Role of the β1-Adrenergic Pathway in Anesthetic and Ischemic Preconditioning against Myocardial Infarction in the Rabbit Heart In Vivo

Background: The early memory of anesthetic-induced preconditioning (APC) is a period when myocardial protection continues even after removal of the anesthetic. Because adenosine triphosphate-sensitive potassium (KATP) channels are important mediators of APC, the authors investigated the hypothesis that the memory involves channel priming by isoflurane via a long-term modulation of the sensitivity to intracellular adenosine nucleotides.

Methods: Ventricular cardiomyocytes were obtained from the rat hearts after 30 min in vivo APC with 1.4% isoflurane and from control non-APC rat hearts. Whole cell and excised inside-out patch clamp techniques were used to study the sarcolemmal KATP channel. Membrane expression of KATP channel proteins, the pore-forming inward rectifier Kir6.2, and the regulatory sulfonylurea receptor SUR2A were assessed in APC and non-APC hearts by Western blotting.

Results: Activation of whole cell KATP current by isoflurane was enhanced after in vivo APC. At the single-channel level, this was paralleled by a 12-fold decrease in adenosine 5'-triphosphate sensitivity and a 3-fold decrease in adenosine 5'-diphosphate sensitivity, without changing the probability of channel opening or single-channel conductance. The membrane expression of Kir6.2 and SUR2A subunits was not altered by in vivo APC. A direct in vitro application of isoflurane to excised membrane patches increased the channel open probability and produced a 4-fold decrease in adenosine 5'-triphosphate sensitivity only of channels in non-APC myocytes.     

Distinct Roles for Sarcolemmal and Mitochondrial Adenosine Triphosphate-sensitive Potassium Channels in Isoflurane-induced Protection against Oxidative Stress

Background: Cardiac preconditioning, including that induced by halogenated anesthetics, is an innate protective mechanism against ischemia-reperfusion injury. The adenosine triphosphate-sensitive potassium (KATP) channels are considered essential in preconditioning mechanism. However, it is unclear whether KATP channels are triggers initiating the preconditioning signaling, and/or effectors responsible for the cardioprotective memory and activated during ischemia-reperfusion.

Methods: Adult rat cardiomyocytes were exposed to oxidative stress with 200 [mu]m H2O2 and 100 [mu]m FeSO4. Myocyte survival was determined based on morphologic characteristics and trypan blue exclusion. To induce preconditioning, the myocytes were pretreated with isoflurane. The involvement of sarcolemmal and mitochondrial KATP channels was investigated using specific inhibitors HMR-1098 and 5-hydroxydecanoic acid. Data are expressed as mean +/- SD.

Results: Oxidative stress induced cell death in 47 +/- 14% of myocytes. Pretreatment with isoflurane attenuated this effect to 26 +/- 8%. Blockade of the sarcolemmal KATP channels abolished the protection by isoflurane pretreatment when HMR-1098 was applied throughout the experiment (50 +/- 21%) or only during oxidative stress (50 +/- 12%), but not when applied during isoflurane pretreatment (29 +/- 13%). Inhibition of the mitochondrial KATP channels abolished cardioprotection irrespective of the timing of 5-hydroxydecanoic acid application. Cell death was 42 +/- 23, 45 +/- 23, and 46 +/- 22% when 5-hydroxydecanoic acid was applied throughout the experiment, only during isoflurane pretreatment, or only during oxidative stress, respectively.     

Delayed inhibition of an anticipatory action during motion extrapolation

Background  

Continuous visual information is important for movement initiation in a variety of motor tasks. However, even in the absence of visual information people are able to initiate their responses by using motion extrapolation processes. Initiation of actions based on these cognitive processes, however, can demand more attentional resources than that required in situations in which visual information is uninterrupted. In the experiment reported we sought to determine whether the absence of visual information would affect the latency to inhibit an anticipatory action.     

Neural prediction of complex accelerations for object interception

To intercept or avoid moving objects successfully, we must compensate for the sensorimotor delays associated with visual processing and motor movement. Although straightforward in the case of constant velocity motion, it is unclear how humans compensate for accelerations, as our visual system is relatively poor at detecting changes in velocity. Work on free-falling objects suggests that we are able to predict the effects of gravity, but this represents the most simple, limiting case in which acceleration is constant and motion linear. Here, we show that an internal model also predicts the effects of complex, varying accelerations when they result from lawful interactions with the environment. Participants timed their responses with the arrival of a ball rolling within a tube of various shapes. The pattern of errors indicates that participants were able to compensate for most of the effects of the ball acceleration (～85%) within a relatively short practice (～300 trials). Errors on catch trials in which the ball velocity was unexpectedly maintained constant further confirmed that participants were expecting the effect of acceleration induced by the shape of the tube. A similar effect was obtained when the visual scene was projected upside down, indicating that the mechanism of this prediction is flexible and not confined to ecologically valid interactions. These findings demonstrate that the brain is able to predict motion on the basis of prior experience of complex interactions between an object and its environment.