of the present study was to investigate changes in glucose metabolism in male Wistar rats induced by the anesthetics isoflurane and ketamine combined with xylazine via 18 F-fluorodeoxyglucose-positron emission tomography. We analyzed the differential effects of the anesthetics on 18 F-fluorodeoxyglucose uptake and pharmacokinetics in 33 rats using quantification methods: (a) the standardized uptake value, (b) voxel-based analyses, and (c) kinetic analysis. Both anesthetics reduced glucose uptake in the entire brain. The voxel-based analyses detected smaller uptake reductions in the bilateral primary somatosensory system cortex and part of the limbic system in the ketamine-xylazine (KX) group and in the vestibular nucleus in the isoflurane group. Through kinetic analysis, we found that the volume of distribution and the membrane transport rate K1 were reduced in the KX group. Through various methods of 18 F-fluorodeoxyglucose-positron emission tomography quantification, the present study found that anesthesia with the ketamine-xylazine combination induced a global reduction of glucose metabolism compared with isoflurane; this reduction of metabolism was relatively lower in the primary somatosensory cortex and part of the limbic system. The volume of distribution of 18 F-fluorodeoxyglucose and its Glut1-mediated transport across the brain membranes (K1 ) were decreased in the KX group.

Cardiovascular and respiratory effects of lumbosacral epidural bupivacaine in isoflurane-anesthetized dogs: The effects of two volumes of 0.25% solution.

The purpose of this study was to compare cardiovascular and respiratory effects of two volumes of bupivacaine 0.25% (0.2 mL kg-1-treatment BUP02-and 0.4 mL kg-1 -treatment BUP04) administered epidurally at the lumbosacral intervertebral space in dogs anesthetized with isoflurane. This experimental prospective randomized crossover design trial used six mixed breed adult dogs, four neutered males and two spayed females. Each dog was anesthetized on three different occasions: the first for isoflurane minimum alveolar concentration (MAC) measurement, and the following two assigned treatments (BUP02 or BUP04). On the two treatment days, anesthesia was induced and maintained with isoflurane at 1.3 MAC during the experiments. Cardiovascular and respiratory measurements were recorded before (T0) and 5, 15, 30, 60 and 90 minutes after the epidural administration of bupivacaine. Comparisons between and within groups were performed by a mixed-model ANOVA and Friedman's test when appropriate followed by Bonferroni post-hoc test or Dunnet's test to compare time points within each treatment with T0 (p < 0.05). Mean arterial pressure decreased significantly from 15 to 90 minutes after the administration of BUP02 and from 5 to 60 minutes in BUP04, with lower values in BUP04 than in BUP02 lasting up to 30 minutes after bupivacaine administration. No significant changes in cardiac output and systemic vascular resistance were observed in either treatment. Hypoventilation was only detected in BUP04. Hemoglobin concentration and arterial oxygen content decreased after both treatment of bupivacaine with no significant decrease in oxygen delivery. Two dogs in BUP04 developed Horner's syndrome. The epidural administration of 0.4 mL.kg-1 of bupivacaine to dogs in sternal recumbency anesthetized with isoflurane 1.3 MAC caused more cardiovascular and respiratory depression than 0.2 mL.kg-1.

Clinical monitoring of cardiac output assessed by transoesophageal echocardiography in anaesthetised dogs: a comparison with the thermodilution technique.

BACKGROUND: Cardiac output (CO) is an important haemodynamic parameter to monitor in patients during surgery. However, the majority of the techniques for measuring CO have a limited application in veterinary practice due to their invasive approach and associated complexity and risks. Transoesophageal echocardiography (TEE) is a technique used to monitor cardiac function in human patients during surgical procedures and allows CO to be measured non-invasively. This prospective clinical study aimed to compare the transoesophageal echocardiography using a transgastric view of the left ventricular outflow tract (LVOT) and the thermodilution (TD) technique for the assessment of CO during mean arterial pressure of 65-80 mmHg (normotension) and <65 mmHg (hypotension) in dogs undergoing elective surgery. Eight dogs were pre-medicated with acepromazine (0.05 mg/kg, IM), tramadol (4 mg/kg, IM) and atropine (0.03 mg/kg, IM), followed by anaesthetic induction with propofol (3-5 mg/kg IV) and maintenance with isoflurane associated with a continuous infusion rate of fentanyl (bolus of 3 µg/kg followed by 0.3 µg/kg/min). The CO was measured by TEE (COTEE) and TD (COTD) at the end of expiration during normotension and hypotension (induced by isoflurane). RESULTS: There was a strong positive correlation between COTEE and COTD ​​(r = 0.925; P < 0.0001). The bias between COTD and COTEE was 0.14 ± 0.29 L/min (limits of agreement, -0.44 to 0.72 L/min). The percentage error of CO measured by the two methods was 12.32%. In addition, a strong positive correlation was found between COTEE and COTD during normotension (r = 0.995; P < 0.0001) and hypotension (r = 0.78; P = 0.0223). CONCLUSIONS: The results of this study indicated that the transgastric view of the LVOT by TEE was a minimally invasive alternative to clinically monitoring CO in dogs during anaesthesia. However, during hypotension, the CO obtained by TEE was less reliable, although still acceptable.

Effects of a single intravenous bolus of fentanyl on the minimum anesthetic concentration of isoflurane in chickens (Gallus gallus domesticus).

OBJECTIVE: To assess the temporal effects of a single fentanyl intravenous (IV) bolus on the minimum anesthetic concentration (MAC) of isoflurane in chickens and to evaluate the effects of this combination on heart rate (HR) and rhythm, systemic arterial pressures (sAP) and ventilation. STUDY DESIGN: Prospective experimental trial. ANIMALS: Seventeen adult chickens weighing 1.8±0.2 kg. METHODS: Individual isoflurane MAC for 17 chickens was previously determined using the bracketing method. Chickens were anesthetized with isoflurane to evaluate the effects of a single IV fentanyl bolus (10 or 30 µg kg-1) on isoflurane MAC over time using the up-and-down method. Ventilation was controlled. The isoflurane MAC reduction was estimated by logistic regression at 5 and 15 minutes after fentanyl administration. In the second phase, seven chickens were anesthetized with isoflurane, and fentanyl was administered (30 µg kg-1) IV over 1 minute during spontaneous ventilation and HR and rhythm, sAP and ventilation variables were measured. RESULTS: At 5 minutes after IV administration of fentanyl (10 or 30 µg kg-1), isoflurane MAC was significantly reduced by 17.6% (6.1-29.1%) [logistic regression estimate (95% Wald confidence interval)] and 42.6% (13.3-71.9%), respectively. Isoflurane MAC reduction at 15 minutes after IV administration of fentanyl (10 or 30 µg kg-1) was 6.2% (-0.6 to 12.9%) and 13.2% (-0.9 to 27.3%), respectively; however, this reduction was not significant. No clinically significant cardiopulmonary changes or arrhythmias were detected after the administration of fentanyl (30 µg kg-1). CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a single fentanyl bolus induced a dose-dependent and short-lasting reduction in isoflurane MAC. The higher dose induced no significant cardiopulmonary depression in isoflurane-anesthetized chickens during spontaneous ventilation. In chickens anesthetized with isoflurane, the clinical usefulness of a single fentanyl bolus is limited by its short duration of effect.

Cyclosporine A attenuates apoptosis and necrosis after ischemia-reperfusion-induced renal injury in transiently hyperglycemic rats.

PURPOSE:: To investigate the effects of cyclosporine A on renal ischemia-reperfusion injury during transient hyperglycemia in rats. METHODS:: In a model of ischemia-reperfusion-induced renal injury and transiently induced hyperglycemia by intraperitoneal injection of glucose, 2.5 g.kg-1, Wistar rats were anesthetized with either isoflurane or propofol and received intravenous cyclosporine A, 5 mg.kg-1, five minutes before reperfusion. Comparison groups were isoflurane and propofol sham groups and isoflurane and propofol ischemia-reperfusion-induced renal injury. Renal tubular cell viability was quantitatively assessed by flow cytometry after cell culture and classified as early apoptosis, necrotic cells, and intact cells. RESULTS:: Early apoptosis was significantly higher in isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury when compared to both cyclosporine A treated and sham groups. Necrosis percentage was significantly higher in propofol-anesthetized animals subjected to renal ischemia-reperfusion injury. The percentage of intact cells was lower in both, isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury. CONCLUSION:: In a model of ischemia-reperfusion-induced renal injury, cyclosporine A, 5 m.kg-1, administered five minutes before renal reperfusion in rats with acute-induced hyperglycemia under either isoflurano or propofol anesthesia, attenuated early apoptosis and preserved viability in renal tubular cells, regardless of the anesthetic used.