Anesthesiology
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CW002 is an investigational nondepolarizing, neuromuscular blocking agent with a rapid onset and intermediate duration of action in animals. This is a single ascending dose, healthy subject study exploring tolerability, pharmacokinetics, and potency. ⋯ CW002 has predictable pharmacokinetics and is likely to have a rapid onset with an intermediate duration of action at 3× ED95. This model provides information to inform critical decisions (e.g., dose, study design) for continued development of CW002.
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Ketamine is a general anesthetic thought to act by antagonizing N-methyl-D-aspartate receptors. However, ketamine acts on multiple channels, many of which are potential targets-including hyperpolarization-activated cyclic nucleotide-gated and potassium channels. In this study we tested the hypothesis that potassium leak channels contribute to the anesthetic action of ketamine. ⋯ The results of this study show that mechanisms additional to hyperpolarization-activated cyclic nucleotide-gated channel block are likely to explain the anesthetic action of ketamine and suggest facilitatory action at two-pore potassium leak channels.
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Systemic toxicity of local anesthetics is predominantly complicated by their myocardial toxicity. Especially long-acting local anesthetics exert a negative inotropic effect that has been described at lower concentrations than defined for blockade of myocardial ion channels. We evaluated the negative inotropic effect of bupivacaine at a concentration described for clinical toxicity testing the hypothesis that negative inotropy is a result of reduced Ca sensitivity rather than blockade of ion channels. ⋯ We provide evidence that the negative inotropic effect of bupivacaine may be caused mainly by a reduction in myofilament sensitivity to Ca.
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The authors hypothesized that low tidal volume (VT) would minimize ventilator-induced lung injury regardless of the degree of mechanical power. The authors investigated the impact of power, obtained by different combinations of VT and respiratory rate (RR), on ventilator-induced lung injury in experimental mild acute respiratory distress syndrome (ARDS). ⋯ In experimental mild ARDS, even at low VT, high mechanical power promoted ventilator-induced lung injury. To minimize ventilator-induced lung injury, low VT should be combined with low power.