46 research outputs found

    Comparing responses to a noxious stimulus in rats exposed to Dex alone with rats administered Dex and a low dose of either sevoflurane or propofol.

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    A noxious stimulus was applied at different time points in an experiment. Responses were tabulated and are presented numerically in the table. Statistical difference is calculated with Fisher’s exact test. A, data from female rats. B, data from male rats. (TIF)</p

    Female rats exposed to Dex supplemented with a low dose of propofol exhibited slowed heart and respiration rates while blood oxygen saturation levels were unaffected.

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    The vital signs were measured at various times during the experiment. The first measurement (“1.7% isoflurane”) took place while the rats were receiving 1.7% isoflurane, prior to Dex administration. The second measurement (“1.1% isoflurane”) was taken while the rats were receiving 1.1% isoflurane, prior to Dex administration. The third measurement (“End of Bolus”) was taken immediately after the bolus of Dex was administered. The 1.1% isoflurane was turned off but not yet washed out. Rats were breathing O2/Air. The fourth measurement (“t = 15”) was taken fifteen minutes after the end of the bolus. All isoflurane should have been washed out since rats had been breathing O2/Air for 15 minutes. The fifth, sixth and seventh measurements (“t = 30”, “t = 45”, “t = 60”) were taken thirty, forty-five and sixty minutes after the end of the bolus. Statistics: A one-way repeated measures ANOVA was performed to compare the effects of Dex at different time points with that before Dex application. Tukey’s HSD Test for Multiple Comparisons found that the mean values for HR were significantly different in the presence and absence of Dex. Comparisons of HR: 1.7% isoflurane vs. 1.1% isoflurane, p = 0.44: We compared the HR at 1.1% isoflurane to the rest of the time points, 1.1% isoflurane vs. End of Bolus, p 2: 1.7% isoflurane vs. 1.1% isoflurane, p = 0.95: We compared the HR at 1.1% isoflurane to the rest of the time points, 1.1% isoflurane vs. t = 15, p <0.06: 1.1% isoflurane vs. t = 30, p = 0.41: 1.1% isoflurane vs. t = 45, p = 0.43: 1.1% isoflurane vs. t = 60, p = 0.28.</p

    The combination of atipamezole and caffeine dramatically accelerated emergence from anesthesia produced by Dex alone or from the combinations of Dex with Sevoflurane or Dex with Propofol, in male rats.

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    The same group of 8 rats were exposed to three sedation sessions, a week apart. At the end of each session the rats received a bolus injection of atipamezole (10 μg/kg) and caffeine (25 mg/kg). Rats were placed on their backs in a waking box, and the time for the rats to recover their righting reflex was recorded. Data (RORR Times in seconds): Dex alone—5, 9, 5, 1, 29, 1, 15, 2, Dex with Sevoflurane—110, 72, 81, 59, 62, 32, 85, 59, Dex with Propofol—222, 182, 150, 44, 32, 59, 129, 25. (TIF)</p

    Determining the dose of propofol required to maintain unconsciousness to define a low dose of the drug.

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    For this experiment a group of rats received a bolus of 5 mg/kg of propofol, applied in 5 minutes via a pump, after which they received a continuous infusion of propofol, at different concentrations for an additional 60 minutes. All rats remained unconscious for the 60-minute infusion if the infusion rates of propofol were kept at or above 400 ÎĽg/kg/min. In contrast, 300 ÎĽg/kg/min was not sufficient to keep the rats unconscious during the infusion. (TIF)</p

    A—determining the concentration of sevoflurane required to prevent half of the responses to a noxious mechanical stimulus.

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    Details about the stimulus are in the Methods. The green column represents ~1 MAC equivalence concentration or EC50. (TIF)</p

    The ARRIVE guidelines 2.0: Author checklist.

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    Clinically useful anesthetics are associated with delirium and cognitive decline in the elderly. Dexmedetomidine (Dex), an α2 adrenergic receptor agonist, is an intravenous sedative with analgesic properties. Dex is associated with a lower incidence of delirium in the elderly. In this study, we first assessed whether a high dose of Dex alone was a clinically useful anesthetic. Finding that it was not, we sought to determine whether supplementation of Dex with low doses of two common anesthetics, propofol or sevoflurane, created an effective general anesthetic. Rats were sedated with a bolus followed by a continuous infusion of Dex and a low dose of a second agent—propofol, or sevoflurane. A strong noxious stimulus was applied every 15 minutes while monitoring vital signs. A combination of the α2 competitive antagonist, atipamezole, and caffeine was administered to reverse the anesthesia. Abdominal surgery was used to validate the efficacy of these dosing regimens. The animals responded to noxious stimuli when receiving Dex alone. Supplementing Dex with either a low dose of propofol or sevoflurane completely suppressed responses to the noxious stimulus and allowed the rats to tolerate abdominal surgery with complete immobility and no alterations in vital signs, suggesting that the drug combinations were effective anesthetics. EEG recordings showed suppression of high frequency activity suggesting that awareness and memory were impaired. Previously we found that combination of atipamezole and caffeine rapidly and completely reversed the sedation and bradycardia elicited by Dex. In this study, atipamezole and caffeine accelerated the time to emergence from unconsciousness by >95% in Dex supplemented with either propofol or sevoflurane.In conclusionOur results suggest that Dex supplemented with a low dose of a second agent creates a potent anesthetic that is rapidly reversed by atipamezole and caffeine.</div

    Experimental protocol.

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    For this protocol, a 5-minute infusion of a bolus of Dex (10 ÎĽg/kg) was followed by 60 minutes of a maintenance infusion of Dex (10 ÎĽg/kg/hr), left panel. The same rats were exposed to a similar protocol, but one where a second agent supplemented the Dex, either propofol or sevoflurane, right panel. The second agent was present for the entire Dex infusion. At various times, the rats were tested with a tail clamp to measure immobility. Vital signs were obtained throughout the experiment. At the end of the protocol, rats received an injection of either saline or atipamezole with caffeine (randomized order). Rats were then placed on their backs in a waking box, and the time for the rats to recover their righting reflex was recorded. This time is plotted in the subsequent Figs as the emergence time.</p

    The combination of atipamezole and caffeine dramatically accelerated emergence from the anesthesia produced by Dex supplemented with a low dose of sevoflurane.

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    The same group of 8 rats were exposed to two sedation sessions, a week apart. In one anesthesia session the rats received Dex alone while in the second session the rats received Dex and sevoflurane (see Results for details). The order of the sessions was randomized. At the end of both sessions the rats received a bolus injection of atipamezole (10 μg/kg) and caffeine (25 mg/kg). Emergence from anesthesia was fast in both cases, but Dex alone was significantly faster. The difference was significant (p < 0.0001), two tailed paired T-test, t = 7.93 and df = 7). Plotted are each data point, the mean value ± standard deviation.</p

    The combination of atipamezole and caffeine dramatically accelerated emergence from the anesthesia produced by Dex supplemented with a low dose of propofol.

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    The same group of 8 rats were exposed to two anesthesia sessions, a week apart. At the end of one session the rats received a bolus injection of saline and in the other atipamezole (20 μg/kg) and caffeine (25 mg/kg). The order of the drug injections was randomized. Rats were placed on their backs in a waking box, and the time for the rats to recover their righting reflex was recorded. This time is plotted in the Fig as the Emergence Time. The Fig plots the time to emerge from anesthesia for rats receiving saline (leftmost group) or the same rats receiving atipamezole and caffeine (rightmost group). There was ~95% decrease in Emergence Time. The difference was significant (p < 0.0001, two tailed paired T-test, t = 11.89 and df = 7). Plotted are each data point, the mean value ± standard deviation.</p
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