Background: Mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels play a pivotal role in mediating cardiac preconditioning. The effects of intravenous anesthetics on this protective channel have not been investigated so far, but would be of importance with respect to experimental as well as clinical medicine.
Methods: Live cell microscopy was used to visualize and measure autofluorescence of flavoproteins, a direct reporter of mitoKATP channel activity, in response to the direct and highly selective mitoKATP channel opener diazoxide, or to diazoxide following exposure to various anesthetics commonly used in experimental and clinical medicine. A cellular model of ischemia with subsequent hypoosmolar trypan blue staining served to substantiate the effects of the anesthetics on mitoKATP channels with respect to myocyte viability.
Results: Diazoxide-induced mitoKATP channel opening was significantly inhibited by the anesthetics R-ketamine, and the barbiturates thiopental and pentobarbital. Conversely, urethane, 2,2,2-trichloroethanol (main metabolite of [alpha]-chloralose and chloral hydrate), and the opioid fentanyl potentiated the channel-opening effect of diazoxide, which was abrogated by coadministration of chelerythrine, a specific protein kinase C inhibitor. S-ketamine, propofol, xylazine, midazolam, and etomidate did not affect mitoKATP channel activity. The significance of these modulatory effects of the anesthetics on mitoKATP channel activity was substantiated in a cellular model of simulated ischemia, where diazoxide-induced cell protection was mitigated by R-ketamine and the barbiturates, while urethane, 2,2,2-trichloroethanol, and fentanyl potentiated myocyte protection. 相似文献
Objective To investigate effects of different rewarming rates and maintenance of light hypothermia on inflammatory response in rabbits after limb blast injury, coupled with seawater immersion. Methods First, the model of limb blast injury coupled with seawater immersion was reproduced [the animals were immersed to low body temperature of (31.0±0.5℃)]. Then, 24 adult rabbits were randomly divided into group Ⅰ [the rapid rewarming group, n=6, rewarmed to (38±0.5)℃ at a rate of (8.94±0.93)℃/h], group Ⅱ [the slow rewarming group, n=6, rewarmed to (38±0.5)℃ at a rate of (3.88±0.22)℃/h], group Ⅲ [another slow rewarming group, n=6, rewarmed to (38±0.5)℃ at a rate of (2.18±0.12)℃/h], and the H group [the hypothermia group, n =6, rewarmed to (34 - 35)℃ at a rate of (4.49±0.66)℃/h and kept at that temperature till termination of the experiment]. Regulation of ambient temperature and warm transfusion were used to restore body temperature to target levels and maintained there for 6 hours. Blood samples were taken at 5 different times, I.e. Pre-injury time(T0), post-immersion time (T1), the time when rewarming started (T2), 3 h after rewarming (T3), and 6 h after rewarming (T4). Tissue samples from heart, liver, intestinum, lung and kidney were also collected. Levels of TNF-α (tumor necrosis factor-α), IL-1β (interleukin-1β) and IL-6 (interleukin-6) in plasma and MPO (myeloperoxidase) in homogenate were detected. Results Following rewarming, TNF-α, IL-1β, IL-6 concentrations in the plasma of the animals in group Ⅰ and group H were significantly higher when compared with those of the animals in group Ⅱ and group Ⅲ (P<0.05, P<0.01), and MPO activity in homogenate was significantly higher when compared with that of the animals in group Ⅱ and group Ⅲ(P<0.01, P<0.05), and no statistical difference could be seen between group Ⅱ and Ⅲ (P>0.05). Conclusions Rapid rewarming and maintenance of light hypothermia could obviously elevate TNF-α, IL-1β, IL-6 concentrations in plasma and MPO activity in homogenate, following limb blast injury coupled with hypothermia induced by seawater immersion, while slow rewarming (with a rewarming rate of 2-4℃/h) could significantly inhibit TNF-α, IL-1β, IL-6 levels and PMN activity. 相似文献