Minimum Alveolar Concentration Of Isoflurane Research Articles

The Role of MicroRNA in Anesthetic‐Induced Cardiac Preconditioning

Anesthetic preconditioning has been reported to decrease myocardial infarct size after ischemia‐reperfusion injury. However, the underlying mechanisms are not fully understood. MicroRNAs (miRNAs) are short nucleotide sequences that have been implicated in many different cell signaling pathways via suppression of messenger RNA. In this study, we investigated the effect of anesthetic exposure on miRNA expression in the left ventricle of the rat heart. Male Wistar rats were exposed to 30 min of one minimum alveolar concentration of isoflurane. Total RNA was extracted from the left ventricle of the heart and converted to cDNA. Using real‐time PCR, microarray‐based analyses of 88 miRNAs were performed, revealing twenty upregulated miRNAs. One microRNA, miR‐21, has consistently shown a twofold upregulation in hearts exposed to anesthetic. This microRNA has been demonstrated to decrease infarct size in hearts exposed to ischemic preconditioning via its action on heat shock protein 70, endothelial nitric oxide synthase, and inducible nitric oxide synthase. Further investigation into the isoflurane‐induced upregulation of miR‐21 may reveal that miR‐21‐mediated pathways contribute to the preconditioning effect of anesthetics. This work is supported by NIH Grants R01HL034708 and P01GM066730 for Z. Bosnjak.

Determination of Minimum Alveolar Concentration for Isoflurane and Sevoflurane in a Rodent Model of Human Metabolic Syndrome

Morbid obesity affects the pharmacokinetics and pharmacodynamics of anesthetics, which may result in inappropriate dosing. We hypothesized that obesity significantly alters the minimum alveolar concentration (MAC) for isoflurane and sevoflurane. To test this hypothesis, we used a rodent model of human metabolic syndrome developed through artificial selection for inherent low aerobic capacity runners (LCR) and high aerobic capacity runners (HCR). The LCR rats are obese, display phenotypes homologous to those characteristic of human metabolic syndrome, and exhibit low running endurance. In contrast, HCR rats have high running endurance and are characterized by improved cardiovascular performance and overall health. Male and female LCR (n = 10) and HCR (n = 10) rats were endotracheally intubated and maintained on mechanical ventilation with either isoflurane or sevoflurane. A bracketing design was used to determine MAC; sensory stimulation was induced by tail clamping. An equilibration period of 30 minutes was provided before and between the consecutive tail clamps. Two-tailed parametric (unpaired t test) and nonparametric (Mann-Whitney test) statistics were used for the comparison of MAC between LCR and HCR rats. The data are reported as mean ± sd along with the 95% confidence interval. A P value of <0.05 was considered statistically significant. The MAC for isoflurane in LCR rats (1.52% ± 0.13%) was similar to previously reported isoflurane-MAC for normal rats (1.51% ± 0.12%). The HCR rats showed a significantly higher isoflurane-MAC (1.90% ± 0.19%) than did the LCR rats (1.52% ± 0.13%) (P = 0.0001). The MAC for sevoflurane was not significantly different between LCR and HCR rats and was similar to the previously published sevoflurane-MAC for normal rats (2.4% ± 0.30%). There was no influence of sex on the MAC of either isoflurane or sevoflurane. Obesity and associated comorbidities do not affect anesthetic requirements as measured by MAC in a rodent model of metabolic syndrome. By contrast, high aerobic capacity is associated with a higher MAC for isoflurane and may be a risk factor for subtherapeutic dosing.

Isoflurane enhances the expression of cytochrome C by facilitation of NMDA receptor in developing rat hippocampal neurons in vitro

This study examined the effects of clinically relevant concentrations of isoflurane on the amplitude of NMDA receptor current (I(NMDA)) and the expression of cytochrome C in cultured developing rat hippocampal neurons. The hippocampi were dissected from newborn Sprague-Dawley rats. Hippocampal neurons were primarily cultured for 5 days and then treated with different concentrations of isoflurane [(0.25, 0.5, 0.75, 1 minimum alveolar concentration (MAC))]. The peak of I(NMDA) was recorded by means of the whole cell patch clamp technique. The cytochrome C level was detected by Western blotting and quantitative real-time PCR. Our results showed that isoflurane (0.25, 0.5, 0.75 and 1 MAC) potentiated the amplitude of I(NMDA) by (116 ± 8.8)%, (122 ± 11.7)%, (135 ± 14.3)% and (132 ± 14.6)%, respectively, and isoflurane increased the mRNA expression of cytochrome C in a concentration-dependent manner. The cytochrome C mRNA expression reached a maximum after 0.5 MAC isoflurane stimulation for 6 h (P<0.05). It was concluded that isoflurane enhances the expression of cytochrome C in cultured rat hippocampal neurons, which may be mediated by facilitation of NMDA receptor.

Comparison of the effects of epidural or intravenous methadone on the minimum alveolar concentration of isoflurane in dogs

The effects of epidural and intravenous (IV) methadone (0.5mg/kg) on the minimum alveolar concentration of isoflurane (ISO(MAC)) were compared in dogs. Six dogs (16.5 ± 2.5 kg bodyweight) received three treatments in random order during isoflurane anaesthesia, with a 7 day washout interval between each study. Methadone was injected via a lumbosacral epidural catheter introduced 10 cm cranially into the epidural canal and the electrical stimulation for ISO(MAC) determination was applied either to the thoracic (EP(T) treatment) or to the pelvic limb (EP(P) treatment) during separate study days. In the IV treatment, ISO(MAC) was determined via electrical stimulation of the pelvic limb. Variables were recorded before (baseline), 2.5 and 5h after drug injection. The ISO(MAC) decreased significantly (P<0.05) from baseline at 2.5 and 5h after methadone in all treatments. At 2.5h, the magnitude of ISO(MAC) reduction did not differ between treatments (mean decreases from baseline: 30-33%). The ISO(MAC) reduction lasted longer following epidural methadone in the thoracic limb (decreases from baseline: 30% at 5h in the EP(T) treatment vs. 19% and 16% in the EP(P) and IV treatments, respectively). Although the isoflurane sparing effect provided by epidural methadone was not significantly greater than IV methadone during the initial stage (2.5h), it was more prolonged than the IV route in specific dermatomes (5h in the thoracic limb) with the epidural technique employed. Methadone may therefore provide a greater isoflurane sparing effect when administered epidurally, compared to IV, when noxious stimulation occurs in specific dermatomes.

Effects of constant rate infusion of lidocaine and ketamine, with or without morphine, on isoflurane MAC in horses

Lidocaine and ketamine are administered to horses as a constant rate infusion (CRI) during inhalation anaesthesia to reduce anaesthetic requirements. Morphine decreases the minimum alveolar concentration (MAC) in some domestic animals; when administered as a CRI in horses, morphine does not promote haemodynamic and ventilatory changes and exerts a positive effect on recovery. Isoflurane-sparing effect of lidocaine, ketamine and morphine coadministration has been evaluated in small animals but not in horses. To determine the reduction in isoflurane MAC produced by a CRI of lidocaine and ketamine, with or without morphine. Addition of morphine to a lidocaine-ketamine infusion reduces isoflurane requirement and morphine does not impair the anaesthetic recovery of horses. Six healthy adult horses were anaesthetised 3 times with xylazine (1.1 mg/kg bwt i.v.), ketamine (3 mg/kg bwt i.v.) and isoflurane and received a CRI of lidocaine-ketamine (LK), morphine-lidocaine-ketamine (MLK) or saline (CTL). The loading doses of morphine and lidocaine were 0.15 mg/kg bwt i.v and 2 mg/kg bwt i.v. followed by a CRI at 0.1 mg/kg bwt/h and 3 mg/kg bwt/h, respectively. Ketamine was given as a CRI at 3 mg/kg bwt/h. Changes in MAC characterised the anaesthetic-sparing effect of the drug infusions under study and quality of recovery was assessed using a scoring system. Mean isoflurane MAC (mean ± s.d.) in the CTL, LK and MLK groups was 1.25 ± 0.14%, 0.64 ± 0.20% and 0.59 ± 0.14%, respectively, with MAC reduction in the LK and MLK groups being 49 and 53% (P<0.001), respectively. No significant differences were observed between groups in recovery from anaesthesia. Administration of lidocaine and ketamine via CRI decreases isoflurane requirements. Coadministration of morphine does not provide further reduction in anaesthetic requirements and does not impair recovery.

GABAA receptor antagonism increases NMDA receptor inhibition by isoflurane at a minimum alveolar concentration

ObjectiveAt the minimum alveolar concentration (MAC), isoflurane potentiates GABAA receptor currents and inhibits NMDA receptor currents, and these actions may be important for producing anesthesia. However, isoflurane modulates GABAA receptors more potently than NMDA receptors. The objective of this study was to test whether isoflurane would function as a more potent NMDA receptor antagonist if its efficacy at GABAA receptors was decreased. Study designProspective experimental study. AnimalsFourteen 10-week-old male Sprague–Dawley rats weighing 269 ± 12 g. MethodsIndwelling lumbar subarachnoid catheters were surgically placed in isoflurane-anesthetized rats. Two days later, the rats were anesthetized with isoflurane, and artificial CSF containing either 0 or 1 mg kg−1 picrotoxin, a GABAA receptor antagonist, was infused intrathecally at 1 μL minute−1. The baseline isoflurane MAC was then determined using a standard tail clamp technique. MK801 (dizocilpine), an NMDA receptor antagonist, was then administered intravenously at 0.5 mg kg−1. Isoflurane MAC was re-measured. ResultsPicrotoxin increased isoflurane MAC by 16% compared to controls. MK801 significantly decreased isoflurane MAC by 0.72% of an atmosphere in controls versus 0.47% of an atmosphere in rats receiving intrathecal picrotoxin. Conclusions and clinical relevanceA smaller MK801 MAC-sparing effect in the picrotoxin group is consistent with greater NMDA antagonism by isoflurane in these animals, since it suggests that fewer NMDA receptors are available upon which MK801 could act to decrease isoflurane MAC. Decreasing isoflurane GABAA potentiation increases isoflurane NMDA antagonism at MAC. Hence, the magnitude of an anesthetic effect on a given channel or receptor at MAC may depend upon effects at other receptors.

Effect of dexmedetomidine on the minimum alveolar concentration of isoflurane in cats

This study reports the effects of dexmedetomidine on the minimum alveolar concentration of isoflurane (MAC(iso) ) in cats. Six healthy adult female cats were used. MAC(iso) and dexmedetomidine pharmacokinetics had previously been determined in each individual. Cats were anesthetized with isoflurane in oxygen. Dexmedetomidine was administered intravenously using target-controlled infusions to maintain plasma concentrations of 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, and 20 ng/mL. MAC(iso) was determined in triplicate at each target plasma dexmedetomidine concentration. Blood samples were collected and analyzed for dexmedetomidine concentration. The following model was fitted to the concentration-effect data: [Formula in text] where MAC(iso.c) is MAC(iso) at plasma dexmedetomidine concentration C, MAC(iso.0) is MAC(iso) in the absence of dexmedetomidine, I(max) is the maximum possible reduction in MAC(iso), and IC(50) is the plasma dexmedetomidine concentration producing 50% of I(max). Mean ± SE MAC(iso.0), determined in a previous study conducted under conditions identical to those in this study, was 2.07 ± 0.04. Weighted mean ± SE I(max), and IC(50) estimated by the model were 1.76 ± 0.07%, and 1.05 ± 0.08 ng/mL, respectively. Dexmedetomidine decreased MAC(iso) in a concentration-dependent manner. The lowest MAC(iso) predicted by the model was 0.38 ± 0.08%, illustrating that dexmedetomidine alone is not expected to result in immobility in response to noxious stimulation in cats at any plasma concentration.

Effects of fentanyl on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats

The effects of fentanyl on the minimum alveolar concentration (MAC) of isoflurane and cardiovascular function in mechanically ventilated goats were evaluated using six healthy goats (three does and three wethers)....

A Comparison of 1 Minimum Alveolar Concentration Desflurane and 1 Minimum Alveolar Concentration Isoflurane Anesthesia in Patients Undergoing Craniotomy for Supratentorial Lesions

Background A critical point in craniotomy is during opening of the dura and the subsequent potential for cerebral edema. Use of desflurane in neurosurgery may be beneficial because it facilitates early postoperative neurologic evaluation; however, data on the effect of desflurane on intracranial pressure in humans are limited. Isoflurane has been used extensively in neurosurgical patients. Objective This study compared 1 minimum alveolar concentration (MAC) desflurane with 1 MAC isoflurane in facilitating hemodynamic stability, brain relaxation, and postoperative recovery characteristics in patients who underwent craniotomy for supratentorial lesions. Methods A total of 70 patients (aged 18–65 years), with American Society of Anesthesiologists (ASA) 1 or 2 physical status, who underwent craniotomy for supratentorial lesions, were enrolled in the study. For induction of anesthesia, fentanyl (2 μg/kg IV) and propofol (2 mg/kg IV) were administered. Endotracheal intubation was performed after administration of vecuronium (0.1 mg/kg IV) for total muscle relaxation. Before insertion of the skull pins, additional fentanyl (2 μg/kg IV) was administered. Patients were randomly allocated to 1 of 2 anesthetic regimens. For maintenance of anesthesia, 35 patients received 1 MAC of desflurane (group 1) and 35 patients received 1 MAC of isoflurane (group 2) within 50% oxygen in nitrous oxide. Intraoperatively, heart rate (HR) and mean arterial pressure (MAP) were measured and recorded before induction and 1 minute after induction, after endotracheal intubation, before skull pin insertion and 1 minute after skull pin insertion, before incision and 1 minute after incision, and before extubation and 1 minute after extubation. Also, HR and MAP were recorded at 30-minute intervals. Postoperatively, extubation time, eye opening time to verbal stimuli, orientation time, and time to reach an Aldrete postanesthetic recovery score of ≥8 were recorded. In addition, opioid consumption was calculated and recorded. Brain relaxation was evaluated according to a 4-step brain relaxation scoring scale. All outcomes of the study were assessed and recorded by an anesthesiologist blinded to the volatile anesthetic gases studied. Results No significant difference in HR was observed between the 2 groups. Intraoperative MAP values in group 1 were higher than in group 2 ( P < 0.05). No significant difference was found between these groups in brain relaxation and opioid consumption. Extubation time, eye opening time to verbal stimuli, and time to reach an Aldrete score of ≥8 were found to be significantly shorter in patients in group 1 compared with patients in group 2 ( P < 0.05). Conclusions In patients who underwent craniotomy for supratentorial lesions, patients who received 1 MAC desflurane–based anesthesia had earlier postoperative cognitive recovery and postoperative neurologic examination compared with patients who received 1 MAC isoflurane–based anesthesia. The observed benefits of early recovery from anesthesia, however, should be considered with risks such as higher MAP in patients administered 1 MAC desflurane.

Effects of midazolam on isoflurane minimum alveolar concentration in goats

The effects of midazolam on the minimum alveolar concentration (MAC) of isoflurane in mechanically ventilated goats were evaluated. Six healthy goats (3 does and 3 wethers) were used in a randomized crossover design. General anaesthesia was induced with isoflurane. Endotracheal intubation was performed after which anaesthesia was maintained with isoflurane. Baseline isoflurane MAC was determined. The goats then received, on separate occasions, one of three midazolam treatments intravenously: bolus dose of 0.1 mg/kg followed by a maintenance dose of 0.1 mg/kg/h (Treatment LMID), bolus dose of 0.3 mg/kg followed by a maintenance dose of 0.3 mg/kg/h (Treatment MMID), bolus dose of 0.9 mg/kg followed by a maintenance dose of 0.9 mg/kg/h (Treatment HMID) intravenously. Isoflurane MAC was then re-determined for each midazolam treatment. The baseline [median (inter-quartile range)] isoflurane MAC in goats was 1.40 (1.38–1.41)%. Baseline isoflurane MAC was statistically significantly reduced ( P < 0.05) following Treatment LMID, Treatment MMID and Treatment HMID by 16.8%, 35.1% and 54.7%, respectively. Quality of recovery from anaesthesia was good following all midazolam treatments. Midazolam, administered by constant rate infusion, significantly reduces isoflurane MAC in goats.

Isoflurane Enhances Reactive Oxygen Species Generation via Attenuation of Complex I

BACKROUND: Reactive oxygen species (ROS) mediate anesthetic-induced protection of the heart from ischemia and reperfusion injury (anesthetic preconditioning, APC), but the precise role and mechanism of ROS generation remain unknown. In this study, we tested if a mitochondria-targeted mimetic of superoxide dismutase (mito-tempol, MT) can abolish the reduction in myocardial infarct size afforded by the volatile anesthetic isoflurane. Further, we investigated the mechanism by which isoflurane generates ROS in isolated mitochondria and submitochondrial particles. METHODS: Rats received 0.9% saline (control) or 3.0 mg/kg MT with or without exposure to 1 minimum alveolar concentration isoflurane for 30 min. Myocardial infarction was performed by left anterior descending artery occlusion for 30 min followed by 2 h reperfusion. Infarct size was measured by patent blue and triphenyltetrazolium chloride staining. Mitochondrial ROS production was measured spectrofluorometrically in isolated mitochondria and submitochondrial particles using the fluorescent probe amplex red. The effect of isoflurane on mitochondrial respiratory complex enzyme activities was determined spectrophotometrically in cholic acid-solubilized mitochondria. RESULTS: APC reduced infarct size of the left ventricular area at risk (mean±SD=40±9%) relative to the control (60±4%). MT abolished cardioprotection (60±9%) afforded by APC. Isoflurane enhanced mitochondrial ROS production induced by antimycin A or oxidized ubiquinone in the presence of substrates pyruvate and malate, but not succinate. Isoflurane also produced ROS at Complex I in the absence of any inhibitors in submitochondrial particles. Mitochondrial respiration and electron transport chain complex assays revealed that isoflurane only inhibits complex I activity. CONCLUSIONS: These results highlight that ROS are critical for APC. Moreover, the results indicate that isoflurane produces ROS at complex I and enhances ROS generation at complex III of the respiratory chain via its effect to attenuate complex I activity.

Effect of dexmedetomidineon minimum alveolar concentration of isoflurane required to inhibit the body movementduring skin incision

：Objective To investigatethe effect of dexmedetomidine on minimum alveolar concentration (MAC) of isofluranerequired to inhibit the body movement during skin incision. Methods Forty-eight ASA Ⅰ or Ⅱ patients aged 40-60 yr withbody mass index of 22-27 kg/m2 undergoing elective upper abdominal surgery under generalanesthesia were randomly divided into 3 groups: control group (group C, n = 15);low dosedexmedetomidine group (group D1, n = 17) and high dose dexmedetomidine group (group D2, n= 16). The patients were unpremedicated. Dexmedetomidine 0.4 and 0.8 μg/kgin normal saline (NS) 15 ml was infused over 15 min before induction of anesthesia in D1and D2 groups respectively. Anesthesia was induced with fentanyl-propofol-succinylcholine.The patients were mechanically ventilated after tracheal intubation. Anesthesia wasmaintained with isoflurane. MAC of isoflurane was determined by up-and-down technique. Theinitial end-tidal isofiurane concentration was set at 1.0%, 0.8% and 0.6% in C, D1 and D2groups respectively. Each time the end-tidal isoflurane concentration wasincreased/decreased by 0.2%. Skin incision was made after 15 min of equilibration, whenthe twitch height returned to more than 90% of its control value. Movement of body andlimbs including swallowing and coughing were carefully looked for when skin incision wasmade. MAC of isoflurane was the mean of end-tidal concentration of isoflurane of eachcrossover pair, and 95 % CI was calculated. Results MAC of isoflurane was significantlydecreased in D1 and D2 groups as compared with group C and in group D2 as compared withgroup D1( P ＜ 0.05or 0.01 ). Conclusion Dexmedetomidine can significantly decrease MAC of isofluranerequired to inhibit the body movement during skin incision in a dose-dependent manner. Key words: Dexmedetomidine; Dose-response relationship, drug; Isoflurane

Effects of propofol on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats

ObjectiveTo evaluate the effects of propofol, on isoflurane minimum alveolar concentration (MAC) and cardiovascular function in mechanically ventilated goats. Study designProspective, randomized, crossover experimental study. AnimalsSix goats, three does and three wethers. MethodsGeneral anaesthesia was induced with isoflurane in oxygen. Following endotracheal intubation, anaesthesia was maintained with isoflurane in oxygen. Intermittent positive pressure ventilation was applied. Baseline isoflurane MAC was determined, the noxious stimulus used being clamping a claw. The goats then received, on separate occasions, three propofol treatments intravenously: bolus of 0.5 mg kg−1 followed by a constant rate infusion (CRI) of 0.05 mg kg−1 minute−1 (treatment LPROP); bolus of 1.0 mg kg−1 followed by a CRI of 0.1 mg kg−1 minute−1 (treatment MPROP), bolus of 2.0 mg kg−1 followed by a CRI of 0.2 mg kg−1 minute−1 (treatment HPROP). Isoflurane MAC was re-determined following propofol treatments. Plasma propofol concentrations at the time of MAC confirmation were measured. Cardiopulmonary parameters were monitored throughout the anaesthetic period. Quality of recovery was scored. The Friedman test was used to test for differences between isoflurane MACs. Medians of repeatedly measured cardiovascular parameters were tested for differences between and within treatments using repeated anova by ranks (p < 0.05 for statistical significance). ResultsIsoflurane MAC [median (interquartile range)] was 1.37 (1.36–1.37) vol%. Propofol CRI significantly reduced the isoflurane MAC, to 1.15 (1.08–1.15), 0.90 (0.87–0.93) and 0.55 (0.49–0.58) vol% following LPROP, MPROP and HPROP treatment, respectively. Increasing plasma propofol concentrations strongly correlated (Spearman rank correlation) with decrease in MAC (Rho = 0.91). Cardiovascular function was not affected significantly by propofol treatment. Quality of recovery was satisfactory. Conclusions and clinical relevanceIn goats, propofol reduces isoflurane MAC in a dose-dependent manner with minimal cardiovascular effects.

Discrete Change in Volatile Anesthetic Sensitivity in Mice with Inactivated Tandem Pore Potassium Ion Channel TRESK

We investigated the role of tandem pore potassium ion channel (K2P) TRESK in neurobehavioral function and volatile anesthetic sensitivity in genetically modified mice. Exon III of the mouse TRESK gene locus was deleted by homologous recombination using a targeting vector. The genotype of bred mice (wild type, knockout, or heterozygote) was determined using polymerase chain reaction. Morphologic and behavioral evaluations of TRESK knockout mice were compared with wild-type littermates. Sensitivity of bred mice to isoflurane, halothane, sevoflurane, and desflurane were studied by determining the minimum alveolar concentration preventing movement to tail clamping in 50% of each genotype. With the exception of decreased number of inactive periods and increased thermal pain sensitivity (20% decrease in latency with hot plate test), TRESK knockout mice had healthy development and behavior. TRESK knockout mice showed a statistically significant 8% increase in isoflurane minimum alveolar concentration compared with wild-type littermates. Sensitivity to other volatile anesthetics was not significantly different. Spontaneous mortality of TRESK knockout mice after initial anesthesia testing was nearly threefold higher than that of wild-type littermates. TRESK alone is not critical for baseline central nervous system function but may contribute to the action of volatile anesthetics. The inhomogeneous change in anesthetic sensitivity corroborates findings in other K2P knockout mice and supports the theory that the mechanism of volatile anesthetic action involves multiple targets. Although it was not shown in this study, a compensatory effect by other K2P channels may also contribute to these observations.

Isoflurane pre-treatment before cardiopulmonary bypass alleviates neutrophil accumulation in dog lungs

This study investigated the effect of isoflurane pretreatment on cardiopulmonary bypass (CPB)-related lung injury. Twelve dogs were randomly divided into two groups of six each. In one group, 1.0 minimum alveolar concentration (MAC) of isoflurane was dministered for 30 min before CPB, while the control group received no anaesthetic. Both groups then underwent 100 min of mild hypothermic CPB with 60-min aortic cross clamping. Haemodynamic parameters, respiratory mechanics and alveolar arterial oxygen difference (AaDO₂) were measured during the experiment. One hundred and fifty minutes after CPB, lung tissue samples from the non-dependent and dependent portions of the left and right lungs were harvested for polymorphonulear leukocyte (PMNs) counts. Following CPB, within the control group, pulmonary vascular resistance (PVR) was significantly increased at 60, 120 and 180 min after declamping, AaDO₂ deteriorated at 180 min post-declamping, and dynamic lung compliance (DLC) was reduced dramatically after declamping. Isoflurane pretreatment before CPB significantly reduced PVR compared to the controls. AaDO₂ was impaired at 180 min after declamping and DLC was decreased after declamping within the isoflurane group. No differences in AaDO₂ and DLC were found between the isoflurane and control groups. At 180 min after declamping, the PMN count in both the non-dependent and dependent regions of the isoflurane pre-treated lungs was significantly lower than that of the controls. Our results suggest that 30-min pre-treatment with 1.0 MAC isoflurane before CPB caused a reduction in PMN accumulation in the dog lungs, inhibition of increases in PVR, and it did not affect AaDO₂ in the early post-CPB stage.

Acute Hemodynamic Changes After Rapid Intravenous Bolus Dosing of Dexmedetomidine in Pediatric Heart Transplant Patients Undergoing Routine Cardiac Catheterization

Dexmedetomidine is a highly selective α(2)-adrenoceptor agonist with sedative, anxiolytic, and analgesic properties that has minimal effects on respiratory drive. Its sedative and hypotensive effects are mediated via central α(2A) and imidazoline type 1 receptors while activation of peripheral α(2B)-adrenoceptors result in an increase in arterial blood pressure and systemic vascular resistance. In this randomized, prospective, clinical study, we attempted to quantify the short-term hemodynamic effects resulting from a rapid i.v. bolus administration of dexmedetomidine in pediatric cardiac transplant patients. Twelve patients, aged 10 years or younger, weighing ≤40 kg, presenting for routine surveillance of right and left heart cardiac catheterization after cardiac transplantation were enrolled. After an inhaled or i.v. induction, the tracheas were intubated and anesthesia was maintained with 1 minimum alveolar concentration of isoflurane in room air, fentanyl (1 μg/kg), and rocuronium (1 mg/kg). At the completion of the planned cardiac catheterization, 100% oxygen was administered. After recording a set of baseline values that included heart rate (HR), systolic blood pressure, diastolic blood pressure, central venous pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and thermodilution-based cardiac output, a rapid i.v. dexmedetomidine bolus of either 0.25 or 0.5 μg/kg was administered over 5 seconds. The hemodynamic measurements were repeated at 1 minute and 5 minutes. There were 6 patients in each group. Investigation suggested that systolic blood pressure, diastolic blood pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and systemic vascular resistance all increased at 1 minute after rapid i.v. bolus for both doses and decreased significantly to near baseline for both doses by 5 minutes. The transient increase in pressures was more pronounced in the systemic system than in the pulmonary system. In the systemic system, there was a larger percent increase in the diastolic pressures than the systolic pressures. Cardiac output, central venous pressure, and pulmonary vascular resistance did not change significantly. HR decreased at 1 minute for both doses and was, within the 0.5 μg/kg group, the only hemodynamic variable still changed from baseline at the 5-minute time point. Rapid i.v. bolus administration of dexmedetomidine in this small sample of children having undergone heart transplants was clinically well tolerated, although it resulted in a transient but significant increase in systemic and pulmonary pressure and a decrease in HR. In the systemic system, there is a larger percent increase in the diastolic pressures than the systolic pressures and, furthermore, these transient increases in pressures were more pronounced in the systemic system than in the pulmonary system.

Effects of perzinfotel, butorphanol tartrate, and a butorphanol-perzinfotel combination on the minimum alveolar concentration of isoflurane in cats

To determine the effects of perzinfotel, butorphanol, and their combination on the minimal alveolar concentration (MAC) of isoflurane in cats. 7 healthy sexually intact cats (4 males and 3 females), aged 12 to 17 months and weighing 2.8 to 4.6 kg. In a crossover design, saline (0.9% NaCl) solution, perzinfotel (2.5 to 15 mg/kg; IV, IM, and SC), butorphanol tartrate (0.2 mg/kg, IM), or a combination of 5 mg of perzinfotel/kg and 2 mg of butorphanol tartrate/kg (both IM) was administered to 6 cats before 7 separate episodes of anesthesia with isoflurane in oxygen. Heart rate, arterial blood pressure, bispectral index (BIS), and inspiration and expiration concentrations of isoflurane were continuously monitored. The isoflurane MAC was determined twice during anesthesia. IV, IM, and SC administration of perzinfotel at 2.5 to 15 mg/kg resulted in a significant decrease in mean isoflurane MAC by 43.3% to 68.0%. The BIS significantly increased after perzinfotel administration via the same routes at 2.5 to 15 mg/kg and after perzinfotel-butorphanol administration IM. Blood pressure was significantly higher after perzinfotel was administered at 5 mg/kg, IM; 10 mg/kg, IV; and 10 mg/kg, SC than after saline solution administration. Perzinfotel administration decreased the isoflurane MAC and increased several BIS and blood pressure values in anesthetized cats. Administration of perzinfotel prior to isoflurane anesthesia may improve anesthetic safety by reducing inhalant anesthetic requirements and improving cardiovascular function during anesthesia.

Isoflurane induces expression of vascular endothelial growth factor through activating protein kinase C in myocardial cells

Objective Vascular endothelial growth factor (VEGF) plays important roles in establishing collateral circulation of ischemic myocardium. This study aimed to investigate the effect of isoflurane on VEGF expression and the potential intracellular signal transduction pathway in cultured rat myocardial cells in order to further reveal the molecular mechanism of myocardial preservation of isoflurane. Methods Primary myocardial cells of Sprague-Dawley rats were isolated and cultured. They were divided randomly into control group, isoflurane group, protein kinase C (PKC) inhibitor group and PKC inhibitor+isoflurane group where cells were respectively incubated without any treatment, treated by 0.5, 1.0 and 1.5 minimum alveolar concentration (MAC) of isoflurane for 6 hours, by PKC inhibitor calphostin C at a final concentration of 50 nmol/L and by 50 nmol/L calphostin C+1.0 MAC isoflurane for 6 hours. VEGF expression was detected by enzyme-linked immunosorbent assay (ELISA) and the expression levels of PKC isoforms were determined by Western immunoblotting method. Results Isoflurane increased the VEGF expression in myocardial cells in a dose-dependent way. VEGF levels were significantly higher in 1.0 and 1.5 MAC isoflurane groups than in the control group (both P<0.01). The effect of isoflurane on upregulating VEGF expression was blocked by PKC inhibitor calphostin C ( P<0.01), but calphostin C did not alter VEGF expression ( P>0.05). Isoflurane induced the activation and translocation of PKCɛ. Immunoblotting analysis revealed that the immunoreactivity of PKCɛ increased significantly in the membrane fractions and deceased significantly in the kytoplasm fractions for cells treated with 1.0 MAC isoflurane as compared with the untreated cells, but not of PKCα, PKCδ and PKCζ ( P<0.01). Conclusion Isoflurane induces myocardial cells to release VEGF through activating PKCɛ from the endochylema to the cytomembrane, suggesting a possible novel mechanism of isoflurane protecting myocardial cells.

The effects of urethane on the isoflurane minimum alveolar concentration in rats

Urethane is often used as a sole anaesthetic agent for non-recovery studies in laboratory animals. However, the use of urethane is controversial, in part, because the electroencephalogram after urethane administration is similar to the electroencephalogram recorded from unanaesthetized animals. Here, we assessed the minimum alveolar concentration (MAC)-sparing effects of urethane by measuring the effect of two doses of urethane on the MAC of isoflurane in male Sprague Dawley rats. Isoflurane MAC was measured before and after intravenous administration of urethane at 1.0 g/kg (Group G₁, n = 6) and 1.5 g/kg (Group G₁.₅, n = 6), or an equal volume of 0.9% saline (Group Gs, n = 6). Baseline isoflurane MAC was not statistically different between groups (isoflurane concentration: 1.47 ± 0.08%, 1.40 ± 0.19% and 1.42 ± 0.12% for G₁, G₁.₅ and Gs, respectively). Intravenous injection of saline did not alter isoflurane MAC (post-saline MAC: 1.43 ± 0.11%). After urethane administration, isoflurane MAC decreased in a dose-dependent manner (new MAC G₁: 0.19 ± 0.06%; G₁.₅: 0.03 ± 0.01%; P < 0.05). The isoflurane MAC after 1.5 g/kg urethane was not significantly different from room air isoflurane concentrations (0.01 ± 0.01%), demonstrating a 100% MAC reduction at this dose. In conclusion, high-dose urethane (1.5 g/kg intravenously) was suitable as a sole anaesthetic agent to prevent gross purposeful movement during the conditions of the study, whereas low-dose urethane (1.0 g/kg intravenously) was not.

The Effects of Intravenous Gabapentin Administration on the Minimum Alveolar Concentration of Isoflurane in Cats

Gabapentin is a structural analog of gamma-aminobutyric acid, one of the inhibitory neurotransmitters of the mammalian central nervous system. It is increasingly being used preemptively to control postoperative pain. Therefore, its interaction with inhaled anesthetics is of clinical interest. In this study, we examined the effects of gabapentin on the minimum alveolar concentration (MAC) of isoflurane in cats. We hypothesized that gabapentin would decrease the MAC of isoflurane in a dose-dependent manner. Six cats were included in the study. Gabapentin was administered IV to achieve target plasma concentrations between 0 and 16 microg/mL and the MAC of isoflurane was determined at each gabapentin concentration. Gabapentin concentrations were quantitated by liquid chromatography-mass spectrometry analysis of extracted plasma samples. MAC values at the different gabapentin plasma concentrations were analyzed by a repeated-measures analysis of variance using the Huynh-Feldt correction for violation of the sphericity assumption. Actual gabapentin concentrations were 0 + or - 0, 1.18 + or - 0.23, 2.25 + or - 0.23, 4.96 + or - 1.19, 10.63 + or - 1.37, and 19.69 + or - 3.97 microg/mL for the target concentrations of 0, 1, 2, 4, 8, and 16 microg/mL, respectively. The MAC of isoflurane in this study was 2.10% + or - 0.13%, 2.10% + or - 0.14%, 2.13% + or - 0.12%, 2.06% + or - 0.11%, 2.11% + or - 0.15%, and 2.09% + or - 0.25% at target plasma concentrations of 0, 1, 2, 4, 8, and 16 microg/mL, respectively. We conclude that gabapentin did not have a detectable effect on the MAC of isoflurane in cats.