Mechanisms of Volatile Anesthetic-Induced Myocardial Protection

Volatile anesthetics protect myocardium against reversible and irreversible ischemic injury. Experimental evidence from several in vitro and in vivo animal models demonstrates that volatile agents enhance the recovery of stunned myocardium and reduce the size of myocardial infarction after brief or prolonged coronary artery occlusion and reperfusion, respectively. This protective effect persists after the anesthetic has been discontinued, a phenomenon known as anesthetic-induced preconditioning (APC). Recent clinical data also demonstrates evidence of APC in patients during cardiac surgery. Thus, administration of volatile anesthetics may represent a novel therapeutic approach that reduces morbidity and mortality associated with perioperative myocardial ischemia and infarction. The mechanisms responsible for APC appear to be similar to those implicated in ischemic preconditioning, but nonetheless have subtle differences. Accumulating evidence indicates that APC is characterized by complex signal transduction pathways that may include adenosine receptors, G proteins, protein kinase C, reactive oxygen species, and sarcolemmal or mitochondrial KATP channels. Opioid analgesics may further enhance APC as well. This article will review recent advances in the understanding of mechanisms responsible for volatile anesthetic-induced myocardial protection

Use of fiber optic technology to measure the effects of anesthesia on luciferase reaction kinetics

In vivo bioluminescent imaging (BLI) is a sensitive and reliable technique for studying gene expression, although experiments must be controlled tightly to obtain reproducible and quantitative measurements. The luciferase reaction depends on the availability of the reaction substrate, oxygen, and ATP, the distribution of which can vary markedly in different tissues. Here we used in vivo fiber optic technology, combined with stereotaxis-assisted surgery, to assess luciferase reaction kinetics in response to 2 anesthetic regimens, isoflurane and ketamine–xylazine. Transgenic rats that expressed luciferase under the control of the human prolactin promoter were used as a model organism. Anesthesia had a marked effect on luciferase reaction kinetics. The rise time to peak emission differed by 20 min between isoflurane and ketamine–xylazine. Optical imaging using a charge-coupled–device camera confirmed this delay. These results demonstrate that different anesthetics can have substantial effects on luciferase reaction kinetics and suggest that the timing of image acquisition after substrate injection should be optimized in regard to experimental conditions and the tissues of interest

Tuning the Clock: Uranium and Thorium Chronometers Applied to CS 31082-001

We obtain age estimates for the progenitor(s) of the extremely metal-poor ([Fe/H = -2.9) halo star CS 31082-001, based on the recently reported first observation of a Uranium abundance in this (or any other) star. Age estimates are derived by application of the classical r-process model with updated nuclear physics inputs. The [U/Th] ratio yields an age of 13+-4 Gyr or 8+-4 Gyr, based on the use of the ETFSI-Q or the new HFBCS-1 nuclear mass models, respectively. Implications for Thorium chronometers are discussed.Comment: 5 pages incl. 1 figure, a shorter 3 page version will be published in the proceedings of the "Astrophysical Ages and Timescales" conference held in Hilo, Hawaii, Feb 5-9, 200

Critical Behavior of Random Bond Potts Models

The effect of quenched impurities on systems which undergo first-order phase transitions is studied within the framework of the q-state Potts model. For large q a mapping to the random field Ising model is introduced which provides a simple physical explanation of the absence of any latent heat in 2D, and suggests that in higher dimensions such systems should exhibit a tricritical point with a correlation length exponent related to the exponents of the random field model by \nu = \nu_RF / (2 - \alpha_RF - \beta_RF). In 2D we analyze the model using finite-size scaling and conformal invariance, and find a continuous transition with a magnetic exponent \beta / \nu which varies continuously with q, and a weakly varying correlation length exponent \nu \approx 1. We find strong evidence for the multiscaling of the correlation functions as expected for such random systems.Comment: 13 pages, RevTeX. 4 figures included. Submitted to Phys.Rev.Let

Mechanism of Preconditioning by Isoflurane in Rabbits: A Direct Role for Reactive Oxygen Species

LARGE quantities of reactive oxygen species (ROS) released during reperfusion after coronary artery occlusion damage proteins responsible for intracellular homeostasis, produce tissue injury, depress contractile function, and increase myocardial infarct size. In contrast, small quantities of ROS may exert beneficial effects during ischemia and reperfusion when released before a prolonged ischemic event. ROS derived from mitochondria during a brief ischemic episode produce preconditioning. Free radical scavengers administered during ischemic preconditioning (IPC) markedly attenuate the protective effect of the preconditioning stimulus on infarct size. These data suggest that IPC is mediated in part by small quantities of ROS released during preconditioning. Volatile anesthetics protect myocardium against infarction through a signal transduction pathway that includes adenosine type 1 receptors, protein kinase C, inhibitory guanine regulatory proteins, and mitochondrial and sarcolemmal adenosine triphosphate-regulated potassium (KATP) channels. A recent investigation by Müllenheim et al . provides compelling evidence that ROS also mediate myocardial protection produced by volatile anesthetics. We sought to confirm and extend these important results by examining the hypothesis that ROS scavengers inhibit isoflurane-induced protection against irreversible ischemic injury. We further tested the hypothesis that isoflurane directly generates ROS in rabbit ventricular myocardium in vivo using a confocal microscopic technique combined with the superoxide anion-specific fluorescent probe dihydroethidium

Target Zones in History and Theory: Lessons from an Austro-Hungarian Experiment (1896-1914)

The first known experiment with an exchange rate band took place in Austria- Hungary between 1896 and 1914. The rationale for introducing this policy rested on precisely those intuitions that the modern literature has emphasized: the band was designed to secure both exchange rate stability and monetary policy autonomy. However, unlike more recent experiences, such as the ERM, this policy was not undermined by credibility problems. The episode provides an ideal testing ground for some important ideas in modern macroeconomics: specifically, can formal rules, when faithfully adhered to, provide policy makers with some advantages such as short term autonomy? First, we find that a credible band has a "microeconomic" influence on exchange rate stability. By reducing uncertainty, a credible fluctuation band improves the quality of expectations, a channel that has been neglected in the modern literature. Second, we show that the standard test of the basic target zone model is flawed and develop an alternative methodology. We believe that these findings shed a new light on the economics of exchange rate bands

Thermal Equilibrium Curves and Turbulent Mixing in Keplerian Accretion Disks

We consider vertical heat transport in Keplerian accretion disks, including the effects of radiation, convection, and turbulent mixing driven by the Balbus-Hawley instability, in astronomical systems ranging from dwarf novae (DNe), and soft X-ray transients (SXTs), to active galactic nuclei (AGN). We propose a modified, anisotropic form of mixing-length theory, which includes radiative and turbulent damping. We also include turbulent heat transport, which acts everywhere within disks, regardless of whether or not they are stably stratified, and can move entropy in either direction. We have generated a series of vertical structure models and thermal equilibrium curves using the scaling law for the viscosity parameter $\alpha$ suggested by the exponential decay of the X-ray luminosity in SXTs. We have also included equilibrium curves for DNe using an $\alpha$ which is constant down to a small magnetic Reynolds number ($\sim 10^4$). Our models indicate that weak convection is usually eliminated by turbulent radial mixing. The substitution of turbulent heat transport for convection is more important on the unstable branches of thermal equilibrium S-curves when $\alpha$ is larger. The low temperature turnover points $\Sigma_{max}$ on the equilibrium S-curves are significantly reduced by turbulent mixing in DNe and SXT disks. However, in AGN disks the standard mixing-length theory for convection is still a useful approximation when we use the scaling law for $\alpha$, since these disks are very thin at the relevant radii. In accordance with previous work, we find that constant $\alpha$ models give almost vertical S-curves in the $\Sigma-T$ plane and consequently imply very slow, possibly oscillating, cooling waves.Comment: 43 pages, 12 figures, 6 tables, to be published in Ap